Genetic disease progeria. Premature aging of the human body - progeria disease (symptoms, causes, treatment)
It can develop at the genetic level. This is progeria disease. Factors unrelated to genes can also influence the occurrence of the condition.
Progeria
Premature aging syndrome is detected extremely rarely. This fatal condition develops only in children. Premature aging syndrome affects approximately one child out of four to eight million newborns. The likelihood of developing the disease is the same in both girls and boys.
Newborn babies diagnosed with premature aging syndrome appear quite healthy. However, once they reach ten to twenty-four months of age, they experience symptoms of progeria.
Among the main signs of the disease it is necessary to note:
A sharp slowdown in growth;
Baldness;
Weight loss;
Stiffness in the joints;
Generalized atherosclerosis.
Despite the fact that premature aging syndrome can be detected in children belonging to different ethnic groups, the patients are surprisingly similar. As a rule, patients rarely live more than twenty years. Average duration The lifespan of such patients is about thirteen years.
Children with progeria are genetically susceptible to premature, progressive heart disease. In almost all cases, death occurs precisely as a result of these diseases. Complications of cardiovascular origin include stroke, hypertension, and angina.
Premature aging non-genetic origin
Almost everyone manages to come to terms with natural aging, which corresponds to old age. However, when premature aging sets in, the condition becomes a serious problem. Women react very painfully to the development of this condition.
Under the influence of certain factors, premature development first appears, then internal systems and organs. As a result, the actual age of many people is often much less than their biological age.
Early skin aging manifests itself in different ways. As a rule, the cover becomes wrinkled, dry, and swelling of the lower and corners of the mouth appears.
The main reasons for the development of the condition primarily include lifestyle, diseases, climate, nutrition, as well as the condition environment.
Among the types of skin aging, photoaging is also distinguished. The condition develops as a result of insufficient hydration and excess sun exposure. It should be noted that it is impossible to replenish the moisture concentration in the skin by simply drinking a large volume of liquid. For this it is necessary to use special means, the properties of which include the ability to retain water molecules.
One of the destructive factors is smoking. It is known to constrict blood vessels, depriving the body of oxygen. As a result, they do not reach the upper skin layer nutrients, it begins to collapse, succumbing to the influence free radicals.
The penetration of toxins can paralyze important functions body, which, in turn, will provoke a deficiency necessary products in the skin.
Great importance specialists pay attention to vitamins. It is necessary to remember the correct balanced diet containing healthy foods.
Psycho-emotional factors also influence the condition of the skin. In modern, often stressful, life, the body is depleted very quickly. In this case, it is necessary to pay attention to the daily routine, control work time and rest periods.
Thus, it is possible to prevent early aging not only of the skin, but also of the entire body.
Progeria (Hutchinson-Gilford syndrome) is a rare pathology caused by a mutation in the gene responsible for protein synthesis. With this pathology, skin changes appear and internal organs that are caused by premature aging.
Childhood progeria, symptoms of which appear from the age of 2 years, causes premature aging: patients live on average up to 13 years and die from atherosclerosis and related diseases -,. Despite the genetic nature of the disease, it is not inherited.
The adult form - Werner syndrome - is a genetic pathology, inherited, begins after 18 years, is characterized by early aging, development of diseases of old age: , . Leads to fatal outcome.
Causes
Hutchinson-Gilford syndrome is a consequence of a mutation, a change in gene structure that occurs spontaneously or under the influence external factors. The carrier of human heredity is the DNA molecule. A gene consists of amino acids connected to each other in a strict sequence. Changes in the composition of the polypeptide chain lead to genetic diseases.
With progeria occur structural changes the gene responsible for the synthesis of the lamin protein. The amino acid cytisine is replaced by thymine. Pathological lamin is called progerin, the accumulation of which leads to premature cell death. Molecular changes lead to processes similar to natural aging.
Adult progeria is also a consequence of a gene mutation. The synthesis of the enzyme responsible for DNA functioning is disrupted. The resulting damage to the genetic apparatus causes premature aging of somatic cells.
Symptoms
Children's progeria symptoms have the following:
- small stature;
- lack of subcutaneous tissue;
- dilated vein under the skin;
- disproportionately large skull;
- lack of hair on the head;
- poor physical development;
- big eyes;
- dental defects;
- “keeled chest”;
- high voice.
Despite the lag in physical development, children with Hutchinson-Gilford syndrome are intellectually developed and do not lag behind their peers in mental development. Childhood progeria is accompanied by the progression of atherosclerosis from the age of 5 and an increase in cardiac pathology - noises appear on auscultation, symptoms of myocardial hypertrophy. Cardiac diseases– the most common reason of death.
Cases of progeria in adults, that is, Werner syndrome, are characterized by the following conditions:
- early gray hair and baldness;
- the appearance of senile wrinkles at a young age;
- pigmentation, dry skin;
- fibrous compactions in the subcutaneous tissue;
- the voice becomes dull.
Progeria is the cause of infertility in men and women. On late stages diseases appear on the legs. Because of muscle atrophy limbs become thinner, joint contractures develop. The “rider pose” is characteristic due to the half-bent arms. The hands become deformed, the nails turn yellow and take on the appearance of “watch glasses.”
X-rays show osteoporosis and lime deposits in the periarticular tissues, ligamentous apparatus joints. Progeria in adults is often accompanied by benign tumors various localizations, endocrine diseases, . In 8-12% there are malignant tumors. Therefore, progeria symptoms are often vague.
Treatment
Hutchinson-Gilford syndrome is a fatal disease that always ends in death. There is no etiotropic treatment that eliminates the cause of the pathology. Atherosclerosis leads to death, in which inner wall Cholesterol is deposited in the vessels, narrowing the lumen of the arteries, and blood flow is disrupted. Myocardial infarction develops. Atherosclerotic plaques cause formation, which can break away from the vessel wall and cause disorders cerebral circulation, stroke.
Treatment of progeria is aimed at reducing the manifestations of atherosclerosis, includes a diet with low content animal fats, rich in protein products: lean meat, fish, cottage cheese. Drug therapy involves the use of statins - drugs that lower blood cholesterol levels:
- Atorvastatin Pfizer;
- "Lipofen";
- "Rosuvastatin Sandoz";
- "Simvastatin";
- "Epadol-neo."
Drugs in this group reduce the concentration of cholesterol and affect the content of lipids in the blood.
With progeria, constant monitoring of the condition is necessary of cardio-vascular system. To prevent and treat heart diseases, medications are used that reduce blood clotting and have antiplatelet properties:
- "Cardiomagnyl";
- "Warfarin Orion";
- "Heparin";
- "Ipaton."
Growth hormone and physiotherapeutic procedures are used to restore joint function. Baby teeth are removed because progeria in children leads to impaired growth.
Drugs have appeared that prolong the life of patients with progeria, and with them the hope that with the development genetic research, it will be possible to cure a disease that was considered fatal.
Intensive study of genetic pathology in Russia and around the world began in the 21st century. Researchers have found that progerin accumulates in small amounts in healthy body, and its content in cells increases with age. Hutchinson-Gilford syndrome and natural aging have common reasons. With development medical science It will become possible not only to heal serious disease, but also to fight old age.
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Diseases with similar symptoms:
Hyperplasia of the adrenal cortex - pathological condition, in which there is a rapid multiplication of the tissues that make up these glands. As a result, the organ increases in size and its functioning is impaired. The disease is diagnosed in both adult men and women and young children. It is worth noting that the most common form of pathology is congenital hyperplasia adrenal cortex. In any case, the disease is quite dangerous, so when its first symptoms appear, you should immediately contact medical institution for a comprehensive examination and appointment effective method therapy.
Progeria translated from ancient Greek means old man. It is a rare genetic disease in which irreversible changes occur in the body, leading to premature aging. There is childhood progeria, called Hutchinson-Gilford syndrome, and adult progeria, known as Werner syndrome.
Mutations in the LMNA gene lead to childhood progeria syndrome. It is this gene that produces the protein lamin, which helps retain the cell nucleus. Scientists believe that a defective lamin protein leads to instability of cell nuclei, which contributes to early aging.
At birth, children with this syndrome appear healthy in appearance and physical appearance. The disease begins to manifest itself at the age of 1.5-2 years. This is expressed by loss of hair and weight, protruding veins are observed, and wrinkled skin is formed. In addition, negative processes are accompanied by complications more common to older people: stroke, cardiovascular diseases, osteoporosis, joint stiffness, generalized atherosclerosis.
One interesting point is observed with this disease. Despite their different ethnic backgrounds, children with this syndrome are externally similar to each other. The most common cause of progeria from which children die is atherosclerosis, and the age to which they live is 13 years. True, the age range ranges from 8 to 21 years.
Adult progeria, according to many years of observations, begins in adolescence, the range is from 15 to 20 years. Naturally, the disease also affects the life expectancy of patients, which is shortened to 40-50 years. Death occurs due to stroke, myocardial infarction, and malignant tumors. The cause of the disease is still unknown and to this day occupies the minds of scientists around the world.
You should know that progeria is a genetic disease, not hereditary. It turns out that the parents are not carriers of this disease. Scientists suggest that a sporadic mutation occurs either in the sperm or in the egg even before the moment of conception. It is also worth noting that if parents have a child with CSGP, then the probability of having a second child of the same kind is small and amounts to 1 in 4-8 million. There are some progeria syndromes that are passed down through generations, but this is not the case with classic CSGP.
Before illness, both sexes (female and male) and all races exclusively are equal. The disease is quite rare and occurs in only one in 8 million children worldwide. Known on this moment 42 cases of this disease.
Progeria is rare genetic disease, first described by Guilford, which manifests itself as premature aging of the body associated with its underdevelopment. Progeria is classified into childhood, called Hutchinson (Hutchinson)-Gilford syndrome, and adult progeria, called Werner syndrome.
With this disease, there is severe stunting from childhood, changes in skin structure, cachexia, absence of secondary sexual characteristics and hair, underdevelopment of internal organs and the appearance of an old person. Wherein mental condition The patient is age appropriate, the epiphyseal cartilaginous plate closes early, and the body has childlike proportions.
Progeria is an incurable disease and is the cause of serious atherosclerosis, which as a result develops strokes and various types. And in the end, this genetic pathology leads to death, i.e. it is fatal. As a rule, a child can live on average thirteen years, although there are cases with a life expectancy of more than twenty years.
Hutchinson-Gilford infantile progeria
This disease is extremely rare in the ratio of 1:4000000 newborns in the Netherlands and 1:8000000 in the USA. Moreover, the disease affects more boys than girls (1.2:1).
Two forms of Hutchinson-Gilford progeria are considered: classical and non-classical.
Currently, more than one hundred cases of childhood progeria have been described. Moreover, this disease mainly affects children of the white race. Hutchinson-Gilford progeria is characterized by polymorphic lesions. Children with this syndrome appear quite normal at birth. But by a year or two there is a serious lag in growth. Typically, such children are characterized by too short stature and even lower body weight in accordance with their length.
It is typical for children with progeria complete baldness not only the scalp, but also the absence of eyelashes and eyebrows from early age. The skin appears weak and wrinkled as a result of the absolute loss of subcutaneous fat present in the skin. The head is characterized by disproportion of the craniofacial bones, which resemble the face of a bird with a hooked nose, abnormally small lower jaw bulging eyeballs and protruding ears. It is these features, a large bald spot and a small jaw, that give the child the appearance of an old person.
Other clinical manifestations progeria include: irregular and late teething, thin and high-pitched voice, pyriform rib cage and reduced in size collarbones. The limbs are usually thin, and the changed elbows and knee joints Give the sick child a “rider pose.”
In children under one year of age, scleral-like compactions, congenital or acquired, are observed on the buttocks, thighs and lower abdomen. Children with progeria are characterized by hyperpigmentation of the skin, which only intensifies over the years, and hypoplasia of the nails, in which they become yellow, thin and convex, reminiscent of watch glasses. However, starting from the age of five, a widespread form of atherosclerosis develops with extensive damage to the aorta and arteries, especially the mesenteric and coronary ones. And much later, heart murmurs and cardiac hypertrophy appear in the left ventricle. The early occurrence of atherosclerosis in children causes their short life span. But it is considered the main cause of death.
There are known cases of progeria ischemic stroke. In mental development, such children are absolutely no different from healthy children, sometimes even ahead of them. Children with this diagnosis live on average about fourteen years.
In childhood progeria of non-classical form, body length lags slightly behind weight, hair is preserved for a long time, and lipodystrophy progresses much more slowly; a recessive type of inheritance is possible.
baby progeria photo
Progeria causes
Still exact reasons The occurrence of progeria has not been clarified. The presumable etiology of the development of this disease is a metabolic disorder in connective tissue, as a result of the proliferation of fibroblasts through cell division and increased collagen formation with reduced synthesis of glycosaminoglycans. The slow formation of fibroblasts is explained by disturbances in the intercellular substance.
In reasons childhood syndrome Progeria is considered to be a mutation in the LMNA gene, which is responsible for encoding lamin A. This is a protein that makes up one of the layers of the nucleus of the cell membrane.
In many cases, progeria appears sporadically, and in some families it occurs in siblings, especially in consanguineous marriages, and this indicates a possible autosomal recessive type of inheritance. When studying the skin of patients, cells were found that had an impaired ability to repair breaks and damage in DNA, as well as reproduce genetically homogeneous fibroblasts, change the atrophic dermis and epidermis, contributing to the disappearance of subcutaneous tissue.
Adult progeria is characterized by autosomal recessive inheritance with a defective ATP-dependent helicase gene, or WRN. There is a suggestion of a linking chain of disturbances between DNA repair and connective tissue turnover.
It has also been established that Hutchinson-Gilford progeria has disorders in carrier cells that cannot fully get rid of DNA cross-links caused by chemical agents. When diagnosing these cells with this syndrome, it was found that they are not able to fully undergo the division process.
In 1971, Olovnikov suggested that telomeres shorten in the process of cell formation. And in 1992, this was already proven in patients with adult progeria syndrome. An assay that links the Hayflick limit, telomere length, and telomerase enzyme activity allows for the integration of natural process aging with formation clinical symptoms Hutchinson-Gilford progeria infantile. Since this form of progeria is extremely rare, one can only hypothesize about the type of inheritance, which is similar to Cockayne syndrome and is manifested by certain features of premature aging.
There are also statements about Hutchinson-Gilford progeria being an autosomal dominant mutation that arose de novo, i.e. without inheritance. It became an indirect confirmation of the syndrome, which was based on measurements of telomeres in carriers of the disease, their parents and donors.
Progeria symptoms
The clinical picture of childhood progeria is characterized by characteristic premature atherosclerosis, myocardial fibrosis, cerebrovascular accidents, increased lipoproteins and cholesterol levels, prothrombin time in tests, early heart attacks, skeletal abnormalities. In this case, there are pronounced disproportions of the face and skull, underdevelopment of the jaw and teeth, and displacement of the hips. Long Bones with normal cortical structure and progression of peripheral demineralization, they are subject to recurrent pathological fractures.
The joints are characterized by tight mobility, especially the knees with possible contractures of the hip, ankle, elbow and wrist joints. At X-ray studies demineralization is detected near joints with osteoporosis, varus and hallux valgus deformities lower extremities. Tumors and thickening of collagen fibers are also very common.
Werner's syndrome or adult progeria manifests itself from 14 to 18 years and is characterized by stunting, universal graying with parallel progression.
As a rule, progeria syndrome develops after twenty years and is characterized by early baldness, thinning of the skin on the face and limbs, and characteristic pallor. Under too-tight skin, superficial blood vessels, and subcutaneous fatty tissue and the muscles located underneath completely atrophy, so the limbs look disproportionately thin.
Then the skin over the bone protrusions gradually becomes thicker and ulcerates. After thirty years of age, patients with progeria develop cataracts in both eyes, the voice becomes weak, high and hoarse, and visibly affected skin. This manifests itself in the form of sclerocerma-like changes in the limbs and face, ulcers on the legs, calluses on the feet and telangiectasia. Such patients are usually short in stature, with a moon-shaped face, a beak-like nose, like a bird’s, a narrowed mouth opening and a sharply protruding chin, a full body and thin limbs.
In patients with progeria, the functions of the sweat and sebaceous glands. On the protrusions of the bones, general hyperpigmentation appears, and the shape of the nail plates changes. And after various injuries, they appear on the legs and feet. trophic ulcers. In addition to thinning, patients experience significant changes in muscles and bones, calcification, generalized, osteoarthritis with erosions. Such patients have limited finger movements and flexion contracture. Patients with progeria are characterized by bone deformation, as in rheumatoid e, pain in the limbs, flat feet and osteomyelitis.
During X-ray examinations, osteoporosis of bones, heterotopic calcifications of the skin and subcutaneous tissue, ligaments and tendons are detected. Also, cataracts slowly progress and develop, disrupting the activity of the cardiovascular system. In most patients, intelligence decreases.
After forty years to progeria in the background diabetes mellitus, dysfunction of the parathyroid glands and other diseases, almost 10% of patients develop tumor pathologies in the form osteosarcoma, astrocytoma, thyroid adenocarcinoma, and skin.
Death is usually a consequence cardiovascular pathologies and malignant tumors.
At histological analysis Progeria syndrome establishes atrophy of the skin appendages where the eccrine glands are preserved; the dermis is thickened, collagen fibers are hyalinized, and nerve fibers are destroyed.
In patients, the muscles completely atrophy and there is no subcutaneous fat.
The disease is diagnosed based on the clinical symptoms of progeria. If the diagnosis is in doubt, the ability of fibroblasts to multiply in culture is determined (reduced indicator for Werner syndrome). For differential diagnosis Progeria takes into account Hutchinson-Gilford, Rothmund-Thomson syndromes and systemic scleroderma.
Progeria treatment
To date, there is no specific treatment for progeria; it has not yet been developed. Basically, therapy is symptomatic in nature with the prevention of complications after atherosclerosis and the treatment of trophic ulcers.
For an anabolic effect, growth hormone is prescribed, which in some patients increases body weight and length. The entire therapeutic process is carried out by a number of specialists, such as an endocrinologist, therapist, cardiologist, oncologist and others, depending on the prevailing symptoms.
But in 2006, US researchers noted progression in the treatment of progeria, as incurable disease. They introduced a farnesyltransferase inhibitor into the culture of damaged fibroblasts, which had previously been tested on cancer patients. And this process returned to aging cells normal shape. This drug was well tolerated, so there is now hope that in the future it will be possible to use it to prevent progeria in childhood.
The effectiveness of Lonafarnib (farnesyl transferase inhibitor) is to increase the amount of fat under the skin, body weight, bone mineralization, which will ultimately reduce fractures.
But, nevertheless, this disease is still characterized by unfavorable prognosis. On average, patients with progeria live to the age of thirteen, dying from hemorrhages and heart attacks.
This is an extremely rare genetic disease that accelerates the aging process by approximately 8-10 times. Simply put, a child ages 10-15 years in one year. Children with progeria appear normal for 6 to 12 months after birth. After this, they develop symptoms characteristic of old age: wrinkled skin, baldness, brittle bones and atherosclerosis. An eight-year-old child looks 80 years old - with dry, wrinkled skin, a bald head...
Features of such patients include dwarf stature, low weight (usually not exceeding 15-20 kg), excessively thin skin, poor joint mobility, underdeveloped chin, small face in comparison with the size of the head, which gives a person bird-like features. Due to the loss of subcutaneous fat, all blood vessels are visible. The voice is usually high. Mental development appropriate for age. And all these sick children are strikingly similar to each other.
Progeria also causes other problems: in children, for example, a second row of teeth appears in the mouth, and the skin becomes very pale, almost transparent.
These children usually die at the age of 13-14 simply “of old age.” More precisely, from those diseases that are characteristic of old age. For example, they can die from a simple heart attack. And, as a rule, after several heart attacks and strokes against the background of progressive atherosclerosis, cataracts, glaucoma, complete loss of teeth, etc. Only a few live to 20 years or longer. People call this disease “canine old age.”
There are now about 60 known cases of progeria in people around the world. Of these, 14 people live in the United States, 5 in Russia, and the rest in Europe.
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Until recently, doctors were unable to determine the cause of the disease. And only recently, American researchers discovered that the cause of “childhood old age” is a single mutation. Progeria is caused by a mutated form of the LMNA gene. According to the director of the National Genome Research Institute, Francis Collins, who led the study, the disease is not hereditary. A point mutation—when only one nucleotide is changed in a DNA molecule—occurs anew in every patient. Genetic mutation in the protein Lamin A causes accelerated aging of the body. And the young man - with his large protruding ears, bulging eyes and swollen veins on his bald skull - turns into a one hundred and sixteen year old man.
IN Lately some of these patients had a ghostly hope of recovery. American scientists have begun a clinical trial of a drug against Hudchinson-Gilford syndrome. If the tests can be brought to a successful conclusion, the victory over progeria will be a victory for people doing everything to save their children from imminent inevitable death.
Researchers in their work came across a drug - a farnisyltransferase inhibitor; it turned out to be able to block the production of this protein and, at least, stop the development pathological processes, and even reverse some of them.
However, there is a problem in identifying such patients. There are few of them and they are scattered all over the world. The initiative group took on a huge amount of work to find them. Patients live in different countries, you need to get their consent, the consent of their parents. It is finally necessary to bring them, if such consent is obtained, to Boston (tests are being carried out at Children's Hospital Boston). And the life of such children is short. It is believed that the maximum age to which a patient with progeria can live is 27 years But even this is a rare case.
Hussein Khan and his family are unique in their own way: this is the only case known to science when more than one family member suffers from progeria. And thanks to this family, scientists were able to make a real breakthrough in understanding the nature of the disease. Hana's husband and wife are cousins. Neither of them has progeria, nor do their two children, 14-year-old Sangeeta and two-year-old Gulavsa. Their 19-year-old daughter Rehena and two sons: 7-year-old Ali Hussein and 17-year-old Ikramul suffer from this disease. None of them have virtually any chance of living to 25.
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Adult progeria manifests itself in the following symptoms. Slowly developing juvenile cataract. The skin of the feet, legs, to a lesser extent, hands and forearms, as well as the face, gradually becomes thinner, the subcutaneous tissue and muscles in these areas atrophy. On lower limbs 90% of patients develop trophic ulcers, hyperkeratosis and nail dystrophy. Atrophy of the facial skin ends with the formation of a beak-shaped nose (“bird nose”), narrowing of the mouth and a sharpening of the chin, reminiscent of a “scleroderma mask.” From endocrine disorders hypogenitalism is noted, late appearance or absence of secondary sexual characteristics, dysfunction of the upper and lower parathyroid glands(violation calcium metabolism), thyroid gland(exophthalmos) and pituitary gland (moon-shaped face, high-pitched voice). Osteoporosis is often observed. Changes in the fingers resemble those seen in sclerodactyly. Most patients with Werner syndrome die before age 40. Trials are currently underway to treat the disease with stem cells.
