Progeria which means premature aging syndrome. Progeria or premature aging syndrome

What is progeria, what are its signs and effects? How is the disease diagnosed and what treatment is available today?

Hutchinson-Gilford Progeria Syndrome (HGS) is a rare, fatal genetic disorder characterized by sudden, accelerated aging in children, affecting one in 8 million children worldwide. The name of the syndrome comes from the Greek word and means "premature aging". Although there are various forms of Progeria, the classic type of Hutchinson-Gilford Progeria Syndrome is named after the physicians who first described the disease, in 1886 Dr. Jonathan Hutchinson and in 1897 Dr. Hastings Guilford.

It is now known that SHGP is caused by a mutation in the LMNA (Lamin) gene. The LMNA gene produces the protein lamin, which holds the cell nucleus. Researchers believe that the defective lamin protein makes cell nuclei unstable. And it is this instability that triggers the process of premature aging.

Children with this syndrome appear healthy at birth, the first physical signs of the disease may appear at the age of one and a half to two years. This cessation of growth, weight and hair loss, protruding veins, wrinkled skin - all this is accompanied by complications more characteristic of older people - joint stiffness, generalized atherosclerosis, osteoporosis, cardiovascular disease, stroke. Children with this condition have a remarkably similar appearance despite their different ethnicity. Most often, children with progeria die of (heart disease) at an average age of thirteen (range from about 8 to 21 years).

There is also "adult" progeria (Werner's syndrome), which begins in adolescence (15-20 years). The life expectancy of patients is reduced to 40-50 years. The most common causes of death are myocardial infarction, stroke and malignant tumors. Scientists cannot determine the exact cause of the development of the disease.

Who is at risk?

Although progeria is a genetic disease, in the classical understanding of the Hutchinson-Gilford syndrome, but not hereditary, i.e. neither parent is either a carrier or affected. Each case is thought to be a sporadic (random) mutation that occurs either in the egg or sperm prior to conception.

The disease affects all races and both sexes equally. If a couple of parents have one child with SHGP, the chance that a second child will be born with the same condition is 1 in 4 to 8 million. There are other progeric syndromes that can be passed down from generation to generation, but not classic SHPS.

How is progeria diagnosed?

Now that this gene mutation has been identified, the Progeria Research Foundation has developed diagnostic testing programs. It is now possible to confirm specific genetic changes or mutations in a gene that lead to SHGP. After an initial clinical assessment (appearance of the child and medical records), a blood sample is taken from the child for testing. The definitive scientific method for diagnosing children is currently being developed. This will result in more accurate and more early diagnosis, which will help ensure that children with this mutation are properly cared for.

What treatments are available for children with progeria?

A common, at first glance, form of psychological state - phobic anxiety, causes cell damage and leads to premature aging.

To date, only a few ways are available to optimize the quality of life of children with Progeria. Treatment includes ongoing care, cardiac care, special nutrition, and physical therapy.

Over the past few years, encouraging research data has been published that describes potential drug treatments for children with progeria. Scientists believe that farnesyl transferase inhibitors (FTIs), originally developed to treat cancer, may reverse the structural abnormalities that cause progeria in children.

Twenty-six children took part in trials of the drug - this is a third of all known cases of progeria. Children who took the drug showed a 50% increase in annual weight gain. The children also improved bone density to normal levels and a 35% reduction in arterial stiffness, which is associated with a high risk of heart attack. The researchers emphasize that thanks to the new development, damage to blood vessels is not only reduced, but also partially restored over a period.

No matter how incredible it may seem, but progeria really triggers premature aging mechanisms in a young body. Officially, the disease was named after the scientists who first described and studied the pathology: in children it is Hutchinson-Gilford syndrome, in adults it is Werner syndrome.

Progeria is several times more common in boys than in girls. On average, patients live from 10 to 13 years (in exceptional cases up to 20): a fatal disease, unfortunately, does not give a chance for recovery and long life. Such children noticeably lag behind in physical development from healthy peers, but this is not all the “charms” of progeria. Severe exhaustion of the body, violation of the structure of the skin, the absence of secondary signs of sexual development and hair, underdeveloped internal organs and the appearance of the old man as a whole - this is the burden that falls on the shoulders of the unfortunate child.

In mental development, the child is absolutely adequate, his body retains childish proportions, but at the same time, the epiphyseal cartilage quickly overgrows and an epiphyseal line appears in its place - everything is like in an adult. Rapidly maturing children are forced to face far from childish problems associated with progeria: atherosclerosis, stroke, various heart diseases.

Causes of pathology

The real face of the "enemy" experts, alas, have not yet thoroughly examined. As a result of long-term research, scientists were able to find out that the pathology is most likely based on a mutation of the lamin gene (LMNA), which is directly related to the process of cell division. A failure in the genetic system deprives cells of resistance and triggers unforeseen mechanisms of aging in the body.

Progeria, unlike many other diseases of genetic etiology, is not inherited, that is, it appears absolutely by chance, and none of the parents of a sick child can be called a carrier of pathology.

Symptoms of the disease

Immediately after birth, children carrying the deadly progeria gene are indistinguishable from healthy babies. Already by the first year of life, numerous symptoms of the disease make themselves felt in full. Among them:

1. Visible lack of body weight, very short stature.
2. Absence of hair on the head, eyelashes and eyebrows.
3. Lack of subcutaneous fat and lack of tone in the skin - it is weak and wrinkled.
4. Bluish tinge of the skin.
5. Skin hyperpigmentation.
6. Prominent veins under the skin on the head.
7. Disproportionate development of the bones of the face and skull, a small lower jaw, bulging eyes and protruding auricles, a hooked nose - the child has a "bird" facial expression. It is this set of specific features that makes him look like an old man.
8. Late appearance of teeth that deteriorate quickly.
9. The voice is piercing and high.
10. Pear-shaped chest, small clavicles, "tight" knee and elbow joints, which, due to poor mobility, force the patient to be in the "rider" position.
11. Yellow bulging nails - "hour glass".
12. Sclera-like formations on the skin of the buttocks, thighs and lower abdomen.

After a child suffering from progeria celebrates his fifth birthday, inexorable development processes begin in his body, in which the aorta, mesenteric and coronary arteries are especially affected. Against the background of these disorders, the appearance of heart murmurs and left ventricular hypertrophy is noted. The complex effect of these disorders on the body is considered one of the reasons for the short life of patients with progeria. The main factor in the sudden death of patients is also called ischemic stroke.

Progeria in adults

The disease can suddenly overtake an adult person at the age of 14-15 to 18 years. The patient begins to lose weight, lag behind in growth, turn gray and gradually go bald (progressive alopecia). The skin of a person with progeria becomes thinner, loses all its colors, acquiring an unhealthy pale shade. Under it, a network of blood vessels is clearly visible, subcutaneous fat and muscles completely atrophy, so the arms and legs seem very thin.

In patients who have crossed the 30-year mark, both eyeballs are affected, the voice weakens, the skin over the protrusions of the bones becomes coarse and covered with ulcers. Progeria sufferers look the same: short stature, a moon-shaped face, a nose resembling a bird's beak, a narrow mouth, a sharply protruding chin, a dense body and thin, dry limbs, disfigured by numerous age spots. The disease unceremoniously interferes with various systems of the body: the work of the sweat and sebaceous glands is disrupted, the normal activity of the cardiovascular system is distorted, the body suffers from calcification, osteoporosis and erosive osteoarthritis. In contrast to small patients, in adults, the disease also adversely affects intellectual abilities.

About 10% of patients by the age of forty face such terrible diseases as sarcoma, astrocytoma, melanoma. Oncology develops against the background of diabetes mellitus and impaired functions of the parathyroid glands. The immediate cause of death in patients with progeria in most cases are malignant tumors and cardiovascular pathologies.

Diagnosis of the disease

The external symptomatic manifestations of the pathology are so vivid and eloquent that the disease is diagnosed based on the data of the clinical picture.

Treatment of the disease

MirSovetov is forced to admit that, unfortunately, there is no panacea for progeria. All methods of treatment that are used today are also not always effective. However, doctors do everything that depends on them. So, all patients are under regular medical supervision, because with the help of monitoring the state of the cardiovascular system, it is possible to detect the development of a complication of a particular "heart" disease in time.

All methods of treatment pursue a single, but vital goal - to "freeze" the disease, not allow it to worsen and alleviate the patient's condition, as far as the possibilities of modern medicine allow. How can experts help?

1. The use of minimum doses that can protect a person from a possible heart attack or.
2. The use of other medicines that are prescribed individually, based on the condition of each individual patient. For example, drugs from the statin group reduce elevated blood cholesterol levels, and so-called anticoagulants block the formation of blood clots. Growth hormone is often used, which "increases" height and weight.
3. The use of physiotherapy procedures that develop joints that bend with difficulty, allowing a person to remain active. And what could be more important for little patients?
4. Removal of milk teeth. The specificity of the disease contributes to the early eruption of permanent teeth in children, while milk teeth deteriorate very quickly, so they must be removed in a timely manner.

Prevention of the disease has not yet been developed.

“Looking at this flabby face, sunken eyes and flabby skin, you can hardly think that this is a child. However, this is so. The story of 5-year-old Bayezid Hossein, who lives in southern Bangladesh, is known to many. The boy suffers from a rare genetic disease - progeria, in which the body and body age eight times faster than normal. It all starts with muscle atrophy, dystrophic processes in the teeth, hair and nails, changes in the bone and joint apparatus, this process ends with atherosclerosis, stroke and malignant tumors. As we can see, progeria has not encouraging symptoms at all, which develop into deadly diseases. Therefore, such patients are always waiting for a fatal outcome. But can they ease their pain and even prolong their lives? Or, perhaps, scientists are already on the verge of creating a cure for this disorder? We will tell in today's article.

Hutchinson syndrome in a child, Wikimedia

Children's progeria, or Hutchinson (Hutchinson)-Gilford syndrome

For the first time, an ailment in which the body ages prematurely was identified and described in 1889 by J. Hutchinson and independently in 1897 by H. Gilford. In their honor, they named the syndrome, which manifests itself in childhood.

Despite the fact that progeria is a rare disease (only one in 7 million newborns is diagnosed), more than 150 cases have already been recorded in the entire history of observations of this disease in the world. At birth, children look absolutely healthy, the first signs of accelerated aging begin to appear in babies at the age of 10-24 months.

The cause of the disease is a mutation of the LMNA gene, it produces the prelamin A protein, which forms a unique protein network - the inner frame of the nuclear envelope. As a result, the cells lose their ability to divide normally.

Examining patients, geneticists also found violations in the repair (restorative function) of DNA, cloning of fibroblasts (the main cells of connective tissue) and the disappearance of subcutaneous tissue.

As a rule, progeria is a non-hereditary disease, and cases of its development are isolated, but there are exceptions. This mutation has been reported in several families in sibling children. - offspring of closely related parents. And this indicates the possibility of an autosomal recessive type of inheritance, which manifests itself already in people in adulthood. By the way, this happens to one in 200,000 people.

Progeria in adults, or Werner's syndrome

Back in 1904, the German physician Otto Werner noticed dramatic changes in appearance and condition in people aged 14-18. He discovered the syndrome, which is associated with a sharp loss in weight, stunting, the appearance of gray hair and gradual baldness.

All these transformations of a teenager into an old man are associated with a defect in the WRN gene (ATP-dependent helicase gene). The role of the WRN protein it produces is to maintain genomic stability and preserve the structure and integrity of human DNA. Mutation over time disrupts gene expression, DNA loses the ability to restore, which is the cause of premature aging.

Unlike small patients who do not lag behind, and somewhere even surpass their peers in mental development, adults have the opposite effect, because. progeria begins to adversely affect their intellectual abilities.

About 10% of patients by the age of forty face such terrible diseases as sarcoma, breast cancer, astrocytoma, melanoma. Oncology develops against the background of diabetes mellitus and dysfunction of the parathyroid glands. Therefore, the average life expectancy of people with Werner's syndrome is 30-40 years.

The world's first treatment for progeria. American scientists have tested a unique drug

Progeria is currently considered an incurable disease. The life of people with Hutchinson (Hutchinson)-Gilford syndrome ends at the age of 7-13 years, but there are isolated cases when patients lived to 20, and even 27 years. And all this thanks to some kind of treatment.

However, specialists from the Progeria Research Foundation (PRF) and Boston Children's Hospital were not satisfied with such statistics. In 2012, they launched the world's first clinical trial of a drug that could help rapidly aging children. And, according to EurekAlert! they have succeeded in this.

The study of patients with progeria stretched for 2.5 years. The scientists invited 28 children from 16 different countries to participate, 75% of whom were diagnosed with the disease. The children came to Boston every four months and underwent a complete medical examination.

During the entire time, the subjects were given twice a day a special preparation of a farnesyl transferase inhibitor (FTI), which was originally developed for the treatment of cancer. The research team assessed weight dynamics, arterial stiffness (a parameter for heart attack and stroke risk), and bone stiffness and density (a risk parameter for osteoporosis).

As a result, each child felt much better. Children began to gain weight, there were improvements in the structure of bones, and most importantly, in the cardiovascular system.

According to doctors, the results of this study are very encouraging. In the future, it is planned to continue studying FTI drugs and their effect, which will provide additional information about cardiovascular diseases and the normal aging process.

“The results of this trial are encouraging for our family. We look forward to Meghan's future with excitement and hope. We are grateful to the Progeria Research Foundation and all the doctors for their commitment to helping my daughter and all children with progeria,” says Sandy Nybor, mother of 12-year-old Megan, who participated in clinical trials.

Progeria in culture and life

Trust me, it's never too late, or in my case, never too early to be who you want to be. No time limits - start when you want. You can change or stay the same - there are no rules for this. We can make better or worse choices, I hope you make the best one.

This monologue is taken from David Fincher's The Curious Case of Benjamin Button, which is based on the short story of the same name by F. Scott Fitzgerald.

From birth, the hero of this famous story was an outcast, because. from infancy had the appearance and health of an 80-year-old man: he had wrinkles all over his body and atrophied legs. However, time passes, and Benjamin, on the contrary, does not age, but gets younger. Many different ups and downs happen to a man, and, of course, love happens in his life.

There are no such miracles in real life, and progeria patients never become young. But, despite their illness, such people do not cease to be happy. In particular, Leon Botha, a South African artist, musician and DJ, is known to the world not only for his creative work, but also for the fact that he could live up to 26 years with a terrible disease.

Progeria Leon was diagnosed at the age of 4, but the disease did not break his life. This man loved to enjoy every minute, although he realized that an early death was inevitable. For example, in January 2007, a man organized his first solo art exhibition in Durbanville, the theme of which was hip-hop culture as a way of life. Note that the "young" man had several such shows.

Botha was also involved in DJing and turntablism (a kind of DJing) and performed under the pseudonym DJ Solarize in famous clubs. In addition, he collaborated with the South African band Die Antwoord and starred in their video for the song Enter the Ninja.

But, unfortunately, progeria spares no one. Therefore, on June 5, 2011, Botha died of a pulmonary embolism - a pathological condition when part of a blood clot (embolus), detached from the primary site of its formation (often the legs or arms), moves through the blood vessels and clogs the lumen of the pulmonary artery.

Today, scientists around the world are studying this mysterious disease. From the list of deadly, they want to move it to the list of intractable. It is worth noting that science has already achieved great results in this direction. However, there are many questions that need to be sorted out, namely: what are the similarities and differences between particular cases of progeria and normal aging of the body, how are the genetic causes of the Werner and Getchinson (Hutchinson)-Gilford syndrome related, and how to resist accelerated aging of the body. Perhaps, after some time, there will be answers, and specialists will be able to prevent the development of the disease, thereby they will be able to prolong the life of people with progeria.

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All people age. According to scientists, if it were not for the destructive effects of the external environment and our addiction to pleasures that are harmful to the body, we would live up to 130, or even up to 150 years. And 16 years ago, on August 29, 2001, scientists even announced that they had found a gene for longevity. So, perhaps, in the near future we will be able to live the entire life span allotted to us by nature. But while we grow old and die in the vast majority before 80-90 years. And some diseases reduce this already not so long period at times. And the most "deadly" among them, in the truest sense of the word, is progeria. MedAboutMe found out what it's like to grow old in a decade and a half to two decades.

Aging is a natural process inherent in every living organism on Earth. All available theories on the topic "Why do people age?" can be divided into two large groups. Supporters of one of them argue that aging was conceived by nature for the further evolution of species and society. Others are sure that there are no global ideas here - just damage at the gene and cellular level accumulates over time, which leads to wear and tear of the body.

One way or another, but really in the course of a person's life, the results of internal failures and errors, as well as the consequences of external influences, accumulate in his cells and tissues. Key factors in aging include:

• Exposure to reactive oxygen species (ROS), which, of course, our body needs, but not always and not everywhere.
• DNA mutations in somatic cells (i.e. body cells). The genome is not a structure frozen in time and space. It is a living and subject to change design.
• Accumulation of damaged proteins, which are a by-product of ROS action or failures in metabolic processes.
• Shortening of telomeres - the terminal sections of chromosomes. True, recently scientists have begun to doubt that aging is associated with telomeres, but so far this theory is still popular.

Progeria, which will be discussed in this article, is not aging - in the sense in which science understands it when it talks about life expectancy, wear and tear of the body, etc. This disease looks like aging, although in fact it is severe a genetic disease associated with a violation of the production of certain proteins.

Progeria - diseases of children and adults

The Englishman Jonathan Hutchinson in 1886 first described a 6-year-old child in whom he observed skin atrophy. The name of an unusual disease (from the Greek word "progeros" - aged ahead of time) was given to her in 1897 by Dr. Gilford, who studied and described the nuances of the disease. In 1904, Dr. Werner published a description of adult progeria - using the example of four brothers and sisters who suffered from cataracts and scleroderma at once.

It is believed that F. Scott Fitzgerald wrote his story "The Curious Case of Benjamin Button" in 1922 under the influence of information about patients with progeria. In 2008, Brad Pitt played the protagonist of the book in the film The Curious Case of Benjamin Button.

There are two types of progeria:

• A disease affecting children is Hutchinson-Gilford syndrome.

This is a rare pathology. It occurs in 1 child out of several million. It is believed that in the world today there are no more than a hundred people suffering from childhood progeria. True, scientists suggest that we can talk about about 150 more undiagnosed cases.

• A disease that affects adults is Werner's syndrome.

This is also a rare disease, but not as rare as childhood progeria. People with Werner's syndrome are born in 1 case out of 100 thousand. In Japan - a little more often: 1 case per 20-40 thousand newborns. In total, a little less than 1.5 thousand such patients are known in the world.

Childhood progeria is only indirectly related to true aging. This is a disease from the group of laminopathies - diseases that develop against the background of a problem with the production of lamin A protein. If it is not enough, or the body produces the “wrong” lamin A, then one of a whole list of diseases develops, which includes Hutchinson-Gilford syndrome.

The cause of childhood progeria is a mutation in the LMNA gene, which is located on the 1st chromosome. This gene encodes the compound prelamin A, from which the protein lamin A is obtained, which forms a thin plate - lamina, covering the inner membrane of the nucleus. It is necessary for anchoring all kinds of molecules and internal structures of the nucleus. If there is not enough lamin A, the internal frame of the cell nucleus cannot be built, it cannot maintain stability, which leads to accelerated destruction of cells and the whole organism. In addition, lamin A plays a key role in cell division. It regulates the breakdown and restoration of the cell nucleus. It is not difficult to imagine what can happen if this protein is not enough or it is not what it should be. Mutation of the LMNA gene leads to the formation of the "wrong" protein - progerin. It is he who causes the accelerated "aging" of children.

According to recent data, the mutation occurs in the early stages of embryonic development and is almost never transmitted from parent to child.

A few years ago, scientists discovered that healthy cells also produce progerin, but in significantly lower amounts than in Hutchinson-Gilford syndrome. Moreover, it turned out that with age, progerin in normal cells becomes more. And this is the only thing that really links childhood progeria and the aging process.

Adult progeria is the result of another mutation, in the WRN gene. This gene encodes a protein necessary to maintain chromosomes in a stable state, as well as involved in the processes of cell division. In the presence of a mutation in the WRN gene, the structure of chromosomes is constantly changing. The frequency of spontaneous mutations increases 10 times, while the ability of cells to divide falls 3-5 times compared to healthy cells. Telomere length also decreases. And these processes are already really close to the aging that we have in mind when looking at older people on a bench.

For the first time, the syndrome of premature aging was discussed 100 years ago. And no wonder: such cases occur once in 4-8 million babies. Progeria (from the Greek pro - earlier, gerontos - old man) - or Hudchinson Gilford's syndrome. This disease is also called childhood old age. 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. These children usually die at the age of 13-14 after several heart attacks and strokes against the background of progressive atherosclerosis, cataracts, glaucoma, complete loss of teeth, etc. And 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. 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.

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.

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 has practically no chance to live even to 25, and this is probably the saddest thing.

Adult progeria (Werner's syndrome) is a hereditary or familial disease. It is manifested by premature aging, starting at the age of 20-30 years, accompanied by early graying, baldness and arteriosclerosis. 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.