The genetic disease of progeria. Premature aging of the human body - progeria disease (symptoms, causes, treatment)
It can develop at the genetic level. This is a progeria disease. Also, factors that are not related to genes can affect the occurrence of the condition.
Progeria
Premature aging syndrome is extremely rare. This fatal character develops only in children. Premature aging syndrome is detected in approximately one child in four to eight million newborns. The likelihood of developing the disease is the same in both girls and boys.
Newborn babies who are diagnosed with premature aging syndrome look quite healthy. However, when they reach the age of ten to twenty-four months, they show symptoms of progeria.
Among the main signs of the disease, it should be noted:
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. The average life expectancy 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 because of these diseases. Among the complications of cardiovascular origin, stroke, hypertension, angina pectoris are detected.
Premature aging of non-genetic origin
With natural aging, corresponding to old age, almost everyone manages to put up with it. 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, first appears premature then internal systems and organs. As a result, often the actual age of many people is much less than the biological age.
Early skin aging manifests itself in different ways. As a rule, the cover becomes wrinkled, dry, swelling of the lower and corners of the mouth appears.
The main reasons for the development of the condition, first of all, include lifestyle, diseases, climate, nutrition, and the state of the environment.
Among the types of skin aging, photoaging is also distinguished. The condition develops as a result of insufficient moisture and an excess of sun exposure. At the same time, it should be noted that it is impossible to replenish the concentration of moisture in the skin simply by consuming a large amount of liquid. For it, it is necessary to use special means, in the properties of which - the ability to retain water molecules.
One of the destructive factors is smoking. As you know, it contributes to vasoconstriction, depriving the body of oxygen. As a result, nutrients do not reach the upper skin layer, it begins to break down, succumbing to free radicals.
The penetration of toxins can paralyze important functions of the body, which, in turn, will provoke a lack of necessary products in the skin.
Specialists pay great attention to vitamins. You should remember about the right, balanced diet containing healthy foods.
Psycho-emotional factors also influence the condition of the skin. In the conditions of modern, often stressful, life, the body is depleted very quickly. In this case, it is necessary to pay attention to the daily routine, control working hours and rest periods.
Thus, it is possible to prevent early aging not only of the skin, but of the whole organism.
Progeria (Hutchinson-Gilford syndrome) is a rare disease caused by a mutation in the gene responsible for protein synthesis. With this pathology, changes in the skin and internal organs appear, which are caused by premature aging.
Childhood progeria, the 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's syndrome - is a genetic pathology, inherited, begins after 18 years, is characterized by early aging, the development of diseases of the elderly:,. Leads to death.
Causes
Hutchinson-Gilford syndrome is a consequence of a mutation, a change in the structure of a gene that occurs spontaneously or under the influence of 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, structural changes occur in 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 the result of a gene mutation. The synthesis of the enzyme responsible for the work of DNA is disrupted. The resulting damage to the genetic apparatus causes premature aging of somatic cells.
Symptoms
Children's progeria symptoms are as follows:
- small stature;
- lack of subcutaneous tissue;
- an enlarged vein under the skin;
- disproportionately large skull;
- lack of hair on the head;
- poor physical development;
- big eyes;
- teeth 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. Children's progeria is accompanied by the progression of atherosclerosis from the age of 5 and the increase in cardiac pathology - there are noises during auscultation, symptoms of myocardial hypertrophy. Cardiac diseases are the most common cause of death.
Cases of progeria in adults, that is, Werner's 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 seals in the subcutaneous tissue;
- the voice becomes muffled.
Progeria is the cause of infertility in men and women. In the later stages of the disease appear on the legs. Due to muscle atrophy, limbs become thinner, joint contractures develop,. The “horseman posture” is characteristic due to half-bent arms. The hands are deformed, the nails turn yellow, take the form of "watch glasses".
When x-rays, osteoporosis and lime deposits are observed in the periarticular tissues, the ligamentous apparatus of the joints. Adult progeria is often accompanied by benign tumors of various localization, endocrine diseases,. In 8-12% malignant tumors occur. Therefore, progeria symptoms are often blurred.
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 cholesterol is deposited on the inner wall of the vessels, narrowing the lumen of the arteries, and blood flow is disturbed. Develops myocardial infarction. Atherosclerotic plaques cause formation, which can break away from the vessel wall and cause cerebrovascular accidents, stroke.
Treatment of progeria is aimed at reducing the manifestations of atherosclerosis, provides for a diet low in animal fats, rich in protein foods: 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, affect the content of lipids in the blood.
With progeria, constant monitoring of the state of the cardiovascular system is necessary. To prevent and treat heart diseases, drugs are used that reduce blood clotting ability, which have antiplatelet properties:
- "Cardiomagnyl";
- "Warfarin Orion";
- "Heparin";
- "Ipaton".
Growth hormone, physiotherapy procedures are used to restore joint function. Milk teeth are removed, as progeria in children leads to a violation of their growth.
Drugs have appeared that prolong the life of patients with progeria, and with them the hope that with the development of 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 a healthy body, and its content in cells increases with age. Hutchinson-Gilford syndrome and natural aging have common causes. With the development of medical science, it will become possible not only to cure a serious illness, but also to fight old age.
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Progeria in translation from the ancient Greek language means - the old man. It is a rare genetic disease in which irreversible changes occur in the body, leading to premature aging. Children's progeria, called Hutchinson-Gilford syndrome, and adult progeria, known as Werner's syndrome, are distinguished.
Mutations in the LMNA gene result in the syndrome of childhood progeria. It is this gene that produces the lamin protein, which contributes to the retention of the cell nucleus. Scientists believe that the defective protein lamin leads to instability of cell nuclei, which contributes to early aging.
At birth, children with this syndrome appear to be physically and externally healthy. The disease begins to manifest itself at the age of 1.5-2 years. This is expressed by loss of hair and weight, protrusion of veins is observed, wrinkled skin is formed. In addition, negative processes are accompanied by complications more common in older people: stroke, cardiovascular disease, osteoporosis, joint stiffness, generalized atherosclerosis.
With this disease, there is one interesting point. Despite the different ethnicity, children with this syndrome have an outward resemblance 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 long-term observations, begins in adolescence, the range ranges 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, malignant tumors. The reason for the development 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 SHGP, then the probability of having a second child of the same kind is small - 1 in 4-8 million. There are some progeria syndromes that are passed down through the generations, but this is not the case with classic SHGP.
Before the disease, both sexes (female and male) and all exclusively races are equal. The disease is quite rare and occurs worldwide in only one in 8 million children. There are currently 42 known cases of this disease.
Progeria is a rare genetic disease, first described by Gilford, which is manifested by premature aging of the body associated with its underdevelopment. Progeria is classified into childhood, called the Hutchinson (Hutchinson)-Gilford syndrome, and adult - Werner's syndrome.
With this disease, there is a strong lag in growth since childhood, a change in the structure of the skin, cachexia, the absence of secondary sexual characteristics and hair, underdevelopment of internal organs and the appearance of an old person. At the same time, the mental state of the patient corresponds to the age, the epiphyseal cartilaginous plate closes early, and the body has childish proportions.
Progeria is an incurable disease and is the cause of serious atherosclerosis, which as a result develops strokes and various diseases. And in the end, this genetic pathology leads to death, i.e. she 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 Pediatric Progeria
This disease is extremely rare in the ratio of 1:4,000,000 newborns in the Netherlands and 1:8,000,000 in the United States. 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 a hundred cases of childhood progeria have been described. Moreover, this disease mainly affects children of the white race. Hutchinson-Gilford progeria is characterized by a polymorphic lesion. 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 too small in stature and even lower in body weight in accordance with its length.
Children with progeria are characterized by complete baldness not only of the scalp, but also by the absence of eyelashes and eyebrows from an early age. The skin looks weak and wrinkled as a result of the absolute loss of subcutaneous fat, the skin is present. The head is characterized by disproportionate craniofacial bones, which resemble the face of a bird with a hooked nose, an abnormally small lower jaw, bulging eyeballs and protruding ears. It is these features, a large bald head and a small jaw, that give the appearance of a child the appearance of an old man.
Other clinical manifestations of progeria include: irregular and late teething, thin and high voice, pear-shaped chest and reduced collarbones. The limbs are usually thin, and the modified elbow and knee joints give the sick child a "rider posture".
In children up to a year, sclero-like seals, congenital or acquired, are noted on the buttocks, thighs and lower abdomen. Children with progeria are characterized by hyperpigmentation of the skin, which only intensifies with age, and hypoplastic nails, in which they become yellow, thin and convex, resembling watch glasses. However, starting from the age of five, a common form of atherosclerosis develops with a large lesion of the aorta and arteries, especially mesenteric and coronary. And much later, heart murmurs and hypertrophy of the heart appear in the left ventricle. The early occurrence of atherosclerosis in children becomes the reason for their short life. But the main cause of death is considered.
With progeria, cases of ischemic stroke are known. Such children in mental development are absolutely no different from healthy children, sometimes even ahead of them. Children with this diagnosis live on average for about fourteen years.
In children's progeria of a non-classical form, the body length lags slightly behind the mass, the hair remains for a long time, and lipodystrophy progresses much more slowly; recessive inheritance is possible.
baby progeria photo
Progeria causes
Until now, the exact causes of progeria have not been clarified. The presumed etiology of the development of this disease is a metabolic disorder in the connective tissue, as a result of the growth of fibroblasts through cell division and an increase in the formation of collagen with a reduced synthesis of glycosaminoglycans. The slow formation of fibroblasts is explained by disturbances in the intercellular substance.
Mutations in the LMNA gene, which is responsible for encoding lamin A, are considered to be the causes of childhood progeria syndrome. This is a protein that makes up one of the layers of the nucleus of the cell membrane.
In many cases, progeria manifests itself sporadically, and in some families it occurs in siblings, especially in consanguineous marriages, and this indicates a possible autosomal recessive mode of inheritance. When examining the skin of patients, cells were found in which the ability to repair breaks and damage in DNA was impaired, as well as to reproduce genetically homogeneous fibroblasts, change the atrophic dermis and epidermis, which contribute to the disappearance of subcutaneous tissue.
Adult progeria is characterized by autosomal recessive inheritance with a defective ATP-dependent helicase or WRN gene. There is an assumption in the linking chain of disorders between DNA repair and connective tissue turnover.
It has also been found 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 such a syndrome, it was found that they are not able to fully undergo the process of division.
In 1971, Olovnikov suggested that telomeres shortened in the process of cell formation. And in 1992, this was already proven in patients with adult progeria syndrome. The analysis, which links the Hayflick limit, telomere length and telomerase enzyme activity, combines the natural aging process with the formation of the clinical symptoms of Hutchinson-Gilford childhood progeria. Since this form of progeria is extremely rare, one can only hypothesize about the type of inheritance that has similarities with Cockayne's syndrome and is manifested by individual features of premature aging.
There are also statements about the Hutchinson-Gilford progeria belonging to a mutation, autosomal dominant, which arose de novo, i.e. no 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, and skeletal anomalies. 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 progressive peripheral demineralization undergo recurrent pathological fractures.
Joints are characterized by tight mobility, especially knee joints with possible contractures of the hip, ankle, elbow and wrist joints. X-ray studies reveal demineralization near the joints with osteoporosis, varus and valgus deformities of the lower extremities. Tumors and thickening of collagen fibers are also very common.
Werner syndrome or adult progeria appears between 14 and 18 years of age 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. Superficial blood vessels are visible under too stretched skin, and the subcutaneous fatty tissue and muscles located under it completely atrophy, so the limbs look disproportionately thin.
Then the skin over the protrusions of the bones gradually becomes thicker and ulcerates. After thirty years, patients with progeria develop cataracts in both eyes, the voice becomes weak, high and hoarse, the skin is noticeably affected. This manifests itself in the form of sclerocermo-like changes in the limbs and face, ulcers on the legs, calluses on the feet and telangiectasia. Such patients, as a rule, are short in stature, with a moon-shaped face, a beak-like nose, like a bird, 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 are impaired. On the protrusions of the bones, general hyperpigmentation is formed, the shape of the nail plates changes. And after various injuries, trophic ulcers appear on the legs and feet. In addition to thinning, patients have significant changes in muscles and bones, calcification, of a generalized nature, osteoarthritis with erosions. Such patients are limited in the movements of the fingers and flexion contracture. Progeria patients are characterized by bone deformity, as in rheumatoid e, pain in the extremities, flat feet and osteomyelitis.
During X-ray examinations, bone osteoporosis, heterotopic calcifications of the skin and subcutaneous tissue, ligaments and tendons are detected. Also, cataract slowly progresses, develops, disrupting the activity of the cardiovascular system. Most patients have decreased intelligence.
After forty years of progeria on the background of diabetes mellitus, dysfunctions of the parathyroid glands and other diseases, almost 10% of patients develop tumor pathologies in the form of osteogenic sarcoma, astrocytoma, thyroid adenocarcinoma, and skin.
The lethal outcome is usually a consequence of cardiovascular pathologies and malignant tumors.
In the histological analysis of the progeria syndrome, atrophy of the skin appendages is established, where the eccrine glands are preserved; in this case, the dermis has a thickening, collagen fibers are hyalinized, and nerve fibers are destroyed.
In patients, muscles completely atrophy, there is no subcutaneous fat.
The disease is diagnosed on the basis of the clinical symptoms of progeria. If the diagnosis is in doubt, the ability of fibroblasts to multiply in culture is determined (reduced rate for Werner's syndrome). For the differential diagnosis of progeria, Hutchinson-Gilford, Rothmund-Thomson syndromes and systemic scleroderma are taken into account.
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 in the treatment of trophic ulcers,.
For an anabolic effect, STH 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, internist, cardiologist, oncologist and others, depending on the prevailing symptoms.
But in 2006, US researchers noted progress in the treatment of progeria as an incurable disease. They introduced a farnesyl transferase inhibitor into the culture of disturbed fibroblasts, which had previously been tested on cancer patients. And this process returned the aging cells to their normal shape. Such a drug has been well tolerated, so now there is hope that in the future it will be possible to use it to prevent progeria in childhood.
The effectiveness of Lonafarnib (a farnesyl transferase inhibitor) is to increase the amount of fat under the skin, in body weight, bone mineralization, which will ultimately reduce fractures.
But, nevertheless, while this disease is 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 about 8-10 times. Simply put, a child ages 10-15 years in one year. Babies with progeria look normal for 6 to 12 months after birth. After that, 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 ...
Among the features of such patients are dwarf growth, low weight (usually not exceeding 15-20 kg), excessively thin skin, poor joint mobility, an underdeveloped chin, a small face in comparison with the size of the head, which gives the person as if bird features. Due to the loss of subcutaneous fat, all vessels are visible. The voice is usually high. Mental development corresponds to 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 or 14 simply "of old age". More precisely, from those diseases that are characteristic of old age. For example, they can die from a banal 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. In the people this disease is called "dog old age".
Now in the world about 60 cases of people with progeria are known. Of these, 14 people live in the United States, 5 - in Russia, the rest in Europe.
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Until recently, doctors could not determine the cause of the disease. And only recently, American researchers discovered that the cause of "childish old age" is a single mutation. Progeria is caused by a mutated form of the LMNA gene. According to the director of the National Institute for Genome Research Francis Collins (Francis Collins), who led the study, this disease is not hereditary. A point mutation - when only one nucleotide is changed in a DNA molecule - occurs anew in each patient. A genetic mutation in the lamin A protein causes accelerated aging of the body. And the young man - with his big protruding ears, bulging eyes and swollen veins on his bald skull - turns into a hundred and sixteen year old man.
Recently, some of these patients have a illusory hope for recovery. American scientists have begun a clinical trial of a remedy for Hudchinson's Gilford syndrome. If it is possible to bring the trials to a successful conclusion, the victory over progeria will be the victory of people who are doing everything to save their children from imminent death.
Researchers in their work came across a drug - an inhibitor of farnisyltransferase, it turned out to be able to block the production of this protein and, at least, stop the development of pathological processes, and even reverse them somewhat.
However, there is a problem in identifying such patients. They are few and scattered all over the world. The initiative group took on a huge job of finding them. Patients live in different countries, you need to get their consent, the consent of their parents. We should finally bring them, if such consent is obtained, to Boston (trials are taking place at the Children's Hospital of Boston (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 kind: 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 to each other. None of them have progeria, and neither do their two children, 14-year-old Sangita and 2-year-old Gulavsa. This disease affects their 19-year-old daughter Rehena and two sons: 7-year-old Ali Hussein and 17-year-old Ikramul. None of them have any chance of surviving to 25.
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Adult progeria is manifested in the following symptoms. Slow developing juvenile cataract. The skin of the feet, legs, to a lesser extent of the hands and forearms, as well as the face gradually becomes thinner, the subcutaneous base and muscles in these areas atrophy. Trophic ulcers, hyperkeratosis and nail dystrophy occur in 90% of patients on the lower extremities. Atrophy of the skin of the face ends with the formation of a beak-shaped nose ("bird's nose"), narrowing of the oral fissure and sharpening of the chin, resembling a "scleroderma mask". Of the endocrine disorders, hypogenitalism, late appearance or absence of secondary sexual characteristics, dysfunction of the upper and lower parathyroid glands (impaired calcium metabolism), thyroid gland (exophthalmos) and pituitary gland (lunar face, high voice) are noted. Often there is osteoporosis. Changes in the fingers resemble those in sclerodactyly. Most patients with Werner's syndrome die before the age of 40. Trials are currently underway to treat the disease with stem cells.
