home Consultations Hunter disease is a rare genetic pathology. Hunter's disease (syndrome)

Hunter disease is a rare genetic pathology. Hunter's disease (syndrome)

In chapter

Court and case

Mucopolysaccharidosis is a scary word. In Russia this is almost a death sentence. Because at least from this rare disease and came up with a medicine, but according to Forbes, it is one of the most expensive in the world. The less common the disease, the medicine is more expensive. The cost of one bottle is more than three thousand dollars. In Russia, they are not developing a drug for mucopolysaccharidosis at all and are forced to purchase it abroad.

The drug “Elapraz” is a drug that patients with mucopolysaccharidosis (otherwise called “Hunter syndrome”) cannot live without; it is an artificial enzyme. Its deficiency or absence in the child’s body leads to the accumulation of toxins in the blood. Gradually, the sick child’s bones become deformed and destroyed. internal organs and nervous system, mental degradation occurs. The earlier the introduction of this enzyme into the body begins, the greater the chance that the child will grow up healthy.

A life-saving medicine for the treatment of children with mucopolysaccharidosis appeared in 2006 in America. It was possible to register it in Russia only two years later. According to well-known Russian custom, officials stubbornly opposed the use of the drug in our country, citing the lack of clinical trials. Meanwhile, due to bureaucratic delays, sick children lost precious time, and the deterioration of their condition had irreversible consequences and even deaths.

In 2009, by order of the Government of the Republic of Bashkortostan, budget money was allocated for medications for five children with Hunter syndrome. But they were only enough for seven months of treatment. “Expensive,” the officials decided and made a conclusion - the drug is dubious, “does not have a positive effect,” does not cure...

Mothers went to court to prove their children's right to receive life necessary medications. The trials continued for two years. All this time the children remained without treatment. All this time, while mothers called on medical officials to show compassion and respect the laws, the children’s condition rapidly deteriorated

Court decisions invariably stated: “The legislation does not provide for the provision of drugs to such patients.” The doctors treating the children were present at the trials, but none of them stated that interrupting treatment is fraught with irreversible and deadly changes in the patients’ health.

The prosecutor's office has investigated this case several times. The mothers went through all the authorities, from the lowest to the highest, and everywhere there was one answer: “Not provided for”... When the mothers finally reached the republican prosecutor's office, the Kirov court made a positive decision.

But time was lost...

A year in the life from the French

When the Hunter Syndrome Charitable Society was created, it was hoped that it would be supported by the government and the Ministry of Health, but this did not happen. The head of the public organization, Eleanor Romanova, herself the mother of a sick child, went through all the trials, hoping that justice would prevail. But in our country, the salvation of the dying is the work of the dying themselves.

On this topic

In Bashkiria, the former head of the life support department of the education department in the administration of Neftekamsk came under investigation on suspicion of abuse of power and official forgery.

As Eleonora Anatolyevna herself says, her family was forced to register at their place of residence in Moscow. To do this, it was necessary to purchase at least half a meter of living space in the capital and visit dozens of offices. But a mother saving a sick child is an irresistible driving and penetrating force that no office can stop. And she achieved her goal - Yaroslav began to receive elapraz as a resident of Moscow, although the capital did not accept strangers, hissed at them and insulted them with their provincial origins.

Having hit the thresholds in Moscow, having heard enough of the traditional “come in large numbers” and “there is not enough medicine for our own here,” the Romanov family left for France. And you don’t need to think that they are super rich. It’s just that not everyone knows that if the disease cannot be treated in Russia, then by collecting the appropriate documents, you can receive medical care completely free of charge in another country. And the rent for an apartment, whether in Moscow or Nice, is a thousand dollars...

This is where Eleonora Anatolyevna and Yaroslav felt the difference between domestic and foreign medicine! Due to the child’s illness, their visa was immediately extended for a year. Since the supply of medicine was only for a month, our son was provided with elaprase free of charge, and even social benefits several hundred euros monthly.

In France there was no need to beg for help. Everything was offered special services. And medicines, and financial resources, and examination. In addition, the child underwent a course of rehabilitation therapy. And Eleonora Anatolyevna, at the invitation of the International Center for Mucopolysaccharidosis, attended a congress on this disease, where she saw entire delegations of adults with Hunter syndrome from different countries. It is in Russia that such patients rarely live to be twenty years old, but in the world people with Hunter syndrome live practically full life. They study, work, create families. A timely diagnosed disease and appropriate treatment do not lead the patient to severe disability. People walk, hear, talk and do not lose the ability to think.

Legalized

On November 21, 2011, the long-awaited Federal Law No. 323-FZ “On the fundamentals of protecting the health of citizens in Russian Federation”, which, it would seem, finally established the concept of “rare (orphan) disease”, as well as the procedure for providing citizens with such ailments with vital medicines. This responsibility is assigned to the authorities state power subjects of the Russian Federation. This means that now everything depends on the Ministry of Health of the republic.

Currently, three children in Bashkortostan are receiving elapraz. Only three out of five patients with this terrible disease. One girl, whose treatment has already been recognized as futile, is fading away in orphanage, the mother of a teenager from Uchaly refused the drug, because, as doctors say, rather than interrupting treatment later, it is better not to start it. This woman has no confidence in our medical charity. She had already been cruelly deceived in it once.

It took the state six months to launch the heavy mechanism of law enforcement. These children need elapraz constantly, regularly and on time. Ruslan Romanov stopped walking during the six-month break in treatment. But during the time he was taking the drug, he even learned to climb stairs.

There is a law, medicines are registered, there are even court decisions. But the mothers are worried. They, who have gone through the courts and achieved, at the cost of their children’s health, the adoption of a law requiring regions to treat them free of charge, are justifiably afraid that the republican authorities will change their minds about investing money in expensive patients. After all, the high cost of this remedy makes it practically unattainable for most parents with a child with Hunter syndrome. There is only hope left for the state.

In Russia today there are 250 children suffering from mucopolysaccharidosis. Treatment of one child costs more than a million rubles a month, because the medicine that delays the development of the disease is produced by a single company, albeit in sufficient quantities. But in Russia no federal program for the treatment of such patients, the regions do not have enough money, according to officials, to purchase it in sufficient quantities.

However, there is one strange thing here. Treatment of a child in the USA, when converted to rubles, costs 12 million a year, and in Russia it is already about 30 million. Is transportation really that expensive? Russian healthcare is far from the richest, but it seems that someone is trying to profit from the terrible grief of these families, forcing the state to spend huge sums on medicine, the price of which is obviously almost two and a half times lower.

When purchasing a drug, a public tender provides for the condition that the price for the product is initially set regional ministry healthcare. This means that the purchase price cannot exceed that declared by the Ministry of Health of the republic. It, in turn, logically, should be determined based on the number of patients who need the drug and the amount included in the republic’s budget for the purchase of the drug.

This means that either the cost of the medicine declared in the tender is, for some reason, inflated by the ministry, or after purchase it is sold at a markup of two and a half times.

Eleonora Anatolyevna contacted the pharmaceutical company Shire Pharmaceuticals, which supplies Elaprase, with a question: why is the drug sold in Russia at such an unaffordable price? And I received the answer: “We understand the suffering that accompanies the process of caring for a patient with Hunter syndrome, but we cannot be responsible for the prices that are set by Russian authorities.”

But in addition to expensive medicine, such children need special food, wheelchairs, not to mention special exercise equipment and wall bars. Not everyone can afford even simple diapers in sufficient quantity.

Funds can't afford it

Many parents of sick children turn to charities. In some they answer honestly and immediately - we won’t take it. In the rest they ask for more and more documents, promise to consider them, they say that we have to wait, that there are many petitioners and applicants. Then a month passes and the certificates become outdated. Somewhere they ask for a certificate to “refresh”, somewhere they continue to assure that the procedure is proceeding as usual and the moment for making a decision will soon come, but every time this moment somehow does not come, but people believe and wait...

Few people manage to receive anything from charitable foundations. After all, it is much easier and more profitable for them to hold a large-scale charity event - under fanfare, camera flashes and spotlights, solemnly and loudly. So Eleanor Romanova turned to charitable foundations for help many times. And every time the same answer is given - they say, we have been participating for many years and repeatedly, financing, providing and implementing, opening branches, spending billions of rubles... But the fund’s budget for the current year does not plan to help you. We will try to plan for the future, but don't get your hopes up too much...

Dialogue needed

The diagnosis of a rare disease is very difficult. Usually, genetic analysis is done by the attending physician last. Groups of patients of each type of “rare” disease are extremely small. Hunter syndrome is very rare - it accounts for 1-2% of all diseases in the world. Physician alertness required general practice, pediatrician, need genetic advice, timely and accessible laboratory diagnostics rare diseases. Everything is important - the presence of specialized medical centers, accessible by location and free for patients, equipped with modern medical equipment and having on staff highly professional doctors, nurses, psychologists who have information and practical skills in providing first aid, treating and monitoring “rare” patients...

All this will be achievable only when the problems and needs of patients become known not only to their loved ones and their attending physicians. The time has come to establish a dialogue between families with children with rare genetic diseases, the Ministry of Health and the Government of the Republic of Belarus. Public organizations, uniting these people, see a solution in the creation of a public Council to protect the rights of children suffering from rare genetic diseases.

Unfortunately, representatives of the Ministry of Health do not take part in press conferences and round tables held by the Hunter Syndrome charitable society, but any dialogue implies two-way communication... Whether parents will receive help and understanding from the state, time will tell.

Hunter syndrome is a rare inherited disorder that results from the absence or dysfunction of a lysosomal enzyme (protein) due to mutations in the gene IDS. The enzyme is iduronate-2-sulfatase. It is a debilitating condition with variable rates of progression.

The function of uronate-2-sulfatase is to destroy long chains of glycosaminoglycans (formerly known as mucopolysaccharides). A defective enzyme causes glycosaminoglycans to accumulate, which damages several organs.

Hunter syndrome belongs to a group of diseases called mucopolysaccharidoses, also known as mucopolysaccharidosis II or MPS II.

Predominant in men with a frequency of 1 in 100,000-1 in 170,000 people.

Depending on the age of onset, it is either mild or severe. Soft form(option IDS- gene: c.1122C>T) develops in children aged 4 years and older. A severe form (lack of a functional enzyme) develops in children aged 2.5 years and older.

Causes

Hunter syndrome is an inherited, rare, X-linked recessive lysosomal condition. The infected chromosome is passed on from the mother, who has no symptoms due to the presence of a normal chromosome in the pair. Boys are more likely to inherit the disease. This explains the predominance of the condition in men.

Signs and symptoms

Although babies with Hunter syndrome appear normal at birth, characteristic symptoms begin to appear between the ages of 2 and 4 years. They vary depending on the age of onset and severity of the condition. Symptoms appear as a continuum between severe and weakened variants of the disease.

The nose becomes wide;
The tongue is enlarged;
The cheeks become enlarged and rounded;
Lips thicken;
The voice becomes hoarse due to increased vocal cords;
The liver and spleen become enlarged (hepatosplenomegaly);
Fluid accumulates in the brain (hydrocephalus);
A hernia (soft enlargement or prolapse) develops in the lower abdomen (groin) or around the belly button (umbilical);
Enlarged head (macrocephaly);
Hearing loss;
Thick, inelastic skin;
Frequent ear infections;
Characteristic skin growths that look like pebbles;
Heart valve problems;
Aggression in behavior;
Joint stiffness;
Delayed speech, walking;
Growth is limited;
Carpal tunnel syndrome;
Problems with the retina leading to poor vision;
Compressed, damaged spinal cord.

To learn more Diagnostic criteria Holt Oram syndrome

IN severe cases intellectual, mental abilities are compromised (cognitive impairment) along with developmental delay (developmental regression), which is not observed in mild cases.

Diagnostics

Diagnosis of Hunter syndrome includes identifying clinical symptoms, molecular features, biochemical characteristics of the condition.

Clinical diagnosis

Full family and medical history patient. Some characteristic symptoms observed in infants under 6 months are enlarged spleen, liver, persistent ear infections, hernia. Other symptoms include problems with joints and skeletal bones, breathing problems, and facial distortions. Preliminary surgical history the child should be taken as it is often found in children who have undergone surgery.

Gene testing

Detection of mutations in a gene IDS useful but not required for diagnosis. Families should undergo genetic counseling if mutations are detected. Gene testing helps identify female carriers in a family. Prenatal enzyme gene testing IDS useful for diagnosing affected fruits. Testing for the mutation has been noted to significantly help identify female carriers as well as the affected fetus.

Biochemical tests

Enzyme analysis. Enzyme activity detection is useful in understanding IDS enzyme deficiency. This effective tool to diagnose Hunter syndrome, although it cannot detect gene mutation carriers IDS.
GAG urine test: measures general levels glycosaminoglycans (GAGs) or long-chain sugars in urine. However, it is not very sensitive to many false negatives.

Laboratory tests are very effective in confirming the diagnosis of Hunter syndrome because there are many symptoms that are common to different states group of mucopolysaccharidoses.

Other diagnostic tests for some symptoms:

These tests should be performed annually as a surveillance strategy to monitor patients.

Treatment

Once diagnosed, patients contact a clinical geneticist to begin immediate treatment. Treatment of Hunter syndrome requires multidisciplinary collaboration. Family doctor or the pediatrician helps the family and patient coordinate meetings with multiple specialists (ophthalmologist, anesthesiologist, neurosurgeon, podiatrist, speech therapist, physical therapist, dentist, behavioral therapist).

Exist various methods treatments related to individual problems:

Replacement heart valve;
Reduction inguinal hernia;
Shunting fluid accumulation in the brain;
Tonsillectomy;
Removal of adenoids.

To learn more How to get rid of white coat syndrome

Enzyme replacement therapy (ERT)

In 2006, a manufactured (recombinant) form of iduronate-2-sulfatase, idursulfase (Elaprase T), was approved to treat people with mild Hunter syndrome and is now approved in more than 40 countries. With the exception of cognitive impairment, ERT improves other symptoms if patients are treated early. However, when ERT is treated after a delayed onset of symptoms, it is not as effective. Side effects– fever, rash, headaches.

Hematopoietic stem cell transplantation (HSCT)

This particular form of treatment has shown benefits. However, the benefits of HSCT in MPS II have not yet been confirmed. The idea of transplantation bone marrow or umbilical cord blood) is to replace sufficient enzyme activity to slow or stop the progression of the disease.

Prenatal testing provides families with an opportunity to explore available options treatment of this condition. It is a genetic condition, controlled only by enzymes replacement therapy, but cannot be cured.

Mucopolysaccharidoses unite the group hereditary diseases, which are based on a violation of the metabolism of mucopolysaccharides that provide normal functioning connective tissue. IN medical literature About 14 types of this pathology have been described.

Mucopolysaccharidosis type 2 is called Hunter syndrome. This is an X-linked disease with a recessive mode of inheritance. As a rule, Hunter syndrome is detected in boys. In isolated cases, cases of the disease in girls are possible due to inactivation of a healthy X chromosome.

Causes

Children suffering from this disease have hydrocephalus

The direct cause of this pathology is considered to be a mutation in the structural gene of the lysosomal enzyme (iduronate-2-sulfatase), which is involved in the synthesis of mucopolysaccharides. Modern medicine About 300 types of mutations of this gene are known, most of them are unique. These can be small or large deletions, gene rearrangements, etc. Such mutations lead to changes in the structure or disruption of the functional ability of the enzyme and the accumulation of certain classes of mucopolysaccharides in lysosomes. And this happens everywhere:

Features of the flow

The clinical manifestations of mucopolysaccharidosis type 2 are varied. At the same time, the severity pathological symptoms may vary. IN clinical practice Conventionally, two forms of the disease are distinguished - mild and severe, although there are many more phenotypes.

The severe form of the syndrome debuts at the age of 1-3 years. Its course resembles mucopolysaccharidosis type 1, but the disease progresses more slowly and its symptoms are less pronounced. In such patients the following is detected:

structural change facial section skulls and torsos according to the type of gargoilism;
growth retardation;
multiple bone dysostosis;
joint stiffness;
mental retardation;
roughening of the skin and its thickening;
excess hair growth;
the presence of smooth, hairless areas of skin resembling sea pebbles in the interscapular region, on the lateral surfaces of the chest, and neck;
signs of hydrocephalus;
hearing loss;
chronic;
cardiac pathology, etc.

It should be noted that with mucopolysaccharidosis type 2, corneal opacification does not occur.

The term "Gargoilism" characterizes appearance patients with mucopolysaccharidosis. It comes from the name of the figures depicted at Notre Dame Cathedral in France. Its typical manifestations are:

rough facial features;
drooping forehead;
thick lips and tongue;
sunken bridge of the nose;
wide nose with large nostrils;
ocular hypertelorism (widely spaced eyes);
low-set ears;
rare teeth;
small height;
disproportionate skeletal structure (short torso and neck);
bone deformities (skull, sternum, spine);
big belly, etc.

A mild form of Hunter syndrome manifests itself somewhat later - at the age of 3-8 years, and sometimes 10-15 years. Such children have normal intelligence. The main signs of the disease are:

obstruction upper sections respiratory tract;
heart defects;
limited mobility in joints;
hearing impairment.

If, in a severe form of mucopolysaccharidosis, death occurs in the second decade of life as a result of neurological complications, then with it mild form Life expectancy varies widely and depends on the severity of damage to internal organs. Most common reason the death of such patients is circulatory failure.

Principles of diagnosis and treatment

The diagnosis is confirmed by a biochemical analysis of urine - determination of the level of glycosaminoglycans in it

A doctor can suspect Hunter syndrome by studying in detail the patient’s complaints, the history of his illness and assessing his appearance.

Confirms the diagnosis biochemical research with determination of the level of glycosaminoglycans excreted in the urine. If this level is high, then the next step is to evaluate the activity of iduronate-2-sulfatase contained in leukocytes or skin fibroblasts.

IN difficult cases DNA analysis may be performed. However, this procedure is too complicated and time-consuming, so it is rarely used.

In families with a high risk of developing this pathology, it is recommended to carry out prenatal diagnosis with determination of the activity of the lysosomal enzyme in the amniotic fluid or chorionic villi at early stages fetal development.

Differential diagnosis of Hunter syndrome is carried out with other lysosomal storage diseases.

The management of patients depends on the severity of the syndrome and damage to internal organs. In most cases, treatment is symptomatic. At severe forms illness, such patients may be prescribed idursulfase. The use of this drug is limited due to high cost and the need for frequent administration (weekly).

Which doctor should I contact?

Children with Hunter syndrome are monitored in large specialized medical centers; They are treated at their place of residence under the supervision of a pediatrician. Additionally, consultations with a cardiologist, neurologist, gastroenterologist, hearing care specialist, speech therapist, and physical therapy specialist are prescribed.

Conclusion

Hunter syndrome – serious disease, which reduces the quality of life of patients and is often the cause fatal outcome. Average duration The lifespan of such patients is about 30 years. Effective and available methods There is currently no treatment for this disease. That's why Special attention focuses on issues of prevention and prenatal diagnosis.

Hunter Syndrome Video Guide:

Description:

Hunter's disease (Hunter syndrome) is one of the forms of mucopolysaccharidosis type 2 (MPS II), a rare recessive X-linked genetic disease.

Causes of Hunter syndrome:

Hunter syndrome occurs as a result of a deficiency of a number of enzymes, which leads to the accumulation of protein-carbohydrate complexes and fats in cells.

Symptoms of Hunter syndrome:

The disease manifests itself in early age(2-4 years) thickening of the nostrils, lips, tongue, stiffness of joints, growth retardation. Up to two years of age, signs such as noisy breathing (obstruction of the upper respiratory tract), repeated rhinitis, inguinal and umbilical hernias.

For timely diagnosis necessary clinical examination with determination of the activity of the enzyme iduronate-2-sulfatase (I2S, sulfo-iduronate sulfatase). The most commonly used laboratory urine screening test is GAG. External signs The disease is the appearance of coarse facial features (gargoilism), a low, rough voice appears, and frequent acute respiratory infections occur. viral infections. Common signs of the disease are thickened skin, short neck, rare teeth.

Treatment for Hunter syndrome:

The genetic nature of the disease causes enormous difficulties in therapy. Currently, there is only one drug available worldwide that actually improves the condition of patients with Hunter syndrome. This is Elaprase, a drug developed pharmaceutical company Shire Human Genetic Therapies Inc., Cambridge, MA. The drug is a recombinant human enzyme iduronate-2-sulfatase.

Palliative treatment.
Currently, due to the lack real methods To influence the cause of the disease, symptomatic therapy is used.

Mucopolysaccharidosis type II(Hunter syndrome) is associated with a deficiency of the enzyme alpha-L-iduronosulfate sulfatase, resulting in the accumulation of glycosaminoglycan dermatan sulfate and heparan sulfate in the connective tissue. Hunter syndrome is less common than mucopolysaccharidosis I, accounting for approximately 14-15% of all forms of mucopolysaccharidosis.

The mode of inheritance of Hunter disease is recessive, linked to the X chromosome. Hunter's disease usually affects only boys, but to date, 7 cases of the disease in girls have been described.

MPS type II occurs with a population frequency of 1:140,000 – 1:156,000.

The inheritance of Hunter syndrome differs from all other MPS diseases, since the gene responsible for it is recessive and linked to the X chromosome (it is called sex-linked), like hemophilia. Girls can be carriers of the disease, but with the exception of rare cases, only boys suffer from this type of MPS.

If a woman is a carrier of MPS II, then there is a 50% risk that the son she gives birth to will suffer from this disease. In addition, there is a 50% risk that her daughter will be a carrier of the disease. It is important to note that not all women who give birth to a child with MPS II are carriers of the abnormal gene. If only one person in a family has MPS II, it cannot be determined whether the mother is a carrier. However, if there are other children in the family with Hunter syndrome, then it is assumed that the mother is the carrier of the disease. Sisters and aunts of a patient with Hunter syndrome on the maternal side can also be carriers and have a 50% chance of passing on the abnormal gene to their sons.

Hunter syndrome is named after professor of medicine Charles Hunter (Manitoba, Canada), who first described cases of this type of disorder in two brothers in 1917.

Coding according to ICD-10 - E 76.1

MANIFESTATIONS OF MPS II

Characteristic changes in facial features are of the “gargoilism” type, which become obvious by the end of the first or second year of life: macrocephaly, protruding frontal tubercles, sunken bridge of the nose, short nasal passages with nostrils turned outward, half-open mouth, large tongue, plump lips. Patients have growth retardation, a short neck, joint contractures, hernias, delayed teething, and short stature hair on the forehead, long thick eyelashes and eyebrows. With age, hair becomes coarser, straighter and lighter (straw-colored).

People with severe Hunter syndrome experience progressive delay mental development and serious progressive physical impairment. People with mild Hunter syndrome have normal level intellectual development, mild and slowly progressive physical impairments, their life expectancy is significantly higher than that of people with a severe form of MPS II.

Most diagnosed patients with Hunter syndrome have normal or near normal intellectual development and noticeable physical abnormalities, which corresponds to medium degree severity of the disease.

To date no reliable way, which allows one to predict the severity of the disease based on the results biochemical tests, since in all forms of Hunter syndrome, patients lack the same enzyme. The form of the disease is determined based on the existing symptoms and abnormalities. Detailed studies have shown that in people with a mild form of Hunter syndrome, the enzyme is still present in the body, although in small quantities, which explains light form course of the disease.

Height

Patients with Hunter syndrome tend to have lower healthy people, but deviations from normal growth vary depending on the severity of the disease. Babies with severe MPS II are often born quite large and grow faster than normal during the first two years. Their growth slows down towards the end of the 2nd year, and thereafter they grow more slowly and reach 120 - 140 cm. People with a mild form of Hunter syndrome usually have normal height.

Skin

This form of mucopolysaccharidosis is characterized by nodular-papular skin lesions, mainly in the area of the shoulder blades, outer and lateral surfaces of the shoulders and hips. These changes are caused by the deposition of lipids and glycosaminoglycans in the dermis.

Skeletal system

There is a “clawed paw” deformation of the hand. Characterized by kyphosis, deforming osteoarthritis hip joints, multiple dysostosis, enlargement of the sella turcica.

Vertebrae in in good condition aligned along a line from the neck to the buttocks. In people with severe Hunter syndrome, the spine is abnormally formed, with one or two vertebrae in the middle of the spine sometimes smaller than the others and slightly misaligned. This displacement of the vertebrae can cause the development of spinal curvature (kyphosis or hump). Typically, with Hunter syndrome, the spine is slightly curved and does not require special treatment.

Joint stiffness is typical in all types of mucopolysaccharidosis, and range of motion may be limited in all joints. Over the years, stiffness can lead to joint pain, which can be relieved with heat and painkillers such as ibuprofen, but these should only be taken under the supervision of a doctor as these medications can cause stomach irritation and ulcers.

Many people with Hunter syndrome stand and walk with bent legs due to stiffness in the hip and knee joints. This, combined with a tight Achilles tendon, sometimes causes them to walk on tiptoes. Sometimes an X-shaped curvature of the legs occurs, which usually does not require treatment. In case of severe deformities, large surgery is required. tibia(for Hunter syndrome, such surgery is extremely rarely required). The feet are wide and inflexible with the toes curled and bent, like those on the hands.

Respiratory system

Characterized by frequent respiratory diseases; repeated otitis media, often leading to progressive hearing loss; obstructive airway diseases.

Typically, people with Hunter syndrome have a flattened bridge of the nose. As a result of bone changes in the midface and thickening of the mucous membrane, the nasal passage is narrower than usual. This structure of the nasopharynx, combined with the accumulation of substances in soft tissues nose and throat can cause the nasal passages to become easily blocked. One of distinctive features children with Hunter syndrome are mucous nasal discharge (rhinorrhea) and chronic infectious diseases ears and sinuses.

The tonsils and adenoids are often enlarged and may partially block the airways. The neck is usually short, which contributes to breathing problems. The trachea often narrows due to a buildup of material and becomes more flexible and soft than normal due to changes in the structure of the cartilage rings in the trachea.

The shape of the chest is irregular and the connection between the ribs and the sternum is not as flexible as normal. That's why rib cage cannot move freely, which, in turn, does not allow the lungs to take in a large volume of air. The diaphragm is pushed upward because the internal organs (liver and spleen) are enlarged, which also reduces the space available to the lungs. If fluid gets into the lungs, there is a high risk of infection (pneumonia). With narrowing of the airways and increased secretion, the risk of asthmatic attacks is high. Many patients during viral disease The use of anti-asthmatic drugs helps reduce coughing and ease breathing.

Many patients with Hunter syndrome have noisy breathing even when there is no infection. Their sleep is restless and often accompanied by snoring. Sometimes the patient stops breathing for short periods during sleep (apnea). Noisy breathing that stops and starts again can sometimes be very frightening for parents, but such stops in breathing for 10-15 seconds are considered by doctors as the norm. It is important to know that many patients with MPS II can breathe this way for many years.

When breathing stops, the oxygen level in the child's blood decreases, which can cause heart problems. If a child experiences significant choking or interruption of breathing, it is necessary to consult a specialist who can evaluate the child's condition during sleep using special tests.

Sometimes apnea is treated by removing the tonsils and adenoids, performing airway ventilation using continuous or bilevel positive pressure, or performing a tracheostomy (an operation to cut the anterior wall of the trachea and then insert a cannula into its lumen or create a permanent opening - a tracheostomy). Many experts believe that tracheostomy is indicated for patients with MPS II. early stages development of the disease than is usually carried out. Patients after tracheostomy feel much better, as breathing improves during sleep.

Organs of vision

Retinal pigmentary degeneration. Hunter disease is less characterized by corneal opacity, in contrast to MPS types I and VI. In patients with severe form of MPS II, retinal dystrophy is often detected, leading to impaired peripheral vision and decreased twilight vision. Possible disc swelling optic nerve caused by increased intracranial pressure. Glaucoma is rare.

central nervous system

Psychomotor delay and speech development expressed from 1.5-3 years. In severe cases of the disease, severe mental retardation develops by the age of 8 years. Many researchers associate the developmental delay of people with a severe form of Hunter syndrome with the accumulation of mucopolysaccharides in the neurons of the brain. In mild forms of Hunter syndrome, delays in intellectual development not visible. Brain functions are affected by processes typical of Hunter syndrome, such as: reduced level oxygen (hypoxia), loss of sleep due to apnea, high blood pressure fluid in and around the brain (intracranial pressure, hydrocephalus), decreased vision and hearing. Signs of hydrocephalus often appear slowly and imperceptibly, and may include changes in behavior, headaches, and blurred vision.

The presence of convulsions is characteristic (especially in severe forms). Symptomatic epilepsy develops, as a rule, with severe or moderate course of the disease. In patients with mild and clinical signs it is extremely rare.

Carpal tunnel syndrome is a common compression neuropathy in patients aged 3 to 10 years. In the initial stage of the disease, numbness of the affected hand, difficulty performing fine movements, and decreased sensitivity of the fingers occur. These symptoms are rarely noted by the child and are not regarded by parents as pathological. Later, a tingling sensation appears in the fingertips of the hand and over time the process can spread to the forearm and shoulder. Patients rarely report pain until loss of function occurs. pain is rarely reported until loss of function occurs.

Swallowing disorders: bone changes lead to decreased mobility lower jaw, which limits the ability to open the mouth and chew.

Behavioral disorders - hyperactivity, disinhibition, aggressiveness and stubbornness, as a rule, occur in children with moderate and severe forms of mucopolysaccharidosis. Behavior problems have a significant impact on daily life child and his social adaptation. As the cognitive deficit increases, autistic traits join hyperactivity and aggressiveness, and a gradual loss of speech skills is noted.

The cardiovascular system

Heart damage is observed in most patients. As with mucopolysaccharidosis type I, damage to the valves, endomyocardium, coronary arteries. Pathology of the mitral valve is most often observed, and there may be both insufficiency and stenosis of the left atrioventricular orifice. However, valve damage is much less pronounced in children and adolescents and, as a rule, manifests itself in adult patients. The heart valves can be damaged by accumulated mucopolysaccharides, causing heart murmurs (sounds caused by fast, erratic flows of blood into the heart). Normally, the heart valves work in such a way that when blood passes from one chamber of the heart to another, blood is not allowed to flow in the wrong (reverse) direction. If the valve is loose, it does not close tightly and a small amount of blood may flow backwards. This results in rapid, intermittent countercurrents in the overall flow, which in turn generates noise. Most patients with Hunter syndrome have some degree of this leakage—a heart defect. Often, MPS patients have problems with the aortic or mitral valve which may progress slowly over many years without visible signs clinical manifestations. If the patient's condition worsens, it may be necessary surgery to replace damaged valves.

In severe cases of Hunter syndrome, the heart muscle itself can be damaged due to accumulations of mucopolysaccharides (cardiomyopathy). The heart may also be overworked due to having to pump blood through the altered lungs (abnormally enlarged right side heart disease as a result of pulmonary disease or right-sided heart failure).

Due to unusual specific problems, which may occur with mucopolysaccharidosis, it is highly advisable to obtain advice from a cardiologist who has experience working with MPS patients.

Gastrointestinal system

Possible diarrhea associated with accumulation of GAGs in nerve cells digestive tract. Constipation often develops with age. From an early age, hepatosplenomegaly is noted. Umbilical and inguinal hernias are characteristic.