Disorders of amino acid metabolism in children. Protein metabolism disorders

This is the largest group of hereditary metabolic diseases. Almost all of them are inherited in an autosomal recessive manner. The cause of diseases is the deficiency of one or another enzyme responsible for the synthesis of amino acids. The disease is accompanied by vomiting and dehydration, lethargy or agitation and convulsions. IN late age mental decline manifests itself and physical development.

Hereditary diseases with impaired amino acid metabolism include phenylketonuria, albinism, etc.

Phenylketonuria (PKU) was first described by A. Fehling in 1934. In patients, the conversion of the amino acid phenylalanine into tyrosine is impaired due to a sharp decrease in the activity of the enzyme phenylalanine hydroxylase. As a result, the content of phenylalanine in the blood and urine of patients increases significantly. Next, phenylalanine is converted into phenylpyruvic acid, which is a neurotropic poison and disrupts the formation of the myelin sheath around the axons of the central nervous system.

Phenylketonuria occurs on average worldwide with a frequency of 1 in 1000 births. However, there are significant differences between populations in this indicator: 1:2600 in Turkey, 1:4500 in Ireland, 1:30,000 in Sweden, 1:119,000 in Japan. The frequency of heterozygous carriage in most European populations is 1:100.

The (phenylhydroxylase) locus is located in long shoulder 12th chromosome. Currently, molecular genetic diagnosis and identification of heterozygous carriage are possible for most families. The disease is inherited in an autosomal dominant manner. There are several forms of phenylketonuria, which differ in the severity of the disease. This is due to the presence of 4 alleles of the gene and their combinations.

A child with phenylketonuria is born healthy, but in the very first weeks, due to the intake of phenylalanine in the body through mother’s milk, increased excitability, convulsive syndrome, and a tendency to dermatitis develop; the urine and sweat of patients have a characteristic “mouse” smell, but the main symptoms of PKU are seizures and mental retardation.

Most patients are blond with fair skin and blue eyes, which is determined by insufficient synthesis of the melanin pigment. The diagnosis of the disease is established on the basis of clinical data and the results of a biochemical analysis of urine (for phenylpyruvic acid) and blood (for phenylalanine). For this purpose, a few drops of blood on filter paper are subjected to chromatography and the phenylalanine content is determined. Sometimes the Felling test is used - 10 drops of a 5% solution of ferric chloride and acetic acid are added to 2.5 ml of fresh urine of a child. The appearance of a blue-green color indicates the presence of the disease.

The treatment of phenylketonuria is now well developed. It consists of prescribing a diet to the patient (vegetables, fruits, jam, honey) and specially processed protein hydrolysates with low content phenylalanine (lofelac, ketonyl, minafen, etc.). Prenatal diagnostic methods have now been developed. Early diagnosis and preventive treatment prevent the development of the disease.

Albinism (oculocutaneous) described in 1959. The disease is caused by the lack of synthesis of the enzyme tyrosinase. It is characterized by discoloration of the skin, hair, eyes, regardless of race and age. The skin of patients is pink-red and does not tan at all. Has a predisposition to malignant neoplasms. Hair is white or yellowish. The iris is gray-blue in color, but may also be pinkish due to the reflection of light from the fundus of the eye. Patients are characterized by severe photophobia, their vision is reduced and does not improve with age.

Albinism occurs with a frequency of 1 in 39,000 and is inherited in an autosomal recessive manner. The gene is localized on the long arm of chromosome 11.

Hereditary diseasesrelated to violation

carbohydrate metabolism

It is known that carbohydrates are part of a number of biologically active substances - hormones, enzymes, mucopolysaccharides, which perform energy and structural functions. As a result of impaired carbohydrate metabolism, glycogen storage disease, galactosemia, etc. develop.

Glycogen storage disease associated with a violation of the synthesis and decomposition of glycogen - animal starch. Glycogen is formed from glucose during fasting; Normally, it turns back into glucose and is absorbed by the body. When these processes are disrupted, a person develops serious diseases - various types of glycogenosis. These include Gierke's disease, Pompe disease, etc.

Glycogenosis (type I - Gierke's disease). In patients, large amounts of glycogen accumulate in the liver, kidneys and intestinal mucosa. Its conversion into glucose does not occur, because the enzyme gluco-6-phosphatase, which regulates blood glucose levels, is missing. As a result, the patient develops hypoglycemia, and glycogen accumulates in the liver, kidneys and intestinal mucosa. Gierke's disease is inherited in an autosomal recessive manner.

Immediately after birth, the main symptoms of the disease are glycemic seizures and hepatomegaly (enlarged liver). From the 1st year of life, growth retardation is noted. The patient's appearance is characteristic: a large head, a “doll face,” a short neck, and a protruding stomach. In addition, nosebleeds, delayed physical and sexual development, and muscle hypotension are noted. The intelligence is normal. The level of uric acid in the blood rises, so gout can develop with age.

Diet therapy is used as treatment: frequent meals, increased carbohydrate content and limited fat in the diet.

Glycogenosis (type II - Pompe disease) occurs in a more severe form. Glycogen accumulates both in the liver and in skeletal muscles, myocardium, lungs, spleen, adrenal glands, vascular walls, and neurons.

In newborns, after 1-2 months, muscle weakness appears, deficiency of 1,4-glucosidase in the liver and muscles. During the same period, cardiomegaly (enlargement of the heart) and macroglossia (pathological enlargement of the tongue) occur. Often, patients develop a severe form of pneumonia due to the accumulation of secretions in the respiratory tract. Children die in the first year of life.

The disease is inherited in an autosomal recessive manner. The gene is localized on the long arm of chromosome 17. Diagnosis of the disease is possible even before the birth of the child. For this purpose, the activity of the enzyme 1,4-glucosidase is determined in amniotic fluid and its cells.

Galactosemia. With this disease, galactose accumulates in the patient’s blood, which leads to damage to many organs: the liver, nervous system, eyes, etc. Symptoms of the disease appear in newborns after drinking milk, since galactose is a component of the milk sugar lactose. The hydrolysis of lactose produces glucose and galactose. The latter is necessary for the myelination of nerve fibers. When there is an excess of galactose in the body, it is normally converted into glucose using the enzyme galactose-1-phosphate-uridyltransferase. When the activity of this enzyme decreases, galactose-1-phosphate accumulates, which is toxic to the liver, brain, and eye lens.

The disease manifests itself from the first days of life with digestive disorders and intoxication (diarrhea, vomiting, dehydration). In patients, the liver enlarges, liver failure and jaundice develop. Cataracts (clouding of the lens of the eye) and mental retardation are detected. In children who died in the first year of life, cirrhosis of the liver was discovered at autopsy.

The most accurate methods for diagnosing galactosemia are to determine the activity of the enzyme galactose-1-phosphate-uridyltransferase in red blood cells, as well as galactose in the blood and urine, where its levels are increased. If milk (a source of galactose) is excluded from the diet and the diet is started early, sick children can develop normally.

The type of inheritance of galactosemia is autosomal recessive. The gene is localized on the short arm of chromosome 9. The disease occurs with a frequency of 1 in 16,000 newborns.

Hereditary diseases associated with the disorder

lipid metabolism

Hereditary diseases of lipid metabolism (lipidoses) are divided into two main types:

1) intracellular, in which lipids accumulate in the cells of various tissues;

2) diseases with impaired metabolism of lipoproteins contained in the blood.

The most studied hereditary diseases of lipid metabolism of the first type include Gaucher disease, Niemann-Pick disease and amaurotic idiocy (Tay-Sachs disease).

Gaucher disease characterized by the accumulation of cerebrosides in the cells of the nervous and reticuloendothelial system, caused by a deficiency of the enzyme glucocerebrosidase. This leads to the accumulation of glucocerebroside in the cells of the reticuloendothelial system. In the cells of the brain, liver, lymph nodes large Gaucher cells are found. The accumulation of cerebroside in the cells of the nervous system leads to their destruction.

There are childhood and juvenile forms of the disease. Children's disease manifests itself in the first months of life with delayed mental and physical development, enlargement of the abdomen, liver and spleen, difficulty swallowing, and spasm of the larynx. Respiratory failure, infiltration (thickening of the lungs by Gaucher cells) and convulsions are possible. Death occurs in the first year of life.

The most common form of Gaucher disease is the juvenile form. It affects children of all ages and is chronic. The disease usually appears in the first year of life. Skin pigmentation (brown spots), osteoporosis (decreased bone density), fractures, and bone deformation occur. The tissues of the brain, liver, spleen, and bone marrow contain large amounts of glucocerebrosides. In leukocytes, liver and spleen cells, glucosidase activity is reduced. The type of inheritance is autosomal recessive. The gene is localized on the long arm of chromosome 1.

Niemann-Pick disease caused by a decrease in the activity of the enzyme sphingomyelinase. As a result, sphingomyelin accumulates in the liver cells, spleen, brain, and reticuloendothelial system. Due to the degeneration of nerve cells, the activity of the nervous system is disrupted.

There are several forms of the disease that differ clinically (time of onset, course and severity of neurological manifestations). However, there are also symptoms common to all forms.

The disease often manifests itself at an early age. The child's lymph nodes, abdomen, liver and spleen are enlarged; Vomiting, refusal to eat, muscle weakness, decreased hearing and vision are noted. In 20-30% of children, a cherry-colored spot is found on the retina of the eye (the “cherry pit” symptom). Damage to the nervous system leads to delayed neuropsychic development, deafness, and blindness. Resistance to infectious diseases decreases sharply. Children die at an early age. Inheritance of the disease is autosomal recessive.

Diagnosis of Niemann-Pick disease is based on the detection of increased levels of sphingomyelin in the blood plasma and cerebrospinal fluid. In the peripheral blood, large granular foam cells of Pick are detected. Treatment is symptomatic.

Amaurotic idiocy (disease Tay-Sachs) also refers to diseases associated with lipid metabolism disorders. It is characterized by the deposition of ganglioside lipid in the cells of the brain, liver, spleen and other organs. The reason is a decrease in the activity of the enzyme hexosaminidase A in the body. As a result, the axons of nerve cells are destroyed.

The disease manifests itself in the first months of life. The child becomes lethargic, inactive, and indifferent to others. Delay mental development leads to a decrease in intelligence to the point of idiocy. There is muscle hypotonia, cramps, and a characteristic “cherry pit” symptom on the retina. By the end of the first year of life, blindness occurs. Cause: atrophy optic nerves. Later, complete immobility develops. Death occurs at 3-4 years. The type of inheritance of the disease is autosomal recessive. The gene is localized on the long arm of chromosome 15.

Hereditary diseasesconnective tissue

Connective tissue in the body performs supporting, trophic and protective functions. The complex structure of connective tissue is determined genetically. Pathology in its system is the cause of various hereditary diseases and is caused, to one degree or another, by disturbances in the structure of structural proteins - collagens.

Most connective tissue diseases are associated with defects of the musculoskeletal system and skin. These include Marfan syndrome and mucopolysaccharidoses.

Marfan syndrome is one of the hereditary metabolic diseases and is characterized by systemic damage to connective tissue. It is inherited in an autosomal dominant manner with high penetrance and varying degrees of expressivity. This is associated with significant clinical and age-related polymorphism. The syndrome was first described by V. Marfan in 1886. The cause of the disease is a mutation in the gene responsible for the synthesis of the protein of connective tissue fibers, fibrillin. Blocking its synthesis leads to increased extensibility of connective tissue.

Patients with Marfan syndrome are distinguished by tall stature, long fingers, chest deformity (funnel-shaped, keeled, flattened), and flat feet. Often there are femoral and inguinal hernias, hypoplasia (underdevelopment) of muscles, muscle hypotonia, blurred vision, changes in the shape and size of the lens, myopia (up to retinal detachment), heterochromia (different coloring of areas of the iris); lens subluxation, cataract, strabismus.

In addition to the above, Marfan syndrome is characterized by congenital heart defects, dilatation of the aorta with the development of an aneurysm. Often there are respiratory disorders, lesions gastrointestinal tract and urinary system.

Treatment is mainly symptomatic. Massage, physical therapy, and in some cases surgical intervention have a positive effect. Early diagnosis of the disease is of great importance. The frequency of Marfan syndrome in the population is 1:10,000 (1:15,000).

US President Abraham Lincoln and the great Italian violinist and composer Nicolo Paganini suffered from Marfan syndrome.

Mucopolysaccharidoses represented by a whole group of hereditary diseases connective tissue. They are characterized by a violation of the metabolism of acid glycosaminoglycans in the body, which is associated with a deficiency of lysosomal enzymes. As a result, pathological metabolic products are deposited in the connective tissue, liver, spleen, cornea and cells of the central nervous system. The first information about mucopolysaccharidoses appeared in 1900, and then in 1917-1919.

Mucopolysaccharidoses affect the musculoskeletal system, internal organs, eyes, and nervous system. Clinical signs of the disease are: slower growth, short neck and torso, bone deformation, decreased intelligence, coarse facial features with large lips and tongue, umbilical and inguinal hernias, heart defects, impaired mental development with a lag from the norm.

The type of inheritance of the disease is autosomal recessive. The gene is mapped to the short arm of chromosome 4.

In total, there are 8 main types of mucopolysaccharidoses, depending on the decrease in the activity of various enzymes and the characteristics of clinical signs. To determine the type of disease, the biochemical parameters of acid glycosaminoglucans in the blood and urine of patients are examined.

Treatment: diet therapy, physiotherapy (electrophoresis, magnetotherapy, massage, physical therapy, etc.), hormonal and cardiovascular medications.

Hereditary disordersexchange in red blood cells

Hemolytic anemia include diseases caused by a decrease in hemoglobin levels and a shortening of the lifespan of red blood cells. In addition, the cause of the disease may be:

Damage to the red blood cell membrane.

Violation of the activity of erythrocyte enzymes (enzymes, glycolysis of the pentose phosphate cycle, etc.).

Violation of the structure or synthesis of hemoglobin.

The most common form of hereditary hemolytic anemia in humans is hereditary microspherocytosis. - hemolytic anemia Minkow Ski-Shoffar. The disease was described in 1900. In approximately half of cases it occurs in newborns. The diagnosis is made at the age of 3-10 years. The disease is caused by genetic abnormalities of red blood cells and is associated with congenital deficiency of lipids in their membrane. As a result of increased membrane permeability, sodium ions enter the cell and ATP is lost. Red blood cells take on a spherical shape. The altered red blood cells are destroyed in the spleen with the formation of a toxic protein - bilirubin.

With this disease, jaundice, anemia, splenomegaly (rupture of the spleen), and skeletal changes are noted. The disease can occur in two forms - chronic and acute, in which hemolysis increases, causing anemia.

Children in the first months of life often experience “ kernicterus" The reason is damage to the nuclei of the brain due to the high content of bilirubin. At an older age, high levels of bilirubin lead to the formation of stones and the development of cholelithiasis.

Patients are characterized by an enlarged spleen and liver, skeletal deformation, and abnormal alignment of teeth.

Type of inheritance - autosomal dominant with no full penetrance. The gene is mapped to the short arm of chromosome 8.

Hereditary anomaliescirculating proteins.Hemoglobinopathies- these are diseases associated with a hereditary disorder of hemoglobin synthesis. There are quantitative (structural) and qualitative forms. The former are characterized by changes in the primary structure of hemoglobin proteins, which can lead to disruption of its stability and function. In high-quality forms, the structure of hemoglobin remains normal, only the rate of synthesis of globin chains is reduced.

Thalassemia. This pathology is caused by a decrease in the rate of synthesis of polypeptide chains of normal hemoglobin A. The disease was first described in 1925. Its name comes from the Greek “Talas” - Mediterranean Sea. It is believed that the origin of most thalassemia gene carriers is associated with the Mediterranean region.

Thalassemia occurs in homo- and heterozygous forms. According to the clinical picture, it is customary to distinguish between large, intermediate, small and minimal forms. Let's focus on one of them.

Homozygous (large) thalasse Mia, aka Cooley's anemia caused by a sharp decrease in the formation of hemoglobin HbA 1 and an increase in the amount of hemoglobin F.

Clinically, the disease manifests itself towards the end of the child’s first year of life. It is characterized by a Mongoloid face, a tower type of skull, and retarded physical development. With this pathology, target-shaped erythrocytes with a low HB content, shortened life expectancy and increased osmotic resistance are found in the patient’s blood. Patients have an enlarged spleen and, less commonly, liver.

Depending on the severity of the disease, there are several forms of thalassemia. Severe thalassemia ends in rapid death in the first months of a child’s life. In chronic cases, sick children live up to 5-8 years, and in mild forms, patients live until adulthood.

Sickle cell anemia - the most common hereditary disease caused by a change in the structure of the hemoglobin molecule. People with sickle cell disease usually die before reaching adulthood. Under conditions of low partial pressure of oxygen, their red blood cells take on a sickle shape. The patient's parents' red blood cells have a slightly altered shape, but they do not suffer from anemia.

This disease was first discovered in 1910 by J. Herrick in a student who suffered from severe anemia. In the patient's blood, he identified red blood cells of an unusual sickle shape.

In 1946, Nobel laureate L. Pauling and colleagues conducted a biochemical and genetic analysis of hemoglobin from sick and healthy people and showed that hemoglobins of normal and sickle cell erythrocytes differ in mobility in an electric field and solubility. It turned out that the hemoglobin in people with sickle cell traits is a mixture of equal amounts of both normal and mutant hemoglobin. It became clear that the mutation that causes sickle cell anemia is associated with a change in the chemical structure of hemoglobin. Further studies showed that in the case of sickle cell anemia, glutamic acid is replaced by valine in the sixth nucleotide pair of the gene encoding the beta chain of human hemoglobin. In heterozygotes, altered hemoglobin is 20-45%, in homozygotes - 60-99% of total hemoglobin.

With this pathology, pale skin and mucous membranes and jaundice are noted. 60% of children have an enlarged liver. There are also murmurs in the heart area, etc. The disease occurs in the form of alternating crises and remissions.

There are no special treatment methods. It is important to protect the patient from exposure to factors that provoke the development of the disease (hypoxia, dehydration, cold, etc.).

Human chromosomal diseases

Chromosomal diseases are large group congenital hereditary diseases with multiple congenital malformations. They are based on chromosomal or genomic mutations. These two different types of mutations are collectively called “chromosomal abnormalities” for short.

The identification of at least three chromosomal diseases as clinical syndromes of congenital developmental disorders was made before their chromosomal nature was established.

The most common disease, trisomy 21, was clinically described in 1866 by the English pediatrician L. Down and was called “Down syndrome.” Subsequently, the cause of the syndrome was repeatedly subjected to genetic analysis. Suggestions have been made about a dominant mutation, a congenital infection, or a chromosomal nature.

The first clinical description of X-chromosome monosomy syndrome as a separate form of the disease was made by the Russian clinician N.A. Shereshevsky in 1925, and in 1938. G. Turner also described this syndrome. Based on the names of these scientists, monosomy on the X chromosome is called Shereshevsky-Turner syndrome.

Anomalies in the sex chromosome system in men (trisomy XXY) were first described as a clinical syndrome by G. Klinefelter in 1942. The listed diseases became the object of the first clinical and cytogenetic studies conducted in 1959.

The etiological factors of chromosomal pathology are all types of chromosomal mutations and some genomic mutations. Although genomic mutations in the animal and plant world are diverse, only 3 types of genomic mutations are found in humans: tetraploidy, triploidy and aneuploidy. Of all the variants of aneuploidy, only trisomy for autosomes, polysomy for sex chromosomes (tri-, tetra- and pentasomy) are found, and of monosomy, only monosomy X is found.

As for chromosomal mutations, all types of them have been found in humans (deletions, duplications, inversions, translocations). Chromosomal diseases include diseases caused by genomic mutations or structural changes in individual chromosomes.

The classification of chromosomal pathology is based on 3 principles that make it possible to accurately characterize the form of chromosomal pathology.

The first principle is etiological - characteristic of chromosomal or genomic mutations (triploidy, simple trisomy on chromosome 21, partial monosomy, etc.) taking into account a specific chromosome. For each form of chromosomal pathology, it is established which structure is involved in pathological process(chromosome, segment) and what the genetic disorder is (lack or excess of chromosomal material). Differentiation of chromosomal pathology based on the clinical picture is not significant, since different chromosomal abnormalities characterized by a large commonality of developmental disorders.

Second principle - determination of the type of cells in which it arose la mutation (in gametes or zygote). Gametic mutations lead to complete forms of chromosomal diseases. In such individuals, all cells carry a chromosomal abnormality inherited from the gamete. If a chromosomal abnormality occurs in the zygote or in the early stages of cleavage (such mutations are called somatic, as opposed to gametic), then an organism develops with cells of different chromosomal constitutions (two types or more). Such forms of chromosomal diseases are called mosaic. For the appearance of mosaic forms, the clinical picture of which coincides with the full forms, at least 10% of cells with an abnormal set are needed.

The third principle is identifying the generation in which it arose la mutation : it arose anew in the gametes of healthy parents (sporadic cases) or the parents already had such an anomaly (inherited, or familial, forms). No more than 3-5 are passed on from generation to generation % of them. Chromosomal disorders are responsible for approximately 50% of spontaneous abortions and 7% of all stillbirths.

All chromosomal diseases are usually divided into two groups.

Diseases associated with abnormalitiesnumber of chromosomes

This group includes three subgroups:

Diseases caused by number disorders

Diseases associated with an increase or decrease in the number of sex X and Y chromosomes.

3. Diseases caused by polyploidy

A multiple increase in the haploid set of chromosomes.

Diseases associated with structuralviolations

(aberrations)chromosomes

Their reasons are:

Translocations are exchange rearrangements between non-homologous chromosomes.

Deletions are the loss of a section of a chromosome.

Inversions are rotations of a chromosome section by 180 degrees.

Duplications - doubling of a chromosome section

Isochromosomy - chromosomes with repeated genetic material in both arms.

The appearance of ring chromosomes (connection of two terminal deletions in both arms of a chromosome).

Currently, more than 700 diseases caused by structural abnormalities of chromosomes are known in humans. Available data show that about 25% are due to autosomal trisomies, 46% are due to pathology of sex chromosomes. Structural adjustments account for 10.4%. Among chromosomal rearrangements, translocations and deletions are the most common.

Diseases associated with chromosome aberrations

Down syndrome (trisomy 21 chromosome). The most common disease with a quantitative chromosome disorder is trisomy 21 (the presence of 47 chromosomes instead of 46 due to an extra chromosome of the 21st pair). Trisomy 21, or Down Syndrome, occurs with a frequency of 1 in 700-800 births, does not have any temporal, ethnic or geographical difference when the parents are the same age. This disease is one of the most common and studied human pathologies. The frequency of births of children with Down syndrome depends on the age of the mother and, to a lesser extent, on the age of the father.

With age, the likelihood of having children with Down syndrome increases significantly. So, in women aged 45 years it is about 3%. A high incidence of children with Down syndrome (about 2%) is observed in women who give birth early (before 18 years of age). Therefore, for population comparisons of the frequency of births of children with Down syndrome, it is necessary to take into account the distribution of women giving birth by age (the proportion of women giving birth after 30-35 years, in the total number of women giving birth). This distribution sometimes changes within 2-3 years for the same population (for example, with a sharp change in the economic situation in the country). The increase in the incidence of Down syndrome with increasing maternal age is known, but the majority of children with Down syndrome are still born to mothers under 30 years of age. This is due to the higher number of pregnancies in this age group compared to older women.

The literature describes the “bundling” of births of children with Down syndrome at certain periods of time in some countries (cities, provinces). These cases can be explained more by stochastic fluctuations in the spontaneous level of chromosome nondisjunction than by the influence of putative etiological factors (viral infection, low doses of radiation, chlorophos).

Clinically, Down syndrome was described in 1866. Its genetic nature was deciphered much later - in 1959, when Lejeune and his colleagues discovered an extra chromosome 21 in the karyotype of these patients. Rarer cytogenetic variants of Down syndrome - translocation and mosaic - have also been described. The translocation variant accounts for about 3% of cases. The number of chromosomes in the karyotype of such patients is normal - 46, since the additional 21st chromosome is translocated (moved) to another autosome. Mosaic variants account for 2% of all cases of the disease.

The ratio of boys to girls with Down syndrome is 1:1.

The clinical symptoms of Down syndrome are varied: these include congenital malformations, disorders of postnatal development of the nervous system, secondary immunodeficiency, etc. Children with Down syndrome are born at term, but with moderate prenatal hypoplasia (8-10% below average). Many symptoms of Down syndrome are noticeable at birth and become more pronounced later on. A qualified pediatrician installs correct diagnosis Down syndrome in the maternity hospital in at least 90% of cases. Craniofacial dysmorphias include Mongoloid eye shape (for this reason Down syndrome has long been called Mongoloidism), brachycephaly, round flattened face, flat dorsum of the nose, epicanthus, large (usually protruding) tongue, and deformed ears. Muscular hypotonia is combined with joint laxity. Often there are congenital heart defects, typical changes in dermatoglyphics (four-finger, or “monkey”, fold in the palm, two skin folds instead of three on the little finger). Gastrointestinal defects are rare.

The diagnosis of Down syndrome is made based on a combination of several symptoms. The presence of 4-5 of them reliably indicates Down syndrome: 1) flattening of the facial profile (90%); 2) absence of sucking reflex (85%); 3) muscle hypotonia (80%); 4) Mongoloid section of the palpebral fissures (80%); 5) excess skin on the neck (80%); 6) joint laxity (80%); 7) dysplastic pelvis (70%); 8) dysplastic (deformed) ears (60%); 9) clinodactyly of the little finger (60%); 10) four-finger flexion fold (transverse line) of the palm (45%). The height of adult patients is 20 cm below average.

The reaction of children with Down syndrome to environmental influences is often pathological due to weak cellular and humoral immunity, decreased DNA repair, insufficient production of digestive enzymes, and limited compensatory capabilities of all systems. For this reason, children with Down syndrome often suffer from pneumonia and have severe childhood infections. They are underweight and have severe hypovitaminosis.

Congenital defects of internal organs and reduced adaptability of children with Down syndrome often lead to death in the first 5 years. The consequence of altered immunity and insufficiency of repair systems (for damaged DNA) are leukemias, which often occur in patients with Down syndrome.

The mental development of patients with Down syndrome lags behind. Mental retardation can reach the level of imbecility without special teaching methods. The mental development quotient (IQ) of different children can range from 25 to 75. Children with Down syndrome are affectionate, attentive, obedient, and patient when learning.

Diagnosis of this syndrome does not cause any particular difficulties. An important problem at present is a radical change in public opinion and the opinion of specialists regarding the learning ability of these children, the need for developmental education and integration into the environment of healthy peers, the importance of developing and implementing special programs for their social adaptation and creative development.

90% of children with Down syndrome born in Russia are left by their parents in the care of the state. Parents often do not know that with proper training, such children can become full-fledged members of society.

Therapeutic care for children with Down syndrome is multifaceted and nonspecific. Congenital heart defects are eliminated promptly. General strengthening treatment is constantly carried out. Nutrition should be complete. Attentive care for a sick child and protection from harmful environmental factors (colds, infections) are necessary. Great successes in preserving the lives of children with Down syndrome and their development are provided by special teaching methods, strengthening physical health from early childhood, and some forms of drug therapy aimed at improving the functions of the central nervous system. Many patients with trisomy 21 are now able to lead an independent life, master simple professions, and start families.

Patau syndrome (trisomy 13 chromosome) described in 1960 in children with multiple congenital malformations. Occurs in newborns with a frequency of 1:5000 - 1:7000. The disease is caused by trisomy on chromosome 13 in 80-85% of patients with Patau syndrome. Chromosome nondisjunction in meiosis occurs most often in the mother. Boys and girls with Patau syndrome are born at the same rate.

A characteristic complication of pregnancy when carrying a fetus with Patau syndrome is polyhydramnios: it occurs in almost 50% of cases. Patau syndrome is accompanied by multiple congenital malformations of the brain and face. This is a pathogenetically unified group of early (and, therefore, severe) disorders of the formation of the brain, eyeballs, bones of the brain and facial parts of the skull. Skull circumference is usually reduced. The forehead is sloping, low; the palpebral fissures are narrow, the bridge of the nose is sunken, the ears are low and deformed. A typical sign of Patau syndrome is cleft lip and palate (usually bilateral). Defects of several internal organs are always found in different combinations: heart septal defects, incomplete intestinal rotation, kidney cysts, anomalies of the internal genital organs (in girls this is a duplication of the uterus and vagina, in boys - cryptorchidism - retention of the testicle when descending into the scrotum), pancreatic defects glands. As a rule, polydactyly is observed (usually bilateral and on the hands). Deafness is detected in 80-85% of patients. At birth, sick children are characterized by low weight, although they are born at term.

Due to severe congenital malformations, most children with Patau syndrome die in the first weeks or months of life (95% die before 1 year of age). However, some patients live for several years. Moreover, in developed countries there is a tendency to increase the life expectancy of patients with Patau syndrome to 5 years (about 15% of patients) and even up to 10 years (2-3% of patients).

Therapeutic care for children with Patau syndrome is nonspecific: operations for congenital malformations (for health reasons), restorative treatment, careful care, prevention of colds and infectious diseases. Children with Patau syndrome are almost always profound idiots.

Edwards syndrome (trisomy) 18th chromosome). Described in 1960 Edwards. The frequency of patients among newborns is 1:5000 - 1:7000. The ratio of boys to girls with Edwards syndrome is 1:3. The reasons for the predominance of sick girls are not yet known. In almost all cases, Edwards syndrome is caused by a simple trisomic form (a gametic mutation in one of the parents).

With Edwards syndrome, there is a pronounced delay in prenatal development with a normal duration of pregnancy (delivery at term). The most characteristic features of the syndrome are multiple birth defects development of the facial part of the skull, heart, skeletal system, genital organs. The skull is dolichocephalic (elongated) in shape; the lower jaw and mouth opening are small; palpebral fissures are narrow and short; the ears are deformed and low-set. Other external signs include a flexor position of the hands, an abnormal foot (the heel protrudes, the arch sags), the first toe is shorter than the second toe. Spina bifida and cleft lip are rare (5% of Edwards syndrome cases).

Children with Edwards syndrome die at an early age (90% before 1 year) from complications caused by congenital malformations (asphyxia, pneumonia, intestinal obstruction, cardiovascular failure).

Syndromes caused byintrachromosomal

perestroikas

This type of chromosome rearrangements (along with deletions, duplications and inversions) includes partial trisomies and autosomal monosomies.

Cry of the cat syndrome associated with a deletion of the short arm of chromosome 5. It was first described by J. Lejeune in 1963. Its sign is the unusual crying of children, reminiscent of the meowing or cry of a cat. This is due to pathology of the larynx or vocal cords. However, with age, this cry disappears.

The clinical picture of the syndrome varies significantly. The most typical, in addition to the “cry of a cat,” is mental and physical underdevelopment, microcephaly (an abnormally small head).

The appearance of patients is peculiar: moon-shaped face, microgenia (small size of the upper jaw), epicanthus (vertical fold of skin at the inner corner of the palpebral fissure), high palate, flat dorsum of the nose, strabismus. The ears are low and deformed. Congenital heart defects, pathology of the musculoskeletal system, syndactyly of the feet (complete or partial fusion of adjacent toes), flat feet, clubfoot, etc., and muscle hypotonia are also noted.

Most children die at an early age. However, descriptions of patients over 50 years of age are known. The population frequency of “cry the cat” syndrome is 1:40000 - 1:50000 newborns. The size of the deletion varies from case to case.

Wolf-Hirschhorn syndrome first described in 1965. In 80% of newborns suffering from it, the cytological basis of this syndrome is a deletion of the short arm of chromosome 4. It is noted that most deletions arise anew, about 13% occur as a result of translocations in the parents. Less commonly, in the genome of patients, in addition to translocation, there are also ring chromosomes. Along with chromosome divisions, pathology in newborns can be caused by inversions, duplications, and isochromosomes.

The disease is characterized by numerous congenital malformations and delayed mental and psychomotor development.

Newborns have a low weight during a normal pregnancy. Among the external signs are: microcephaly, beak-shaped nose, epicanthus, anti-Mongoloid eye shape (drooping of the outer corners of the palpebral fissures), abnormal ears, cleft lip and palate, small mouth, deformed feet, etc.

The frequency of this syndrome is low - 1:100,000 births.

The vitality of children is sharply reduced, most die before the age of 1 year. Only 1 patient aged 25 years is described.

Syndromes with numbersabnormalities of sex chromosomes

Shereshevsky-Turner syndrome first described by N.A. Shereshevsky in 1925, and later, in 1938, Kh.Kh. Turner. The cause of the disease is a violation of the divergence of sex chromosomes. Only women are affected; they are missing one X chromosome (45 XO).

The incidence of the syndrome is 1:3000 newborn girls. It is noted that only 20% of women remain pregnant with a diseased fetus until the end and a live child is born. In other cases, spontaneous abortion or stillbirth occurs.

The syndrome is characterized by: short stature, sexual infantilism, somatic disorders. Children experience growth retardation already in the first year of life, which becomes most clearly noticeable by the age of 9-10 years. The average height of sick adult women is 135 cm. They have anomalies in skeletal development: a short neck with lateral skin folds, a short and wide chest, excessive mobility of the elbow and knee joints, shortening of the 4th-5th fingers. The appearance of patients is characteristic: micrognathia (underdevelopment of the lower jaw), epicanthus, low-set deformed ears, high hard palate, etc. Strabismus, cataracts, hearing defects, anomalies of the urinary system (doubling of the kidneys, urinary tract) are often noted.

An important feature of this disease is sexual infantilism. The internal and external genitalia are underdeveloped, during puberty secondary sexual characteristics are absent or poorly developed, the vagina and uterus are underdeveloped, there are no menstruation, patients are infertile. However, in the literature there is data on the birth of children in women with Shereshevsky-Turner syndrome.

In 50% of cases, patients suffer from mental retardation, they are passive, prone to psychogenic reactions and psychosis.

Life expectancy is close to normal. Treatment is aimed at stimulating growth and reducing sexual infantilism (long courses of sex hormones, etc.).

X-chromosomy polysomy syndrome meh in women. The syndrome includes trisomy (karyotype 47, XXX), tetrasomy (48, XXXX), pentasomy (49, XXXXX). Trisomy is the most common - 1 in 1000 girls born. The clinical picture is quite varied. There is a slight decrease in intelligence, an increased likelihood of developing psychosis and schizophrenia with an unfavorable type of course. The fertility of such women suffers to a lesser extent.

With tetra- and pentasomy - X, the degree of mental retardation increases, somatic anomalies and underdevelopment of the genitals are noted. Diagnosis of polysomy X syndrome includes determination of sex chromatin and examination of the patient's karyotype. There is no rational treatment.

Klinefelter syndrome described in 1942 by N. Klinefelter. Only boys get sick. The frequency of occurrence is 2 out of 1000 newborn boys. It has been established that patients have an extra X chromosome (karyotype 47, XXY, instead of 46, XY). Along with this, there are polysomy variants with a large number of X and Y chromosomes, which are also classified as Klinefelter syndrome.

The disease is not clinically diagnosed before birth. Genetic abnormalities manifest themselves during puberty in the form of underdevelopment of the testes and secondary sexual characteristics.

Men with Klinefelter syndrome are characterized by high stature, eunuchoid body type (wide pelvis, narrow shoulders), gynecomastia (more than normal development of the mammary glands), poor facial hair growth, armpits and on the pubis. The testicles are reduced in size, sexual infantilism and a tendency to obesity are noted. In this case, spermatogenesis is impaired in patients and they are infertile. Their mental development lags behind, however, sometimes the intelligence is normal.

An increase in the number of X chromosomes in the genotype is accompanied by increased mental retardation, mental disorders, antisocial behavior and alcoholism.

Disomy syndrome Y -chromosome (47, XYY) was described in 1961. It occurs with a frequency of 1 in 1000 newborn boys. Men with a set of chromosomes 47 XYY do not differ from the norm in physical and mental development. There is a slight increase in height - about 185 cm. Sometimes there is a slight decrease in intelligence, a tendency to aggressive and antisocial behavior. According to some data, in prison there are 10 times more men with the XYY genotype than men with the normal genotype.

Factors that increase the risk of having children with

chromosomal diseases

In recent decades, many researchers have turned to the causes of chromosomal diseases. There was no doubt that the formation of chromosomal abnormalities (both chromosomal and genomic mutations) occurs spontaneously. The results of experimental genetics were extrapolated and induced mutagenesis in humans was assumed (ionizing radiation, chemical mutagens, viruses). However, the actual reasons for the occurrence of chromosomal and genomic mutations in germ cells or in the early stages of embryo development have not yet been deciphered.

Many hypotheses of chromosome nondisjunction were tested (seasonality, race-ethnicity, maternal and paternal age, delayed fertilization, birth order, family accumulation, drug treatment of mothers, bad habits, non-hormonal and hormonal contraception, viral diseases in women). In most cases, these hypotheses were not confirmed, but a genetic predisposition to the disease cannot be excluded. Although most cases of chromosome nondisjunction in humans are sporadic, it can be assumed that it is genetically determined to a certain extent. This is evidenced by the following facts:

offspring with trisomy appear repeatedly in the same women with a frequency of at least 1%;

relatives of a proband with trisomy 21 or other aneuploidies have a slightly increased risk of having a child with aneuploidy;

consanguinity of parents may increase the risk of trisomy in offspring;

the frequency of conceptions with double aneuploidy may be higher than predicted, consistent with the frequency of individual aneuploidies.

Biological factors that increase the risk of chromosome nondisjunction include maternal age, although the mechanisms of this phenomenon are unclear. The risk of having a child with a chromosomal disease caused by aneuploidy gradually increases with maternal age, but especially sharply after 35 years. In women over 45 years of age, every 5th pregnancy ends in the birth of a child with a chromosomal disease. The age dependence is most clearly manifested for trisomy 21 (Down's disease). For sex chromosome aneuploidies, the age of the parents either does not matter at all or its role is very insignificant.

With age, the frequency of spontaneous abortions also increases, which by 45 years increases by 3 times or more. This situation can be explained by the fact that spontaneous abortions are largely caused (up to 40-45%) by chromosomal abnormalities, the frequency of which is age dependent.

Diseases with hereditary predisposition

(multifactorial)

Diseases with a hereditary predisposition, in contrast to genetic diseases, are caused by both hereditary and, to a large extent, environmental factors. This group of diseases currently accounts for 92% of the total number of hereditary human pathologies. With age, the incidence of diseases increases. In childhood, the percentage of patients is at least 10%, and in the elderly - 25-30%.

The most common multifactorial diseases include: rheumatism, coronary heart disease, hypertension and peptic ulcers, liver cirrhosis, diabetes, bronchial asthma, psoriasis, schizophrenia, etc.

Diseases with a hereditary predisposition are associated with the action of many genes, which is why they are also called multifactorial.

Being multifactorial systems, they are difficult for genetic analysis. Only recently have advances in the study of the human genome and mapping of its genes opened up the possibility of identifying genetic predisposition and the main causes of the development of multifactorial diseases.

Hereditary predisposition may be mono- or polygenic in nature. In the first case, it is caused by a mutation of one gene, the manifestation of which requires a certain external factor, and in the second case, by a combination of alleles of several genes and a complex of environmental factors.

The clinical picture and severity of multifactorial human diseases are very different depending on gender and age. At the same time, with all their diversity, the following common features are distinguished:

1. High frequency of diseases in the population. Thus, about 1% of the population suffers from schizophrenia, 5% from diabetes mellitus, allergic diseases - more than 10%, hypertension - about 30%.

Clinical polymorphism of diseases varies from hidden subclinical forms to pronounced manifestations.

Features of inheritance of diseases do not correspond to Mendelian patterns.

The degree of manifestation of the disease depends on the gender and age of the patient, the intensity of the work of his endocrine system, unfavorable external factors and internal environment, for example, poor nutrition, etc.

Genetic prognosis for multifactorial diseases depends on the following factors:

the lower the frequency of the disease in the population, the higher the risk for the relatives of the proband;

how stronger degree severity of the disease in the proband, the more more risk development of the disease in his relatives;

the risk to relatives of the proband depends on the degree of relationship with the affected family member;

the risk for relatives will be higher if the proband belongs to the less affected sex;

To assess risk for multifactorial pathology, empirical data are collected on the population and family frequency of each disease or developmental defect.

The polygenic nature of diseases with hereditary predisposition is confirmed using genealogical, twin and population statistical methods. The twin method is quite objective and sensitive. When using it, a comparison is made of the concordance of mono- and dizygotic twins or a comparison of the concordance of monozygotic twins raised together or separately. It has been shown that the concordance of monozygotic twins is higher than that of dizygotic twins for a number of diseases of the cardiovascular system (hypertension, myocardial infarction, stroke, rheumatism). This indicates a genetic predisposition to these diseases. A study of the nature of malignant neoplasms in monozygotic twins showed low concordance (11%), but at the same time, it is 3-4 times higher than that for dizygotic twins. It is obvious that the importance of external factors (especially carcinogenic ones) for the occurrence of cancer is much greater than hereditary ones.

Using the twin method, a hereditary predisposition to some infectious diseases (tuberculosis, polio) and many common diseases (coronary heart disease, rheumatism, diabetes mellitus, peptic ulcer, schizophrenia, etc.) is shown.

The distribution of multifactorial diseases in different human populations can vary significantly, which is associated with differences in genetic and environmental factors. As a result of genetic processes occurring in human populations (selection, mutations, migrations, genetic drift), the frequency of genes that determine hereditary predisposition can increase or decrease until they are completely eliminated.

The successes of the Human Genome program, the isolation and decoding of the molecular organization of genes, and the study of the causes of their pathology will undoubtedly contribute to the development of preventive measures and the identification of groups of people prone to multifactorial diseases.

T E M A No. 8 Medical genetic counseling

Currently, the number of children with severe hereditary diseases in the countries of the former CIS exceeds one million. Enormous amounts of money are spent on their treatment. In this regard, diagnosis, prevention and treatment of hereditary and congenital diseases in children acquires great importance.

The most effective method of preventing hereditary pathology is medical genetic counseling, the main goal of which is to determine the prognosis for the birth of sick children in the family, as well as counseling on further family planning.

The first medical genetic consultation was organized in the late 20s. in Moscow, the largest domestic neurologist and geneticist S.N. Davidenkov at the Institute of Neuropsychiatric Prevention.

The first office for medical genetic counseling was organized in 1941 by J. Neal at the University of Michigan (USA). In Russia in 1932 under the leadership of S. G. Levit, a medical genetics institute was created.

Intensive development of medical genetic care in our and other countries began in the 60-70s. XX century, which was associated both with the increase in the proportion of hereditary diseases and with advances in the study of chromosomal pathology and metabolic diseases. According to 1995 data, there were 70 medical genetic institutions on the territory of the Russian Federation, whose services were used by about 80 thousand families.

Main target medical and genetic counseling - preventing the birth of a sick child. Main tasks medical genetic counseling are:

Establishing an accurate diagnosis of hereditary pathology.

Prenatal (antenatal) diagnosis of congenital and hereditary diseases using various methods (ultrasound, cytogenetic, biochemical, molecular genetic).

Determination of the type of inheritance of the disease.

Assessing the risk of having a sick child and providing assistance in decision making.

Promotion of medical and genetic knowledge among doctors and the population.

Occasion for medical genetic counseling may be:

The birth of a child with congenital malformations, mental and physical retardation, blindness and deafness, seizures, etc.

Spontaneous abortions, miscarriages, stillbirths.

Consanguineous marriages.

Unfavorable course of pregnancy.

Spouses work in a hazardous enterprise.

Incompatibility married couples according to the Rh factor of the blood.

The woman is over 35 years old, and the man is over 40 years old.

Medical genetic consultation includes 4 stages: diagnosis; forecast; conclusion; advice.

The work begins with clarifying the diagnosis of the disease. An accurate diagnosis is a prerequisite for any consultation. In some cases, the diagnosis of a hereditary pathology can be established by a doctor before referral to a consultation. This applies to well-studied and fairly common hereditary diseases, for example, Down's disease, diabetes mellitus, hemophilia, muscular dystrophy, etc. More often, the diagnosis is unclear.

In medical genetic consultations, the diagnosis is clarified through the use of modern genetic, biochemical, immunogenetic and other methods.

One of the main methods is the genealogical method, i.e. drawing up a pedigree for a married couple who applied for consultation. First of all, this applies to the spouse in whose pedigree there was a hereditary pathology. Careful collection of the pedigree provides certain information for making a diagnosis of the disease.

In more complex cases, for example, when a child is born with multiple developmental defects, the correct diagnosis can only be made using special research methods. During the diagnostic process, there is often a need to examine not only the patient, but also other family members.

After the diagnosis is established, the prognosis for the offspring is determined, i.e. the magnitude of the repeat risk of having a sick child. The basis for solving this problem is theoretical calculations using methods of genetic analysis and variation statistics or empirical risk tables. This is the function of a geneticist.

Transmission of hereditary diseases is possible in several ways, depending on the characteristics of the transmission of hereditary pathology. For example, if a child has a disease like one of the parents, this indicates a dominant type of inheritance. In this case, with complete penetrance of the gene, sick family members will pass the disease on to half of their children.

Hereditary pathology in a child of healthy parents indicates a recessive type of inheritance. The risk of having a sick child to parents with a recessive disease is 25%. According to 1976 data, 789 recessively inherited diseases and 944 dominantly inherited diseases were known in humans.

Hereditary pathology can be linked to sex (X-linked type of inheritance). Under these conditions, the risk of disease in boys and carriage in girls is 50%. About 150 such diseases are currently known.

In the case of multifactorial diseases, genetic counseling is quite accurate. These diseases are caused by the interaction of many genes with environmental factors. The number of pathological genes and their relative contribution to the disease are unknown in most cases. To calculate genetic risk, specially developed tables of empirical risk for multifactorial diseases are used.

A genetic risk of up to 5% is considered low and is not a contraindication to having a child again in the family. A risk of 6 to 20% is considered average, and in this case a comprehensive examination is recommended for further family planning. Genetic risk over 20% is generally considered to be high risk. Further childbearing in this family is not recommended.

With chromosomal diseases, the probability of re-birth of a sick child is extremely low and does not exceed 1% (in the absence of other risk factors).

For the translocation form of Down disease, when calculating risk, it is important to determine which parent carries the balanced translocation. For example, with translocation (14/21), the risk is 10% if the carrier is the mother, and 2.5% if the carrier is the father. When the 21st chromosome is translocated to its homologue, the risk of having a sick child is 100%, regardless of which parent is the carrier of the translocation.

To determine the risk of re-birth of a child with pathology, it is important to identify heterozygous carriers of the mutant gene. Special meaning this occurs with an autosomal recessive type of inheritance, with sex-linked inheritance, and consanguineous marriages.

In some cases, heterozygous carriage is established by analyzing the pedigree, as well as by clinical and biochemical tests. So, if a father has a recessive disease linked to the X chromosome (for example, hemophilia), then with a 100% probability his daughter will be heterozygous for this gene. Along with this, a decrease in antihemophilic globulin in the blood serum in the daughters of a hemophilic father can serve as quite convincing evidence of heterozygous carriage of the hemophilia gene.

Currently, some hereditary diseases are diagnosed using DNA diagnostics.

Heterozygous carriers of defective genes should avoid consanguineous marriages, which significantly increase the risk of having children with hereditary pathology.

The conclusion of medical genetic counseling and advice to parents (the last two stages) can be combined. As a result of genetic research, a geneticist gives an opinion about the existing disease, introduces the likelihood of the disease occurring in the future, and gives appropriate recommendations. This takes into account not only the risk of having a sick child, but also the severity of the hereditary or congenital disease, the possibility of prenatal diagnosis and the effectiveness of treatment. At the same time, all decisions on further family planning are made only by the spouses.

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MOSCOW STATE TECHNICAL UNIVERSITY

named after N.E. BAUMAN

Faculty of Biomedical Engineering

Department of Medical and Technical Information Technologies

Independent work

Diseases associated with disorders of amino acid metabolism and their biochemical essence

Student: Pirozhkova A.A. Group:BMT2-32

Head: Ershov Yu.A.

Moscow 2014

Amino acid concept

Amino acid metabolism

Diseases associated with impaired amino acid metabolism

Conclusion

Bibliography

Amino acid concept

amino acid metabolism deamination

Amino acids are the most important, and some of them vital, organic compounds, the molecule of which simultaneously contains carboxyl and amine groups.

Amino acids perform many functions in living organisms. They are structural elements of peptides and proteins, as well as other natural compounds. To build all proteins, whether proteins from the most ancient lineages of bacteria or from higher organisms, the same set of 20 different amino acids is used, covalently linked to each other in a specific sequence characteristic only of a given protein. A truly remarkable property of cells is their ability to combine 20 amino acids in various combinations and sequences, resulting in the formation of peptides and proteins with completely different properties and biological activities. From the same building blocks different organisms capable of producing such diverse products as enzymes, hormones, lens protein, feathers, cobwebs, milk proteins, antibiotics, toxic substances of fungi and many other compounds endowed with specific activity. Also, some of the amino acids are neurotransmitters or precursors of neurotransmitters, neurotransmitters or hormones.

Amino acid metabolism

The most important and irreplaceable role in the life of organisms is played by amino acid metabolism. Non-proteinogenic amino acids are formed as intermediate products during the biosynthesis and degradation of proteinogenic amino acids or in the urea cycle. In addition, for animals and humans, amino acids - the building blocks of protein molecules - are the main sources of organic nitrogen, which is used primarily for the synthesis specific to the body proteins and peptides, and of them - nitrogen-containing substances of non-protein nature (purine and pyrimidine bases, porphyrins, hormones, etc.).

When needed, amino acids can serve as a source of energy for the body, mainly through the oxidation of their carbon skeleton.

The main directions of amino acid metabolism

The apparent constancy of the chemical composition of a living organism is maintained due to the balance between the processes of synthesis and destruction of its constituent components, i.e. balance between catabolism and anabolism. In a growing organism, this balance is shifted towards protein synthesis, i.e. the anabolic function prevails over the catabolic one. In the body of an adult, up to 400 g of protein is renewed daily as a result of biosynthesis. Moreover, different proteins updated from at different speeds- from a few minutes to 10 or more days, and a protein such as collagen is practically not renewed during the entire life of the body. In general, the half-life of all proteins in the human body is about 80 days. Of these, approximately a quarter of the proteinogenic amino acids (about 100 g) decomposes irreversibly, which must be renewed by food proteins; the remaining amino acids are partially synthesized by the body.

If there is insufficient protein intake from food, the body uses proteins from some tissues (liver, muscles, plasma, etc.) for the targeted synthesis of proteins from other vital organs and tissues: heart muscle, etc. Biosynthesis of proteins is carried out only if all 20 natural amino acids are present as initial monomers, each in the right amount. Long-term absence and insufficient supply of even one of the 20 amino acids leads to irreversible changes in organism.

Proteins and amino acids are the most important nitrogen-containing compounds of animal organisms - they account for more than 95% of biogenic nitrogen. The concept of nitrogen balance (NA) is inextricably linked with the metabolism of proteins and amino acids, which is understood as the difference between the amount of nitrogen introduced into the body with food (Nin) and the amount of nitrogen removed from the body (Nex) in the form of end products of nitrogen metabolism, mainly urea:

AB = N input - N output, [g day -1 ]

With a positive nitrogen balance, the biosynthesis of proteins prevails over the processes of their breakdown, i.e. Less nitrogen is excreted from the body than it enters. A positive nitrogen balance is observed during the period of growth of the body, as well as during recovery from debilitating diseases. With a negative nitrogen balance, the breakdown of proteins prevails over their synthesis, and more nitrogen is excreted from the body than it enters. This condition is possible with aging of the body, starvation and various debilitating diseases. Normally, a practically healthy adult has nitrogen balance, i.e. the amount of nitrogen introduced into the body is equal to the amount excreted. Protein norms in the diet when nitrogen balance is achieved average 100-120 g day -1.

Absorption of free amino acids formed as a result of protein hydrolysis occurs mainly in the small intestine. This process is an active transport of amino acid molecules, requiring energy and depending on the concentration of Na+ ions. More than five specific transport systems, each of which transports amino acids that are closest in chemical structure. Different amino acids can compete with each other for binding sites on membrane-embedded transport proteins (see Chapter 15 of this Section). Thus, the absorbed amino acids in the intestine enter the liver through the portal system and then enter the blood.

Further catabolism of amino acids to final products is a combination of deamination, transamination and decarboxylation reactions. Moreover, each individual amino acid has its own specific metabolic pathway.

Deamination/Transdeamination/Decarboxylation

Deamination is the removal of amino groups from amino acids to form ammonia. It is with deamination reactions that the catabolism of amino acids most often begins. In living organisms, four types of amino acid deamination are possible.

The common product of all four types of deamination is ammonia, a compound that is quite toxic to cells and tissues, so it is neutralized in the body (see below). As a result of deamination, due to amino groups “lost” in the form of ammonia, the total amount of amino acids decreases. Most living organisms, including humans, are characterized by oxidative deamination of amino acids, while other types of deamination are found only in some microorganisms.

Oxidative deamination of L-amino acids is carried out by oxidases present in the liver and kidneys. A common coenzyme of L-amino acid oxidase is FMN, which acts as a hydrogen transporter from amino acid to oxygen. The overall oxidative deamination reaction is as follows:

R-CH(NH 2)-COOH + FMN + H 2 O >

> R-CO-COOH + FMNN 2 + NH 3 + H 2 O 2

The reaction produces an intermediate, an imino acid, which then hydrates to form a keto acid. In addition to keto acid and ammonia - as the main deamination products, this reaction also produces hydrogen peroxide, which then decomposes into water and oxygen with the participation of catalase:

H 2 O 2 > H 2 O + SO 2

Oxidative deamination, as an independent process, plays a minor role in the conversion of amino groups of amino acids; deaminates at high speed only glutamic acid. This reaction is catalyzed by the enzyme glutamate dehydrogenase, the coenzyme of which is NAD or NADH. The activity of glutamate dehydrogenase is regulated by allosteric modifiers, GTP and ATP act as inhibitors, and GDP and ADP act as activators. Oxidative deamination of glutamic acid can be represented by the following scheme:

NOOS-CH 2 -CH 2 -CH(NH 2)-COOH + NAD >

> HOOC-CH 2 -CH 2 -CO-COOH + NH3 + (NADH + H+)

This reaction is reversible, but under living cell conditions the equilibrium of the reaction is shifted towards the formation of ammonia. Other, non-oxidative types of deamination are characteristic of serine, cysteine, threonine and histidine. The remaining amino acids undergo transdeamination.

Transdeamination is the main pathway for the catabolic breakdown of amino acids. From the name of the process it is easy to guess that it occurs in two stages. The first is transamination, and the second is the actual oxidative deamination of the amino acid. Transamination is catalyzed by aminotransferase enzymes, also called simply transaminases. Pyridoxal phosphate (vitamin B6) acts as a coenzyme aminotransferase. The essence of transamination is the transfer of an amino group from a b-amino acid to a b-keto acid. Thus, the transamination reaction is an intermolecular redox process in which the carbon atoms of not only interacting amino acids, but also pyridoxal phosphate are involved.

Decarboxylation is the process of removing a carboxyl group from an amino acid in the form of CO2. Some amino acids and their derivatives can undergo decarboxylation under living organism conditions. Decarboxylation is catalyzed by special enzymes - decarboxylases, the coenzyme of which (with the exception of histidine decarboxylase) is pyridoxal phosphate. The products of decarboxylation are amines that have biological activity - biogenic amines. Most neurotransmitters and local regulatory factors (tissue mediators that regulate metabolism) belong to this group of compounds. The decarboxylation reaction of an arbitrary amino acid can be represented as follows:

DecarboxylaseBiogenic amine

Formation of biologically active amines

GABA is a neurotransmitter of the nervous system (gamma-aminobutyric acid).

Glutamate

Histamine is a mediator of inflammation and allergic reactions.

HistidineHistamine

Table Predecessors chemical structure, biological role of biogenic amines

Diseases associated with amino acid metabolism disorders

Metabolism in the body is a very important process. Any deviation from the norm can lead to a deterioration in a person’s health. There are hereditary and acquired disorders of amino acid metabolism. The highest rate of amino acid metabolism is observed in nervous tissue. For this reason, in psychoneurological practice, various hereditary aminoacidopathies are considered one of the causes of dementia.

Tyrosine metabolism disorder.

Tyrosine, in addition to its role in protein synthesis, is a precursor of the adrenal hormones adrenaline, norepinephrine, the mediator dopamine, the thyroid hormones thyroxine triiodothyronine, and pigments. There are numerous disorders of tyrosine metabolism and are called tyrosinemia.

Tyrosinemia type I.

Etiology.

The disease occurs due to deficiency of fumarylacetoacetate hydrolase. In this case, fumarylacetoacetate and its metabolites accumulate, affecting the liver and kidneys.

Fumarylaceto hydrolase

Clinical picture.

The acute form accounts for the majority of cases with onset between 2 and 7 months of age. and death of 90% of patients aged 1-2 years due to liver failure.

In the chronic form, the disease develops later and progresses more slowly. Life expectancy is about 10 years.

Basics of treatment.

Treatment is ineffective. A diet with a decrease in the amount of protein, phenylalanine and tyrosine, and glutathione injections are used. A liver transplant is required.

Tyrosinemia type 2.

A much rarer disease.

Etiology.

The disease occurs due to deficiency of tyrosine aminotransferase.

Clinical picture.

Delayed mental and physical development, microcephaly, cataracts and corneal keratosis (pseudoherpetic keratitis), skin hyperkeratosis, self-mutilation, impaired fine coordination of movements.

A diet low in tyrosine is effective, and skin and corneal lesions quickly disappear.

Tyrosinemia of newborns.

Etiology.

Neonatal tyrosinemia (type 3) is the result of hydroxyphenylpyruvate hydroxylase deficiency. More often observed in premature babies.

Clinical picture.

Reduced activity and lethargy. The anomaly is considered harmless. Ascorbic acid deficiency enhances the clinical picture.

Basics of treatment.

A diet with reduced amounts of protein, phenylalanine, tyrosine and high doses of ascorbic acid.

Alkaptonuria.

Etiology.

Genetic autosomal recessive enzymopathy. The disease is based on a decrease in the activity of the liver enzyme homogentisate oxidase, as a result of which homogentisic acid accumulates in the body.

Clinical picture.

Since the homogentisate polymerizes in air into a melanin-like compound, the most common and constant symptom is dark urine, dark brown stains remain on the diaper and underwear. The disease does not manifest itself in any other way in childhood.

With age, homogentisin acid accumulates in connective tissue formations, sclera and skin, causing a slate-deep shade of the ear and nasal cartilage, staining areas of clothing, sweating areas of the body (armpits).

At the same time, homogentisinic acid inhibits lysyl hydroxylase, preventing collagen synthesis, which makes cartilage formations fragile. By old age, degenerative arthrosis of the spine and large joints occurs, the intervertebral spaces are narrowed.

Basics of treatment.

Although effective ways unknown, by analogy with other amino acid disorders, it is recommended to limit the intake of phenylalanine and tyrosine from an early age, which should prevent the development of ochronosis and joint disorders. Large doses of ascorbic acid are prescribed to protect the activity of lysyl oxidase.

Albinism.

Etiology. The disease is caused by a complete or partial defect in the synthesis of the enzyme tyrosinase (frequency 1:20000), necessary for the synthesis of dioxyphenylalanine in pigment cells.

Clinical picture. In the complete absence of the enzyme, there is total deligmentation of the skin, hair, eyes, and the color is the same for all racial groups and does not change with age. The skin does not tan, there are no nevi or pigment spots at all, and photodermatitis develops. Severe nystagmus, photophobia, day blindness, red pupillary reflex. With partial deficiency, light yellow hair, weakly pigmented moles, and very fair skin are noted.

Parkinsonism.

Etiology. The cause of parkinsonism (frequency after 60 years 1:200) is low activity tyrosine hydroxylase or DOPA decaboxylase in the nervous tissue, resulting in a deficiency of the neurotransmitter dopamine and accumulation of tyramine.

Clinical picture.

The most common symptoms are muscle stiffness, stiffness, tremors and spontaneous movements.

Basics of treatment.

Requires systematic introduction medicinal analogues dopamine and the use of monoamine oxidase inhibitors.

Fumarate Acetoacetate

Fumarate acetoacetate

Phenylketonuria

Etiology. Phenylalanine hydroxylase deficiency. Phenylalanine is converted to phenylpyruvate.

Clinical picture.

§ Disturbance of nerve myelination

§ Brain mass is below normal.

§ Mental and physical retardation.

Diagnostic criteria:

§ level of phenylalanine in the blood.

§ FeCl3 test.

§ DNA samples (prenatal).

Conclusion

The importance of amino acids for the body is primarily determined by the fact that they are used for the synthesis of proteins, the metabolism of which occupies a special place in the metabolic processes between the body and external environment. Important role Protein hormones play a role in coordinating the work of all cell systems. The metabolism of proteins and amino acids plays a vital and irreplaceable role in the life of organisms.

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12. http://biomed.science.ulster.ac.uk/bmsri/-Metabolomics-and-Proteomics-Unit-.html

13. http://biokhimija.ru/lekcii-po-biohimii/21-matrichnye-biosintezy.html

14. Biochemistry: Textbook. for universities, Ed. E.S. Severina., 2003. 779 p. ISBN 5-9231-0254-4

15. Veltishchev Yu. E., Kazantseva L. Z., Semyachkina A. N. Hereditary metabolic diseases. In the book Human Hereditary Pathology, ed. Veltishchev Yu. E., Bochkov N. P. M. 1992, vol. 1, p. 41-101.

16. Musil Ya., Novikova O., Kunz K. Modern biochemistry in schemes: Transl. from English - 2nd ed., corrected - M.: Mir, 1984. - 216 pp., ill.

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The largest group of hereditary metabolic diseases. Almost all of them are inherited in an autosomal recessive manner. The cause of diseases is the deficiency of one or another enzyme responsible for the synthesis of amino acids. These include:

• phenylketonuria - a disorder in the conversion of phenylalanine to tyrosine due to sharp decline phenylalanine hydroxylase activity;
• alkaptonuria - a disorder of tyrosine metabolism due to decreased activity the enzyme homogentisinase and the accumulation of homotentisic acid in the tissues of the body;
• oculocutaneous albinism is caused by the lack of synthesis of the enzyme tyrosinase.

PHENYLKETONURIA (PKU) is a severe hereditary disease that is characterized mainly by damage to the nervous system. As a result of a mutation in the gene that controls the synthesis of phenylalanine hydroxylase, a metabolic block develops at the stage of conversion of phenylalanine to tyrosine, as a result of which the main pathway for the conversion of phenylalanine becomes deamination and the synthesis of toxic derivatives - phenylpyruvic, phenyllactic and phenylacetic acids. In the blood and tissues, the fnylalanine content increases significantly (up to 0.2 g/l or more, with a norm of 0.01-0.02 g/l). Insufficient synthesis of tyrosine, which is a precursor of catecholamines and melanin, plays a significant role in the pathogenesis of the disease. The disease is inherited in an autosomal recessive manner.

DISORDERS OF AMINO ACID METABOLISM. The most common diseases associated with impaired amino acid metabolism are phenylketonuria and albinism.
Normally, the amino acid phenylalanine (PA) is converted by the enzyme phenylalanine hydroxylase into the amino acid tyrosine, which in turn, under the action of the enzyme tyrosinase, can be converted into the pigment melanin. When the activity of these enzymes is disrupted, hereditary human diseases phenylketonuria and albinism develop.
Phenylketonuria (PKU) occurs in various human populations with a frequency of 1:6000-1:10,000, in Belarus - 1:6000. It is inherited in an autosomal recessive manner; patients are recessive homozygotes (aa). The mutant gene, which is responsible for the synthesis of the enzyme phenylalanine hydroxylase, has been mapped (12q22-q24), identified and sequenced (nucleotide sequence determined).
Phenylalanine is one of the essential amino acids. Only a portion of FA is used for protein synthesis; the bulk of this amino acid is oxidized to tyrosine. If the enzyme phenylalanine hydroxylase is not active, then FA is not converted into tyrosine, but accumulates in the blood serum in large quantities in the form of phenylpyruvic acid (PPVA), which is excreted in the urine and sweat, resulting in a “mouse” odor from patients. A high concentration of FPVC leads to disruption of the formation of the myelin sheath around axons in the central nervous system. Children with phenylketonuria are born healthy, but in the first weeks of life they develop clinical manifestations of the disease. FPVK is a neurotropic poison, as a result of which excitability and muscle tone increase, hyperreflexia, tremor, and convulsive epileptiform seizures develop. Later violations of higher nervous activity, mental retardation, microcephaly. Patients experience weak pigmentation due to impaired melanin synthesis.
There are three forms of this disease. Phenylketonuria I has an autosomal recessive mode of inheritance and is caused by mutations of the RAS gene, localized on the long arm of chromosome 12 (12q24.1).
Phenylketonuria //is also inherited in an autosomal recessive manner, the gene defect is localized in the short arm of chromosome 4, region 4p15.3. The incidence of the disease is 1:100,000. Due to deficiency of dihydropteridine reductase, recovery is impaired active form tetra-hydrobiopterin, participating as a cofactor in the hydroxylation of phenylalanine, tyrosine and tryptophan, which leads to the accumulation of metabolites and disruption of the formation of precursors of catecholamine and serotonin neurotransmitters. In the pathogenesis of the disease, a decrease in the level of folate in blood serum, red blood cells, and cerebrospinal fluid is also important.
Phenylketonuria III is inherited in an autosomal recessive manner and is associated with deficiency of 6-pyruvoyl-tetrahydropterin synthase, which is involved in the synthesis of tetra-hydrobiopterin from dihydroneopterin triphosphate. The frequency of the disease is 1:30,000. Tetrahydrobiopterin deficiency plays a major role in the genesis of the disease.
Diagnosis of the disease is carried out using biochemical methods: even before the development of the clinical picture, PPVC is determined in the urine, and a high content of phenylalanine is detected in the blood. In maternity hospitals, a screening test for phenylketonuria is mandatory.
Albinism occurs in different populations with different frequencies - from 1:5000 to 1:25,000. Its most common form - oculocutaneous tyrosine-negative albinism - is inherited in an autosomal recessive manner.
The main clinical manifestations of albinism at any age are the absence of melanin in skin cells (milky white color), very blond hair, light gray or light blue iris of the eyes, red pupil, increased sensitivity to UV irradiation (causes inflammatory skin diseases ). Patients do not have any pigment spots on their skin and their visual acuity is reduced. Diagnosis of the disease is not difficult.

61. Hereditary diseases carbohydrate metabolism(galactosemia)

Hereditary diseases associated with carbohydrate metabolism disorders include, for example, galactosemia, in which the process of enzymatic conversion of galactose into glucose is disrupted. As a result, galactose and its metabolic products accumulate in cells and have a damaging effect on the liver, central nervous system, etc. Clinically, galactosemia is manifested by diarrhea, vomiting from the first days of a child’s life, persistent jaundice due to damage and enlargement of the liver, clouding of the lens (cataract ), delayed mental and physical development.

Hereditary disorders of carbohydrate metabolism include diabetes(see Diabetes) and a number of other diseases.

Pathology of carbohydrate metabolism. An increase in blood glucose levels - hyperglycemia can occur due to excessively intense gluconeogenesis or as a result of a decrease in the ability to utilize glucose by tissues, for example, when the processes of its transport through the tissues are disrupted. cell membranes. A decrease in blood glucose levels - hypoglycemia - can be a symptom of various diseases and pathological conditions, and the brain is especially vulnerable in this regard: the consequences of hypoglycemia can be irreversible damage its functions.

Genetically determined defects in enzymes of U. o. are the cause of many hereditary diseases. An example of a genetically determined hereditary disorder of monosaccharide metabolism is galactosemia, developing as a result of a defect in the synthesis of the enzyme galactose-1-phosphate uridyl transferase. Signs of galactosemia are also noted with a genetic defect of UDP-glucose-4-epimerase. Characteristic features galactosemia are hypoglycemia, galactosuria, the appearance and accumulation of galactose-1-phosphate in the blood along with galactose, as well as weight loss, fatty degeneration and cirrhosis of the liver, jaundice, cataracts that develop at an early age, delayed psychomotor development. In severe forms of galactosemia, children often die in the first year of life due to impaired liver function or reduced resistance to infections.

An example of hereditary monosaccharide intolerance is fructose intolerance, which is caused by a genetic defect in fructose phosphate aldolase and, in some cases, by a decrease in the activity of fructose 1,6-diphosphate aldolase. The disease is characterized by damage to the liver and kidneys. The clinical picture is characterized by convulsions, frequent vomiting, sometimes coma. Symptoms of the disease appear in the first months of life when children are transferred to mixed or artificial nutrition. Fructose loading causes severe hypoglycemia.

Diseases caused by defects in the metabolism of oligosaccharides mainly involve impaired breakdown and absorption of dietary carbohydrates, which occurs mainly in the small intestine. Maltose and low molecular weight dextrins formed from starch and food glycogen under the action of a-amylase in saliva and pancreatic juice, milk lactose and sucrose are broken down by disaccharidases (maltase, lactase and sucrase) to the corresponding monosaccharides mainly in the microvilli of the mucous membrane of the small intestine, and then, If the transport process of monosaccharides is not disrupted, their absorption occurs. The absence or decrease in the activity of disaccharidases to the mucous membrane of the small intestine serves main reason intolerance to the corresponding disaccharides, which often leads to liver and kidney damage and causes diarrhea and flatulence (see. Malabsorption syndrome ). Particularly severe symptoms are characterized by hereditary lactose intolerance, which is usually detected from the very birth of the child. To diagnose sugar intolerance, stress tests are usually used with the administration on an empty stomach per os of a carbohydrate intolerance of which is suspected. A more accurate diagnosis can be made by biopsy of the intestinal mucosa and determination of disaccharidase activity in the resulting material. Treatment consists of eliminating foods containing the corresponding disaccharide from food. A greater effect is observed, however, when enzyme preparations are prescribed, which allows such patients to eat regular food. For example, in case of lactase deficiency, it is advisable to add an enzyme preparation containing lactase to milk before consuming it. Correct diagnosis of diseases caused by disaccharidase deficiency is extremely important. The most common diagnostic error in these cases is the establishment of a false diagnosis of dysentery, other intestinal infections, and treatment with antibiotics, leading to a rapid deterioration in the condition of sick children and serious consequences.

Diseases caused by impaired glycogen metabolism constitute a group of hereditary enzymopathies, united under the name glycogenosis. Glycogenosis is characterized by excessive accumulation of glycogen in cells, which may also be accompanied by a change in the structure of the molecules of this polysaccharide. Glycogenosis is classified as a so-called storage disease. Glycogenosis (glycogen disease) is inherited in an autosomal recessive or sex-linked manner. Almost complete absence in glycogen cells is noted in aglycogenosis, the cause of which is the complete absence or reduced activity of liver glycogen synthetase.

Diseases caused by impaired metabolism of various glycoconjugates are in most cases a consequence congenital disorders breakdown of glycolipids, glycoproteins or glycosaminoglycans (mucopolysaccharides) in various organs. They are also storage diseases. Depending on which compound abnormally accumulates in the body, glycolipidoses, glycoproteinodes, and mucopolysaccharidoses are distinguished. Many lysosomal glycosidases, the defect of which underlies hereditary disorders of carbohydrate metabolism, exist in the form of various forms, the so-called multiple forms, or isoenzymes. The disease can be caused by a defect in any one isoenzyme. For example. Tay-Sachs disease is a consequence of a defect in the AN form of acetylhexosaminidase (hexosaminidase A), while a defect in the A and B forms of this enzyme leads to Sandhoff disease.

Most storage diseases are extremely severe, many of them are still incurable. Clinical picture when various diseases accumulation may be similar, and, on the contrary, the same disease may manifest itself differently in different patients. Therefore, it is necessary in each case to establish an enzyme defect, which is detected mostly in leukocytes and fibroblasts of the skin of patients. Glycoconjugates or various synthetic glycosides are used as substrates. At different mucopolysaccharidoses, as well as in some other storage diseases (for example, with mannosidosis), oligosaccharides differing in structure are excreted in the urine in significant quantities. Isolation of these compounds from urine and their identification are carried out for the purpose of diagnosing storage diseases. Determination of enzyme activity in cultured cells isolated from amniotic fluid obtained during amniocentesis for suspected storage disease allows prenatal diagnosis.

In some diseases, serious violations of the U. o. arise secondarily. An example of such a disease is diabetes mellitus, caused either by damage to the b-cells of the pancreatic islets, or by defects in the structure of insulin itself or its receptors on the cell membranes of insulin-sensitive tissues. Nutritional hyperglycemia and hyperinsulinemia lead to the development of obesity, which increases lipolysis and the use of non-esterified fatty acids(NEFA) as an energy substrate. This impairs glucose utilization in muscle tissue and stimulates gluconeogenesis. In turn, excess NEFA and insulin in the blood leads to an increase in the synthesis of triglycerides in the liver (see. Fats ) And cholesterols and, accordingly, to an increase in blood concentration lipoproteins very low and low density. One of the reasons contributing to the development of such severe complications in diabetes, such as cataracts, nephropathy, anglopathy and tissue hypoxia, is non-enzymatic glycosylation of proteins.

62. Hereditary connective tissue diseases (mucopolysaccharidoses)

Mucopolysaccharidoses, or MPS for short, or MPS (from (mucopolysaccharides + -ōsis)) are a group of metabolic diseases of connective tissue associated with impaired metabolism of acid glycosaminoglycans (GAG, mucopolysaccharides), caused by a deficiency of lysosomal enzymes of glycosaminoglycan metabolism. The diseases are associated with hereditary metabolic abnormalities, manifest themselves as “storage diseases” and lead to various defects of bone, cartilage, and connective tissue.

Types of diseases

Depending on the nature of the enzymatic defect, several main types of mucopolysaccharidoses are distinguished:

• Type I - Hurler syndrome (mucompolysaccharidosis I H - Hurler), Hurler-Scheie syndrome (mucopolysaccharidosis I H/S - Hurler-Scheie), Scheie syndrome (mucopolysaccharidosis I S - Scheie). Caused by deficiency of alpha-L-iduronidase (enzyme of mucopolysaccharide catabolism). The disease gradually leads to the accumulation of heparan sulfate and dermatan sulfate in the tissues. There are three phenotypes: Hurler syndrome, Scheie syndrome, and Hurler-Scheie syndrome.
• Type II - Hunter syndrome
• Type III - Sanfilippo syndrome
• Type IV - Morquio syndrome
• Type V - Scheie syndrome
• Type VI - Maroteaux-Lamy syndrome
• Type VII - Sly syndrome β-glucuronidase deficiency

63. Mendelizing traits in humans

Mendelian characters are those whose inheritance occurs according to the laws established by G. Mendel. Mendelian traits are determined by one gene monogenically (from the Greek monos - one), that is, when the manifestation of a trait is determined by the interaction allelic genes, one of which dominates (suppresses) the other. Mendelian laws are valid for autosomal genes with complete penetrance (from the Latin penetrans - penetrating, reaching) and constant expressivity (degree of expression of the trait).
If the genes are localized in the sex chromosomes (with the exception of the homologous region in the X and Y chromosomes), or linked on one chromosome, or in the DNA of organelles, then the results of the crossing will not follow Mendel’s laws.
The general laws of heredity are the same for all eukaryotes. Humans also have Mendelian traits, and are characterized by all types of their inheritance: autosomal dominant, autosomal recessive, linked to sex chromosomes (with a homologous region of the X and Y chromosomes).

Types of inheritance of Mendelian traits:
I. Autosomal dominant type of inheritance. Some normal and pathological characteristics are inherited in an autosomal dominant manner:
1) white curl above the forehead;
2) hair is coarse, straight (hedgehog);
3) woolly hair - short, easily split ends, curly, fluffy;
4) the skin is thick;
5) the ability to roll the tongue into a tube;
6) Habsburg lip - the lower jaw is narrow, protruding forward, the lower lip is drooping and the mouth is half open;
7) polydactyly (from the Greek polus - numerous, daktylos - finger) - polydactyly, when there are six or more fingers;
8) syndactyly (from the Greek syn - together) - fusion of soft or bone tissues of the phalanges of two or more fingers;
9) brachydactyly (short fingers) – underdevelopment of the distal phalanges of the fingers;
10) arachnodactyly (from the Greek ahahna - spider) - highly elongated “spider” fingers

II. Autosomal recessive type of inheritance.
If recessive genes are localized in autosomes, then they can appear during the marriage of two heterozygotes or homozygotes for the recessive allele.
The following traits are inherited in an autosomal recessive manner:
1) hair is soft, straight;
2) the skin is thin;
3) blood group Rh-;
4) inability to perceive the bitter taste of phenylurea;
5) inability to fold the tongue into a tube;
6) phenylketonuria - the conversion of phenylalanine into tyrosine is blocked, which is converted into phenylpyruvic acid, which is a neurotropic poison (signs - convulsive syndromes, mental retardation, impulsivity, excitability, aggression);
7) galactosemia - accumulation of galactose in the blood, which inhibits the absorption of glucose and has toxic effect on the function of the liver, brain, lens of the eye;
8) albinism.
The frequency of recessive hereditary diseases especially increases in isolates and among populations with a high percentage of consanguineous marriages.
Some traits have long been considered Mendelian, but their mode of inheritance is likely based on a more complex genetic model and may involve more than one gene. These include:
hair color
eye color
Morton's finger
tongue curling

64. Hereditary diseases of circulating proteins (thalassemia)

Thalassemia (Cooley's anemia) is inherited in a recessive manner (bihallelic system), which is based on a decrease in the synthesis of polypeptide chains that are part of the structure of normal hemoglobin. Normally, the main variant of hemoglobin (97%) in an adult is hemoglobin A. It is a tetramer consisting of two α-chain monomers and two β-chain monomers. 3% of adult hemoglobin is represented by hemoglobin A2, consisting of two alpha and two delta chains. There are two genes HBA1 and HBA2 encoding the alpha monomer and one HBB gene encoding the beta monomer. The presence of a mutation in the hemoglobin genes can lead to disruption of the synthesis of certain types of chains.

65. Human kareotype. Structure and types of chromosomes. See question. 12 and 22

66. . Inherited circulating protein diseases (sickle cell anemia)

Sickle cell anemia is a hereditary hemoglobinopathy associated with such a violation of the structure of the hemoglobin protein, in which it acquires a special crystalline structure - the so-called hemoglobin S. Red blood cells carrying hemoglobin S instead of normal hemoglobin A, under a microscope have a characteristic crescent shape (sickle shape), for which this form of hemoglobinopathy and is called sickle cell anemia.

Red blood cells carrying hemoglobin S have reduced persistence and reduced oxygen-transporting ability, therefore, in patients with sickle cell anemia, the destruction of red blood cells in the spleen is increased, their life span is shortened, hemolysis is increased and there are often signs of chronic hypoxia ( oxygen deficiency) or chronic “over-irritation” of the erythrocyte lineage of the bone marrow.

Sickle cell anemia is inherited in an autosomal recessive manner (with incomplete dominance). In carriers who are heterozygous for the sickle cell anemia gene, their erythrocytes contain approximately equal amounts of hemoglobin S and hemoglobin A. However, under normal conditions, carriers almost never experience symptoms, and sickle erythrocytes are detected by chance during a laboratory blood test. Symptoms in carriers may appear during hypoxia (for example, when climbing mountains) or severe dehydration of the body. Homozygotes for the sickle cell anemia gene have only sickle-shaped red blood cells in their blood that carry hemoglobin S, and the disease is severe.

Sickle cell anemia is very common in regions of the world where malaria is endemic, and patients with sickle cell anemia have increased (though not absolute) innate resistance to infection by various strains of Plasmodium falciparum. The sickle-shaped red blood cells of these patients are also resistant to infection by Plasmodium falciparum in vitro. Heterozygote carriers who do not suffer from anemia also have increased resistance to malaria (heterozygote advantage), which explains the high frequency of this harmful allele in African populations.

Hyperaminoaciduria. Hyperaminoaciduria is said to occur when the excretion of one or more amino acids in the urine exceeds physiological values.
Depending on the origin, we can distinguish: 1. metabolic or prerenal and 2. renal aminoaciduria.

With metabolic aminoaciduria, one or more amino acids are formed more than normal, or less of them are metabolized. The excess exceeds the reabsorption capacity of the tubules, so amino acids “overflow” and are excreted in the urine. In these cases, along with increased aminoaciduria, an increased concentration of the corresponding amino acids in the blood is detected.

Symptomatic forms of metabolic aminoacidurias can be encountered with severe liver damage.

However, in most cases, metabolic aminoacidurias are hereditary enzymopathies: the interstitial metabolism of any amino acid is disrupted due to a lack of a certain enzyme. Metabolic products formed before the enzymatic block accumulate in the blood and are excreted in large quantities in the urine.

In renal aminoaciduria, amino acids are synthesized in normal quantity, however, due to congenital or acquired damage to the renal tubules, they are excreted in large quantities in the urine. These abnormalities are described in more detail in the chapter on kidney diseases. Only congenital metabolic aminoacidurias will be addressed here.

Phenylketonuria. Phenylpyruvic oligophrenia (Völling's disease). Enzymopathy inherited in an autosomal recessive manner. Its biochemical essence is the impossibility of converting phenylalanine into tyrosine due to the absence of the enzyme phenylalanine oxidase. The clinical manifestations of this anomaly are associated with severe brain damage accompanied by mental retardation. This common disease is one of the most common causes of mental retardation. Among the population it occurs with a frequency of 1:10,000-1:20,000.

Pathogenesis. Due to the absence of the enzyme involved in the metabolism of phenylalanine - phenylalanine oxidase, phenylalanine and the product of its metabolism - phenylpyruvic acid - accumulate in the blood. The accumulation of these substances is the cause of the leading clinical symptom - brain damage, apparently caused by the inhibitory effect of these metabolites on other enzymatic processes in the brain. In addition, disruption of the normal synthesis of tyrosine, which is the main material for the production of adrenaline, norepinephrine and diiodotyrosine, also plays a certain role in the formation of the disease.

Clinical picture. The leading symptom of phenylketonuria is mental retardation, which manifests itself in early infancy and rapidly progresses. Muscle hypertension is common, and in some cases epileptiform convulsions are observed.

Among other changes associated with metabolic defects, insufficient pigmentation of patients should be mentioned. Many of them are blue-eyed, have fair skin and blond hair. Brachycephaly and hypertaylorism are common. Arterial pressure usually low. The sweat of patients has an unpleasant (“mouse”) odor.

Diagnosis. In connection with the possibility of treating the disease, early recognition of carriers of the anomaly is of great importance. Phenylalanine and its metabolic products can be found in blood and urine. The concentration of phenylalanine in the blood is many times higher than the upper limit of normal (1.5 mg%). In urine, using the Fölling test, the presence of phenylpyruvic acid can be qualitatively demonstrated: when a solution of ferric chloride is added, the urine acquires a dark green color.

However, this test becomes positive only at the age of 3-4 weeks and, moreover, is not specific. The Guthrie test gives more accurate results already at the end of the first week: microbiological method, based on the effect that phenylalanine has on the growth of Bacillus subtilis. Of course, this method is most suitable for examining a population of infants. Its disadvantage is the need to draw blood, which is still difficult to carry out on a large scale. Until this analysis becomes universal, it is necessary to perform a ferrochloride test at 3-4 weeks of age and, in suspicious cases, confirm the diagnosis by examining the spectrum of amino acids in blood and urine using paper chromatography. In case of a family history, a blood test should be performed already in the first week of life.

Treatment . If therapy is started early, if possible as early as the neonatal period, success can be achieved by reducing the phenylalanine content in the diet to a minimum. However, the use of casein hydrolysate, which forms the basis of the diet, providing phenylalanine limitation, is difficult and expensive. Currently offered special drugs for the treatment of phenylketonuria - berlofen, lofenalac, minafen, hypophenate, which are satisfactorily tolerated by patients. With treatment started in late infancy, it is only possible to stop further progression of idiocy.

Alkaptonuria. The disease is characterized by dark brown color of urine, which appears when standing in the air. Hereditary enzymopathy, patients lack the enzyme homogentisinase. Homogentisic acid, released in larger quantities, oxidizes in air, acquiring a brown color. Diapers and underwear the child is also stained, which facilitates diagnosis.

In addition to the urine feature described above, this anomaly has only two other symptoms: arthropathy that appears at a later age and a bluish color of the cartilage, easily detected on the auricle. There is no treatment.

Albinism is also a hereditary abnormality of aromatic amino acid metabolism. At the same time, there is no enzyme tyrosinase, which catalyzes the conversion of tyrosine into DOPA - dioxyphenylalanol. Since DOPA is the basis for the synthesis of melanin, carriers of the anomaly are fair-skinned, fair-haired people, in whom a reddish vascular network is visible through the iris, which is devoid of pigmentation.

Albinism is incurable. Patients should avoid direct sunlight.

Maple syrup disease. Recessively inherited rare enzymopathy. In this disease, there is no specific decarboxylase, which is necessary for the metabolism of three important amino acids: valine, leucine and isoleucine. These amino acids and their metabolites accumulate in the blood and are excreted in significant quantities in the urine. Metabolic products give urine a special smell, reminiscent of the smell of syrup made from maple sap.

The main manifestation of the disease is brain damage, accompanied by seizures, developing in the first weeks of life and ending in death in early infancy.

When making a diagnosis, the Fölling test is important, because if it is positive, it indicates the direction of further research; An accurate diagnosis is established by examining blood and urine amino acids using paper chromatography.

For treatment Attempts are being made to improve metabolism using a synthetic diet.

Hartnup disease. A very rare hereditary disease that is accompanied by renal hyperaminoaciduria. A large amount of indican found in the urine indicates a disorder in tryptophan metabolism. Clinically characterized cerebellar ataxia and skin changes resembling pellagra.

Oxalosis. Rare hereditary disease. Due to an enzymatic block in glycocol metabolism, a large amount of oxalic acid is formed, which accumulates in the body and is excreted in the urine.

Clinically, the leading signs are pain due to kidney stones, blood and pus in the urine. In addition to the kidneys, calcium oxalate crystals are deposited in the brain, spleen, lymph nodes and bone marrow.

Diagnosis is based on the detection of hyperoxaluria and oxalate crystals in the bone marrow and lymph nodes.

In treatment- Along with symptomatic therapy, constant intake of sodium benzoate, which forms hippuric acid together with glycocol and reduces the production of oxalic acid, seems promising.

Cystinosis. Hereditary, autosomal recessive disease, which is based on the accumulation of cystine crystals in the reticuloendothelium and individual bodies and severe nephropathy developing in connection with this.

Pathogenesis disease is not clear enough, apparently we're talking about about the metabolic block in cystine catabolism.

Clinical symptoms. Among the initial changes is an increase in the size of the spleen and liver, which develops in the first months of life. Nephropathy, which decides the fate of the patient, manifests itself in the second half of life. Signs appear indicating initial tubular damage: hyperaminoaciduria, glycosuria, proteinuria. Later, the situation is aggravated by polyuria, renal tubular acidosis, as well as hypokalemia and hypophosphatemia of renal origin. Polyuria causes exicosis and hyperthermia, phosphate diabetes causes rickets and dwarfism, potassium deficiency manifests itself in paralysis. In the final stage of the disease, glomerular failure joins tubular failure, and uremia develops.

Diagnosis. Tubular insufficiency, glycosuria, acidosis, hyperaminoaciduria, hyperphosphaturia, accompanied by osteopathy and dwarfism, in the advanced phase of the disease together give a characteristic picture. These changes correspond to the picture of De Toni-Debreu-Fanconi syndrome, which, however, may have a different origin.

At differential diagnosis Detection of cystine crystals in the cornea using a slit lamp or in a biopsy specimen of the lymph glands is crucial.

For treatment prescribe a diet with restriction of methionine and cystine. For the purpose of symptomatic therapy, high doses of vitamin D, the introduction of alkaline solutions and compensation for potassium deficiency, an increased amount of water in the child’s diet and, finally, penicillamine are used.

Forecast bad.

Homocystinuria. The clinical symptoms of the anomaly are characterized by mental retardation of varying degrees, ectopia of the lenses, and blond hair attracts attention. The content of methionine and homocystine in the blood is increased, with the help of special methods Homocystine is detected in the urine.

Treatment- a diet poor in methionine, but it is not very effective.
Women's magazine www.

This is a special, very large group of diseases, the detection and treatment of which is currently very actual problem due to their wide distribution and severe violations physical and intellectual development of sick children. Tests to make a correct diagnosis are usually very complex and expensive. They can only be carried out in large specialized centers. Therefore, a special contingent of children has been identified for whom these studies need to be performed. These children include:

1. children who have a combination of mental retardation and visual impairment;
2. children who have mental retardation and periodically experience seizures;
3. children who have had changes in the color and odor of their urine since birth;
4. children whose mental retardation is combined with various skin lesions.

Below are the main diseases caused by disorders of amino acid metabolism in the body.

Phenylketonuria in children

Phenylketonuria is associated with a violation of the metabolism of amino acids, which are part of the thyroid and adrenal hormones. As a result, the substance phenylalanine is formed in excess, which accumulates in the body and causes disorders associated mainly with damage to the brain and spinal cord. Although the disease is very common, it is almost never found among blacks and Jews. Girls and boys get sick equally often.

Very often, a sick child is born to completely healthy parents. This is due to the fact that the mother and father of the child, without knowing it, are carriers of the affected gene. The likelihood of a sick child appearing in a family where marriages take place between relatives increases very sharply.

Signs of phenylketonuria

They do not appear immediately after birth. Until 2-6 months of age, the child gives the impression of being quite healthy. Upon reaching the above age, when foods containing a “forbidden” amino acid appear in the diet, the child’s parents begin to notice that he has become lethargic, his physical activity, interest in toys and the people around me began to disappear. In some cases, the child, on the contrary, becomes restless, aggressive, often feels sick and vomits, and his skin becomes damaged. Subsequently, convulsive seizures occur. After the sixth month of life, a lag in physical and mental development becomes noticeable, and later there is a decrease in intelligence up to profound mental retardation, which is observed in more than half of all patients. There are, however, known cases of the disease progressing with preservation of normal intelligence. This fact is interpreted by experts as a consequence of the fact that disturbances in several different genes are responsible for the development of the disease, therefore the degree of severity of its symptoms can be very diverse. The picture of various neurological disorders in the disease is very rich.

The child’s physical development also suffers, but not as much; the body length is slightly reduced or normal. A slight decrease in the size of the head due to impaired growth of the skull bones is very typical; teeth in such children begin to erupt at a very late age. There are often malformations of the skeleton and internal organs. Very late, the child learns basic motor skills: crawling, sitting, standing. Subsequently, the sick child has a very peculiar body position and gait. When walking, his legs are widely spaced and slightly bent in knee joints, the head and shoulders are lowered. The steps are very small, the child sways from side to side. The position of a sick child when sitting is called the “tailor's position” - his legs are tucked towards the body as a result of increased muscle tension.

The appearance of a sick child is also very characteristic. His hair and skin are very light in color, as his body contains virtually no pigments. The eyes are light blue. Harmful metabolic products are released along with urine, resulting in a peculiar, so-called “mouse” odor emanating from the child. Some patients develop seizures that resemble those of epilepsy. However, at a later age they disappear completely. In general, the spectrum of neurological disorders in phenylketonuria is very wide.

The most common symptoms observed are incoordination of movements, involuntary obsessive movements, shaking of fingers, convulsions in the various groups oh the muscles, their trembling. Reflexes in the arms and legs are significantly increased, and sometimes reflexes appear that are not normally observed. When the skin is irritated, a bright, long-lasting red or white color appears on it. The child often sweats, the tips of his fingers and toes are bluish in color. Very typical for phenylketonuria are neurological disorders, known clinically as “Salaam seizures.” They manifest themselves in the form of periodic nods and bows, during which the child spreads his arms to the sides. During such attacks, the likelihood of injury is very high.

Numerous lesions are observed on the child’s skin, since due to the lack of pigments it is very vulnerable to the effects of sun rays. Lesions occur in the form of eczema, dermatitis, and various rashes often appear. Violations of internal organs are detected only in cases where there are congenital malformations of their development. Blood pressure in most cases is at very low values. The function of the gastrointestinal tract is often disrupted, and constipation occurs.

The severity of these manifestations directly related to the degree of metabolic disorder. Taken together, these signs are revealed only when the corresponding enzymes are completely absent in the body. With partial disruption of the enzymes, the manifestations of the disease are very diverse. As a rule, disorders of the child’s mental and physical development, neurological disorders and development are combined to varying degrees. characteristic manifestations after eating a meal containing large quantities phenylalanine. There may be no manifestations at all, while the results of biochemical tests indicate the presence of a disease in the child.

These are the main manifestations of the form of the disease known as phenylketonuria type 1. In the second type of disease, the lag in the child’s intellectual development is much more pronounced, convulsive seizures often occur, the child is constantly restless, very excitable, and aggressive. Reflexes in the arms and legs are greatly increased, muscle tension is impaired, and complete paralysis of the muscles of the arms and legs occurs. The disease develops very quickly, and upon reaching the age of 2-3 years, the child dies.

There is also a type of disease of the third type, which in its characteristics is very similar to the second type, only much more severe mental retardation is revealed, a significant reduction in the size of the skull, and movements in the muscles of the arms and legs are more impaired.

In diagnosing the disease, various lab tests, especially the determination of phenylalanine levels in the blood. Various methods of genetic research are now being increasingly used.

Treatment of phenylketonuria in children

Consists of preventing complications associated with the disease. Full compensation for impaired metabolic processes is possible only if the correct diagnosis is made and adequate treatment is started in the shortest possible time, preferably before the birth of the child. From the very first days of life, all foods containing the “forbidden” amino acid are excluded from the child’s diet.

Only this event can achieve positive result and further normal development child. The diet must be followed for a very long time, usually at least 10 years.

All foods rich in protein substances are completely excluded from the child’s daily diet: meat, fish, sausages, eggs, cottage cheese, baked goods, cereals, legumes, nuts, chocolate, etc. Dairy products, vegetables and fruits are allowed, but only in small quantities and taking into account the phenylalanine they contain.

It should be borne in mind that this amino acid is still essential in the body and the minimum requirements for it must be fully satisfied, otherwise it will lead to even more profound disturbances in the child’s development than the disease itself. Since most foods are contraindicated for a child, for a very long time he is doomed to eat only special products, produced both abroad and in Russia. From the first days of a child’s life, it is forbidden to breastfeed; he should receive only formulas specially designed for these patients.

Diet for older children should only be compiled by a medical specialist. This takes into account not only the amount of phenylalanine in the product, but also the child’s age, height, weight, individual nutritional and energy needs.

Proteins enter the child’s body almost exclusively as part of the above specialized food products. The need for fats is satisfied mainly by creamy and vegetable oils. Easier to provide required amount carbohydrates. For this purpose, the child is allowed to eat various fruits, vegetables, juices, sugar, and foods containing starch. Minerals and microelements enter the body almost exclusively through specialized products.

It should be remembered that their taste and smell can lead to a decrease in the child’s appetite. Some children develop nausea, vomiting, and further child is capricious and refuses feedings. In these cases, it is possible to exclude the mixture from the diet for a short period of time. The baby's diet becomes much more varied after he reaches three months of life, when he is allowed to give fruit juices, after half a month, fruit puree is introduced. In another month, the time for introducing the first complementary foods in the form of vegetable puree or canned food, but without dairy products, is approaching. At six months, a child can already eat porridge, but made from pureed sago or protein-free grains, jelly. Then the diet is expanded by introducing mousses.

In sick children in the second year of life, nutrition is very significantly different from that of healthy ones. IN daily ration the main place belongs to various vegetables and fruits. Special protein-free diets are used, which include protein-free pasta, sago, protein-free cereals, corn starch, vegetable margarine, and sour cream. Among products containing sugar, honey, jam, and jam are allowed.

If you follow an appropriate diet, constant monitoring of phenylalanine levels in the blood is a necessary condition. If it increases, dietary recommendations need to be revised. When a disease is detected and its therapy has just begun, such studies must be carried out at least once a week, and in the future, when the child’s condition normalizes, at least once a month. When the child reaches an older age and his condition is stable, laboratory tests can be performed less frequently.

The diet can be gradually discontinued only when the child reaches the age of ten years. Subsequently, all these children are under the supervision of appropriate specialists in the clinic. Their mental and physical development is periodically assessed.

In addition to dietary recommendations, the child is prescribed medication, which includes calcium, phosphorus, iron, vitamins, especially group B, and drugs that improve the transmission of impulses in the nervous system and improve metabolic processes. A complex of physical therapy is prescribed. Work with a child with signs of mental retardation is carried out with the participation of experienced teachers.

For girls planning to have a pregnancy in the future, dieting is necessary until pregnancy and during it. These activities significantly increase the likelihood of having a healthy baby.

Forecast. It is completely determined by the timeliness of diagnosis and initiation of treatment. The second and third types of the disease are most unfavorable, since in them the diet turns out to be practically ineffective.

Histidinemia

First highlighted in the form independent disease in 1961. The metabolism of the amino acid histidine, which mainly occurs in the skin and liver, is disrupted. The disease can be spread among different groups children with different frequencies.

Causes and mechanism of development of histidinemia

As a result of impaired breakdown of histidine, it accumulates in organs and tissues, mainly causing brain damage. There are several types of the disease, the main ones being:

1) the most common form in which amino acid metabolism is disrupted both in the skin and in the liver;

2) metabolic disorder only in the liver while it is preserved in the skin. The disease in this case occurs in a milder form, since the metabolism is partially preserved;

3) incomplete metabolic disorder in the liver and skin. The disease is also relatively mild.

Signs of histidinemia

The first signs of the disease may appear at different ages. They can occur both in a newborn child and during puberty. The disease is very diverse in its manifestations. The child may have a very profound mental retardation, but there may be no manifestations and may not develop in the future. Mental development disorders are detected in a child at a very early age. They manifest themselves in the form of seizures, loss of motor skills, and the child ceases to show interest in toys and people around him. In the future, mental retardation is always observed. It can be expressed to an insignificant extent, or it can reach almost extreme values. Mental disorders manifest themselves in the fact that the child very often experiences mood swings, most often he is excited and aggressive, his behavior and ability to concentrate on any subject are impaired. Most patients have speech impairment, often even with normal mental development.

It is characteristic that among sick children, fair-haired children with blue eyes are more common than dark ones with brown eyes. Therefore, doctors have difficulty differentiating the disease from phenylketonuria.

Main additional methods Biochemical laboratory tests help in diagnosis. Diagnosis is possible before the baby is born.

Treatment of histidinemia

As with other diseases associated with metabolic disorders, the most important treatment method for histidinemia is diet therapy. From birth, all foods containing the amino acid histidine are excluded from the diet. But since this substance is indispensable for child's body, then the minimum need for it must still be satisfied.

Fortunately, a product that contains small amounts of histidine and is recommended for infants is mother's milk. If this is not available, you can give special formulas for feeding, mare's milk and soy milk. Fruits and vegetables mainly contain carbohydrates, so they are “safe” foods and can be given in the same way as to healthy children. Vegetables are preferred as the first additional dish for a child. In the second half of life, when the child begins to be given meat products, sick children should receive them in very limited quantities. The correctness of the diet is assessed by the child’s well-being and laboratory test results.

Products such as beef, chicken, eggs, etc. are especially undesirable in a child’s diet. cow's milk, cottage cheese, cheese, peas, barley, rye, Wheat flour, rice.

Under the influence of diet therapy, seizures very quickly cease to bother the child. But speech disorders and mental retardation are not corrected in this way.

Treatment with medications is also possible, but it does not eliminate the cause of the disease, affecting only one or another of its manifestations.

The prognosis in most cases is favorable and is determined by timely diagnosis and treatment.

Hartnup disease

Opened in 1956. Associated with impaired absorption of the amino acid tryptophan in the intestine. It is quite widespread, but does not appear in all patients.

Signs of Hartnup's disease

First of all, the lesions attract attention skin, similar to those with a deficiency of B vitamins. Often occur allergic lesions skin to exposure to sunlight. There are a wide variety of disorders of the nervous system. There is twitching of the eyeballs, trembling of the fingers when working with small objects, disturbances in the normal tension of the muscles of the arms and legs, movements in them, coordination of movements associated with damage to the cerebellum.

When making a diagnosis, they are guided by the data of laboratory tests: biochemical analysis of blood and urine.

Treatment of Hartnup's disease

Treatment consists mainly of a therapeutic diet. The amount of protein-containing foods in a child's diet should be limited. Increase the amount of fruit consumed. Medicinal methods include the administration of vitamin preparations of various groups. It is necessary to protect the child's skin from direct sunlight.