Families with several children with gurler syndrome. Mucopolysaccharidosis type I in children

Syndromes Gurler, Gurler-Sheye and Sheye is one disease known as mucopolysaccharidosis I (MPS I), also referred to as MPS I H, MPS I H/S, and MPS I S, respectively. Gurler syndrome is one of the most severe forms and is named after Gertrude Gurler, who described a boy and a girl with the condition in 1919. In 1962, Dr. Scheie, an ophthalmologist, observed a patient with corneal clouding and a very mild form of the syndrome. The disease he described was called Scheye's syndrome. Scheye syndrome was thought to be a different form of mucopolysaccharidosis (MPS) and distinct from Hurler syndrome. The biochemical changes in MPS I were elucidated in 1971, and it was found that Schie's syndrome and Hurler's syndrome have the same cause - a decrease in the activity of the alpha-L-iduronidase enzyme. Later, several cases with intermediate forms of the disease were described. They were neither severe nor mild and were classified as Hurler-Scheie syndrome. It has now become known that MPS I is very diverse in its clinical manifestations, despite the fact that they have mutations in the same gene.

Hurler syndrome (mucompolysaccharidosis I H - Hurler), occurs with a population frequency of 1:40,000 - 1:100,000

Scheie syndrome (mucopolysaccharidosis I S - Scheie), occurs with a population frequency of 1:40,000 - 1:100,000

Hurler-Scheie syndrome (mucopolysaccharidosis I H / S - Hurler-Scheie), occurs with a population frequency of 1: 100,000

ICD-10 coding— E76.0

MANIFESTATIONS OF MPS I

Growth

With MPS I, there is usually a significant growth retardation. Babies with Hurler syndrome are often born quite large and grow faster than normal during the first year. Their growth slows down towards the end of the 1st year and usually stops at the age of 3 years. They grow up to 120 cm. Height with Hurler-Scheye syndrome is usually no higher than 152 cm. Patients with Scheye syndrome usually have normal height.

Intelligence

In Hurler syndrome, GAGs accumulate in the cells of the nervous system, which causes a slowdown in their development at the age of 1-3 years and a progressive loss of acquired skills in the future. Depending on the severity of the disease, the degree of neurological and intellectual impairment varies: some children can only speak a few words, while others can speak well and read a little. They love nursery rhymes, songs and simple riddles. It is important to help children learn as many skills and knowledge as possible before the disease progresses. Even when children begin to lose acquired skills, they still continue to understand and enjoy life.

Patients with Hurler syndrome have numerous problems with health that greatly hinder their learning - chronic otitis media, decreased vision, hearing loss, joint stiffness, hydrocephalus and respiratory disorders. Appropriate treatment of these problems can greatly help in the education of these children.

In Hurler-Scheie syndrome, the level of intellectual development is normal, but some have slight learning difficulties. In addition, other health problems can interfere with learning and communication. Patients with Scheye syndrome have normal level intellectual development, but there is evidence of the presence of psychological disorders. One of Dr. Scheye's patients had a very high level of intelligence.

Appearance

In the first year of life, the shape of the skull changes dramatically in a child. The skull of babies is soft, and the individual bones of the skull are separated by thin fibrous tissues called sutures. In front of the forehead and behind near the top of the head are the anterior and posterior fontanelles, soft places in the skull, which close during the first years. In Hurler syndrome, the suture along the top of the head fuses earlier than it should, and so the skull pulls back and forth, becomes elongated, and the frontal tubercles begin to protrude. Often a protrusion is seen on the forehead where the skull has closed prematurely.

Among other external features, a wide nose with a flat nose bridge and wide nostrils is also noted. The eye sockets are shallow, so the eyes protrude slightly forward. The tongue is enlarged and may protrude from the mouth. Very often, children are misdiagnosed with hypothyroidism precisely because of the altered appearance. Hair in patients with MPS is usually very coarse and thick, sometimes there is increased hair growth on the back and arms.

The appearance of people with Scheye syndrome is very different. Adults are usually stocky, and their body is shorter than the limbs, the neck is somewhat shortened. Patients with Scheye syndrome have practically no external features.

Skeletal system

On the part of the osteoarticular system in MPS I, multiple symptoms are detected. All patients develop stiffness of all groups of joints, as a result of contractures of the interphalangeal joints and shortening of the phalanges, deformities of the hands are formed according to the "clawed paw" type. The hip joints are formed incorrectly, the femoral heads are small, flattened. Some babies with MPS I have hip subluxation. This problem should be corrected immediately after birth, as it is difficult to deal with later.

Many patients with MPS I have an impaired gait, standing and walking with flexed knees and hips. Sometimes an X-shaped curvature of the legs can be observed, which usually does not require treatment. The feet are wide and inflexible, the toes are tucked in and twisted. Iliac bones acquire a "triangular" deformation.

X-ray changes seen in Hurler syndrome are described as multiple dysostosis. The clavicles are shortened, thickened. The ribs are described as "oar-like". The phalanges of the hands and feet are shortened and have a trapezoidal shape. Kyphosis, kyphoscoliosis are formed. The bones of the spine are normally aligned in a line from the neck to the buttocks. In Hurler and Hurler-Scheie syndrome, the spine may be poorly formed, its vertebrae cannot interact stably with each other. One or two vertebrae in the middle of the back are sometimes smaller than the rest and slightly shifted. Such a displacement of the vertebrae can be the cause of the development of curvature of the spine (kyphosis or humpback). However, usually with the disease, the curvature of the spine is quite mild and does not need treatment.

The bones that stabilize the connections between the head and neck are poorly formed in MPS, making the neck unstable. In some cases, surgery is indicated to connect all the bones to each other. If severe pain or weakness or leg trembling occurs, a neck examination (MRI and X-ray in flexed and extended positions) should be performed to assess the condition of the cervical vertebrae and spinal cord.

central nervous system

progressive mental disorders are characteristic of the Hurler syndrome, while in mild forms of MPS I (Gurler-Scheie and Scheie syndromes), the intellect of patients practically does not suffer or mild cognitive impairment is observed. Psychomotor development in Hurler syndrome goes with a noticeable age lag and reaches its maximum development at the level of 2-4 years, then stops and passes (along with motor development) into the stage of regression, reaching complete dementia. However, systematic studies aimed at the development of cognitive functions contribute to a longer preservation of intelligence.

Behavioral disorders: Cognitive regression along with severe hearing loss, lack of sleep have a significant impact on the child's behavior. As cognitive deficits increase, autistic traits join hyperactivity and aggressiveness.

Medical therapy, aimed at controlling destructive behavior, is often ineffective. Progressive communicating hydrocephalus is the most common symptom Hurler syndrome and rarely occurs in mild forms of MPS type I (Gurler-Scheye and Scheye syndromes).

With compression of the spinal cord caused by thickening of its membranes, note: gait disturbance, muscle weakness, clumsiness with intact motor skills and dysfunction Bladder. Seizures are common in severe disease and should be assessed. neurological status. In patients with mild clinical signs, seizures are much less common. Disease progression usually responds well to anticonvulsant monotherapy.

Carpal tunnel syndrome is a common compression neuropathy in patients aged 5 to 10 years and adults. People with MPS I sometimes experience pain and loss of sensation in their fingertips caused by carpal tunnel syndrome. The wrist is made up of eight small bones that are connected by fibrous ligaments called ligaments. The nerves run through the wrist between the carpal bones and ligaments. Thickening of the ligaments puts pressure on the nerves. This nerve injury causes dystrophy of the muscles at the base of the thumb. In this case, the patient has difficulty grasping objects.

If a child complains of pain and numbness of the fingers, especially at night, a study called a nerve conduction study should be done. Such a study can show whether carpal tunnel is the cause of these symptoms. If the child has any weakness of the hand or the muscle mass at the base of the thumb decreases, an examination by a neurologist is necessary.

Left untreated, it can lead to irreversible contracture of the distal interphalangeal joints, as well as impairment or loss of sensation in the first three fingers and paresis of the thenar muscles. Unfortunately, patients rarely report pain until loss of function occurs.

Brain and spinal cord
Neurological and intellectual disorders in Hurler syndrome are associated with the accumulation of GAGs in brain neurons. With Scheye and Gurler-Scheie syndromes, this does not happen. But we should not forget that other disorders can secondarily affect brain function - reduced level oxygen, sleep disturbances due to sleep apnea, increased fluid pressure in and around the brain (cerebral hydrocephalus), hearing and vision problems.

The brain and spinal cord are protected from shock by the cerebrospinal fluid that circulates around them. In people with MPS I, the circulation of cerebrospinal fluid may be blocked. This blockade (open hydrocephalus) causes an increase in intracranial pressure which can lead to headaches and developmental delay. If hydrocephalus is suspected, a CT scan or MRI should be performed. If the diagnosis is confirmed, hydrocephalus is treated by inserting a thin tube (shunt) that pumps fluid from the head into the abdominal cavity. The shunt has a pressure-sensitive valve that allows cerebrospinal fluid to be pumped out when the pressure around the brain gets too high.

organs of vision

The visual disturbances described here are common to all forms of MPS I. The cornea may become cloudy due to accumulation of GAGs, which destroys the layers of the cornea. If the clouding of the cornea is severe, vision may be impaired, especially in dim light. Some patients cannot stand bright light because the cloudiness causes the light to refract incorrectly. In this case, wearing a cap with a visor and sunglasses can help. Many patients with MPS I undergo corneal transplantation, resulting in improved vision.

The deposition of mucopolysaccharides in the retina can lead to loss of peripheral vision and nyctalopia, or night blindness. The child may not want to walk in the dark or wake up at night and be frightened. It is advisable to leave a night light on in the bedroom and hallway. Sometimes vision problems can occur due to changes in the retina or glaucoma, that is, increased eye pressure which should be checked during regular check-ups with an ophthalmologist. It is often difficult to determine which problems are the main cause of visual impairment. With the help of special studies, the ophthalmologist will help to determine what is causing the deterioration of vision - due to the passage of light (cornea) or due to the reaction of the eye to light (retina or optic nerve disease).

Hearing

Some degree of deafness is common in all types of mucopolysaccharidoses. It can be conductive deafness, deafness associated with a lesion auditory nerve(sensory deafness), or a combination of both types of deafness. Deafness is exacerbated by frequent ear infections. Hearing tests (audiometry) should be performed regularly in order to start treatment immediately and maximize the ability to learn and communicate. Both sensorineural and conductive hearing loss in most cases can be compensated by the selection of hearing aids.

The cardiovascular system

Characterized by thickening of the valves, narrowing of the arteries, increasing myocardial rigidity, cardiomyopathy, arterial hypertension. With age, heart failure can develop.

Almost all patients with MPS I have pathology of cardio-vascular system, which is characterized by thickening of the myocardium, a decrease in the contractility of the heart muscle, changes in the valvular apparatus and sealing of the cusps and chords of the valves, leading to the formation of heart defects. Valvular heart disease can progress over many years without visible clinical manifestations. If the patient's condition worsens, surgery to replace damaged valves. Since heart problems are common in patients with MPS I, in order to prevent possible complications they need to have an echocardiogram every year.

In a severe form of the syndrome, due to accumulations of GAGs, damage to the heart muscle can develop - cardiomyopathy. The heart can also become overloaded due to having to pump blood through the altered lungs, an abnormal enlargement of the right side of the heart, or right-sided heart failure. Some patients have high blood pressure.

Leather

In MPS I, the skin is thick and tough, making it difficult to draw blood and use intravenous catheters. Some have hair on the face and back. Profuse sweating and cold hands and feet are common, possibly due to disorders of the cardiovascular system or body temperature regulation mechanisms. When these symptoms appear, an examination by a cardiologist is necessary.

Nose, throat, chest and ear problems

Many patients with MPS I have noisy breathing due to swelling and thickening of the upper mucous membranes. respiratory tract and shortening of the trachea. Often children suffer from chronic rhinorrhea (runny nose) due to anatomical features the structure of the nasal passages (they have shorter posterior nasal passages) and hypertrophy of the mucous membranes.

The tonsils and adenoids are often enlarged and may partially block the airways. The neck is usually short, which contributes to the development of breathing problems. The trachea is often narrowed by mucus buildup, often more flexible and soft due to the malformation of the cartilage rings in the trachea. The shape of the chest in patients with MPS I is irregular, the connection between the ribs and the sternum is not as elastic, so the chest is stiff and cannot move freely, in turn preventing the lungs from taking in a large amount of air. This causes recurring bronchitis and pneumonia.

Many patients have noisy breathing even when there is no infection. At night, they may have restless sleep and snoring. Occasionally, the patient may experience sleep apnea for short periods, such 10 to 15 second pauses in breathing are not very dangerous, but it frightens parents, as they believe that the child is dying. If parents notice a significant violation of the rhythm of breathing, suffocation in a child, they should consult a specialist who will assess the child's condition. In some cases, sleep apnea is treated by removing the tonsils and adenoids, ventilating the airways with continuous or two-level positive pressure, or performing a tracheostomy (surgery to cut the anterior wall of the trachea, followed by the introduction of a cannula into its lumen or the creation of a permanent hole - a tracheostomy).

Many families try to avoid tracheostomy as this is an invasive procedure that interferes with the child's normal activities. In fact, many doctors believe that patients with MPS I should have a tracheostomy earlier than usual. Such patients feel much better after improved breathing during sleep.

Gastrointestinal system

Hepatosplenomegaly in Hurler and Hurler-Scheie syndromes (enlarged liver and spleen due to accumulation of mucopolysaccharides)). In Scheye's syndrome, the liver may also be enlarged. Enlargement of the liver usually does not impair its function, but it can affect the tolerance of a particular food, and can also contribute to the deterioration of respiratory function.

In MPS I, the abdomen is enlarged due to specific posture, muscle weakness, and an enlarged liver and spleen. Characteristic are defects in the anterior abdominal wall in the form of combined or isolated hernias (umbilical, inguinal, inguinal-scrotal and ventral). An inguinal hernia needs to be operated on, but sometimes it recurs after surgery. Umbilical hernias are usually not operated on, intervention is performed only in cases where the intestinal loop is infringed or the hernia becomes very large.

Patients with MPS I often have unstable stools. In the forms of Gurler-Sheye and Sheye, abdominal pain often occurs. Diarrhea may disappear with age, but may reappear while taking antibiotics. Chronic constipation develops with age as a child with MPS I becomes less active and their muscles weaken.

The human foot is the main link in the support of the body. The area of ​​the foot is approximately 1% of the total body surface. But it is she who is subject to the main load, equal to the weight of the human body. The foot has several functions: balancing, supporting, cushioning. Under the influence of various factors, its arch is subject to deformation, a disease such as transverse flatfoot. As a result, the sole worsens its cushioning properties, which is accompanied by various complications.

• • Classification of foot injuries
  • Symptoms of the disease
• Longitudinal flatfoot
• Differences in children's flat feet

• What is the danger of flat feet?
• Prevention of flat feet in adults and children

What is flatfoot? General information

human foot consists of 26 bones, which are connected to each other by ligaments and joints, for the movement of which the muscles and tendons are responsible. The foot of a healthy person has two arches: longitudinal and transverse, which are located in the area of ​​\u200b\u200bthe inner edge of the sole and the bases of the fingers. While walking, a person does not fully rest on the foot. Usually 3 points work: the area of ​​\u200b\u200bthe thumb and the base of the little finger, as well as calcaneus. If the muscles and ligaments of the foot weaken, then its shape begins to change, which eventually becomes flat. While walking, a person has to rest the sole completely on the surface. As a result, shock-absorbing properties worsen, flat feet appear.

The arches work like levers or springs, creating comfortable movement with minimal consequences for the body. Damage to this area will disruption of the entire system, and, as you know, the body is a single whole. Any changes in the operation of one system will certainly affect the operation of another. Flat feet can lead to spinal deformity, damage to the knee and femoral ligaments. When the foot cannot cope with its tasks, they move to the organs that are higher. The hips, knees and spine are not adapted to this load, so they wear out quickly.

Classification of foot injuries

The foot has 2 arches. Therefore, the classification of the forms of the disease is quite logical - transverse and longitudinal flat feet. There is also a combined variant of the disease.

The classification of the disease also includes definition of congenital and acquired flat feet. The latter case is very rare and appears as a result of abnormal development of the fetus. Acquired flat feet manifest at any age. Moreover, it is divided into several types:

• rickets (appears due to lack of vitamin D);
• static (appears due to a decrease in muscle tone);
• traumatic (occurs due to fractures and damage to bones);
• paralytic (appears due to polio).

Symptoms of the disease

Symptoms of flat feet appear gradually. The first symptom of the disease is strong pain in the legs at the end of the working day. By evening, the legs and soles swell, convulsions often occur. It is difficult for women to walk in high shoes. Due to the increase in the size of the foot, old shoes should be discarded and purchased in a larger size. Over time, the pain syndrome moves higher, to the hip and knee joints. These symptoms are not only an indicator of flat feet. Signs of a similar nature also occurs with varicose veins but the treatment of this disease is completely different.

Flat feet is a serious disease that is characterized by deformity of the foot. In everyday life, few people pay attention to this defect. Knowing the features of flat feet is necessary in order to take timely measures to correct it. The causes of the disease are either internal or external. Given the modern pace of human life and neglect of your wardrobe, often flatfoot has a mixed shape. Even your favorite sneakers can provoke flat feet, as their soles have excellent cushioning. Sneakers take on the entire load, securing the heel. As a result, the muscles weaken, all the prerequisites for the development of flat feet appear.

From internal causes diseases, it is necessary to identify several provoking factors. First of all, it is the presence of concomitant diseases. Among them, the first place is rheumatoid arthritis. It affects the ligaments and cartilage responsible for supporting the foot. Mechanical damage and leg injuries also contribute to the development of flat feet.

Action external causes It is very easy to prevent if you take care of your health and choose your shoes carefully. Among the exogenous factors diseases can be classified as:

• insufficient activity;
• wrong shoes;
• pregnancy and hormonal disorders.

Longitudinal flatfoot

With this type of flat feet, the foot increases in length due to the lowering of the longitudinal arch. As a result, the sole completely touches the floor. The main symptom of the pathology is a decrease in the gap between the floor surface and the inner edge of the foot. People with this diagnosis gradually develop clubfoot.

There are 3 stages of longitudinal flat feet:

With this type of flat feet, the length of the foot becomes shorter, middle finger deformed, large deviated. A bump-shaped seal forms at the base of the first finger.

There are 3 stages of transverse flatfoot. Transverse deformation is classified angle of deviation of the big toe on the sole of the feet.

• The first stage is a mildly pronounced transverse flat foot. Symptoms of the disease appear with the progression of the disease. Deviation of a finger no more than 20 hail. Pain after physical activity.
• At the second stage, the deviation of the finger is already 35 degrees. When loaded, there is a burning sensation in the area of ​​​​the sole.
• The third stage of the disease is characterized by constant pain. Deviation of the finger more than 35 degrees. Some people may develop bursitis.

Differences in children's flat feet

The leg of children under 5 years old is fragile and is in the process of formation. Therefore, adults have a huge responsibility. They are obliged to prevent the disease, recognize it in time and treat it.

There are some points that adults must pay attention to:

• complaints of children about pain in the legs after active games;
• unevenly worn shoes;
• the arches of the feet became more dense.

If the child began to move less, the gait has changed, then you need to consult with an orthopedist. The doctor can identify flat feet at an early stage. Treatment and symptoms this disease children almost do not differ from adults. There is only one feature, it is reversibility of pathology. With gradual maturation, a natural disposal of flat feet occurs. The leg is fully formed at the age of 14. Until this time, you need to focus on physical activity (walking, running). So, the muscles will develop correctly, and the foot will receive a normal shape.

Many people do not pay attention to flat feet, ignore the first signs. In fact, this is a fairly rapidly developing and serious pathology, almost untreatable. Flat feet can be completely cured only in childhood until the foot is fully formed.

In adults, treatment is aimed at slowing the progression of the disease and prevention of related complications. Treatment of flat feet is complex. Progressive transverse/longitudinal flat feet are stopped for the patient, pain syndrome is eliminated, muscles are strengthened. The treatment and symptoms of these types of disease are almost the same. Next, consider in more detail modern ways treatment.

Medications along with physiotherapy can relieve pain. The patient is prescribed systemic analgesics (Aspirin, Ibuprofen), as well as ointments for local use (Voltaren, Dolgit).

The therapy is based on physiotherapy. A set of classes is chosen by an orthopedist, taking into account the age of the patient and the stage of the disease. A great healing effect has a foot massage. Regular procedures will help increase muscle tone, normalize blood circulation. Alas, all of the above methods of treatment are effective only at the initial stage of the disease. With significant deformities of the foot, only one way can help - surgery.

The treatment of flat feet in children needs a different approach. As a rule, longitudinal flat feet are determined in children (that this deformation should not be left without due attention, all parents must know). With timely detection of flat feet, it responds well to treatment. Incidentally, the muscles and ligaments of children are susceptible to conservative treatment. A positive result is given by massage and exercise therapy. If children have congenital flat feet, then its treatment begins from the moment of birth, for which special splints and bandages are used.

What is the danger of flat feet?

The human body works as a whole. Between all organs there are both functional and anatomical connections. During flat feet appears center of gravity shift. To maintain balance, a person needs to deviate in the opposite direction all the time. After a certain time, the deformation increases, and the back is significantly rounded. Flat feet and poor posture have similar developmental symptoms. This is muscle and connective tissue weakness, as well as obesity. At healthy people The feet act as a shock absorber. During flat feet, it is lost. As a result, a large load is placed on the knees and spine, which leads to an even more pronounced curvature of posture.

Foot deformity can lead to appearance of other complications, among which:

• curvature of the fingers;
• clubfoot;
• ingrown nails;
• dystrophic changes in the legs;
• heel spurs.

Also, in children with this diagnosis, depreciation of the foot is impaired. As a result, the vibration of the body during movement passes to the spine and lower legs. Joint irritation can lead to inflammatory processes arthrosis appears. The impact of foot deformity on the spine affects its curvature. The child is constantly tormented by pain in the head and legs, his school performance and ability to work are deteriorating.

Prevention of flat feet in adults and children

To prevent the appearance of flat feet, it is necessary to periodically do its prevention. For starters, orthopedists advise pay attention to shoes. Now in almost any store you can buy special orthopedic insoles and shoes. The choice of these products for children is simply amazing in its diversity. Do not forget that insoles and shoes will not be able to cure foot deformity. They only prevent the appearance of flat feet.

To strengthen muscle tissue, it is useful to use contrast baths. You need to take turns dipping your feet in basins of hot and cold water . In addition, regular intake of natural microelements (calcium, selenium, copper) and vitamins (A, E, C, D) will contribute to muscle strengthening.

The treatment of such a disease as transverse flatfoot is based only on individual features human: involvement in the process of blood vessels, changes in the phalangometatarsal joints, the intensity of the pain syndrome, etc. So, the treatment tactics can differ significantly in different people, this requires professional intervention and absolutely excludes self-treatment.

The sunken chest (hollow chest, pit, shoemaker's cage) in men is characterized by serious clinical changes. It is accompanied by cosmetic defects that can only be corrected by surgical methods.

The fossa on the sternum in men negatively affects the figure. Due to such changes, psychological complexes are formed in a teenager during puberty. At the age of 14-17 effective treatment disease cannot be carried out, since the ribs and spine have not yet completed their formation. After 20 years, cartilage structures are replaced by bone structures due to the deposition of calcium salts in them.

The condition is dangerous not only with cosmetic defects, but also with a malfunction internal organs. Improper functioning of the lungs, frequent colds and disorders heart rate- common consequences of the disease.

How pathology is formed in children

A sunken chest occurs in 0.001% of the population. Pathology belongs to the category of congenital. It is associated with hyperplasia of the bone and cartilage structures of the ribs and sternum. Due to the violation of the formation of the bone and cartilage structure, a peculiar shape of the breast occurs. It flattens in the anterior-posterior and liver direction. A dimple in the sternum (depression) is inherited and is common in men.

The disease is provoked by the accelerated growth of ribs and cartilage. Deformation is asymmetric, and its degree of severity fluctuates significantly.

A hollow in the chest causes negative changes in the internal organs. A concave chest leads to increased pressure on the heart and lungs. Respiratory function lung tissue is disturbed against the background of pathology, which leads to an increase in the frequency respiratory movements and heart rate.

Pathological changes in the bronchial tree lead to frequent inflammation in the lungs, colds and painful sensations in the chest.

West chest in a newborn, it can be detected not immediately after birth, but after a few weeks. When the bone-cartilaginous skeleton gets stronger, its structure can be clearly seen during external examination.

If a pit is found on the sternum in a newborn, treatment of the pathology should be started immediately. In the initial stages, exercises, physiotherapy, massage, wearing orthoses will help prevent the formation of a breast funnel.

Exercises

Exercises to eliminate the funnel chest in a newborn are prescribed to correct sunken deformity. So, strengthening the pectoral muscles will help correct the pathology. It is important that a qualified specialist is engaged in physiotherapy exercises with the baby.

Exercises for sunken chest should provide expansion of the chest cavity. When they are performed great importance should be given to breathing exercises. Aerobic exercise and breathing procedures combined with cycling, swimming, skiing effectively expand the chest and push the intercostal joints apart.

Gymnastics for a concave sternum allows you to straighten the spinal column and eliminate the curvature of the ribs.

Therapeutic gymnastics in a newborn child should be aimed at training the respiratory muscles. Gymnastic exercises for a child can be as follows:

• put the baby on your stomach. Press his legs to your chest and return to the starting position. The number of repetitions - 5-10 times;
• take and spread the child's arms to the sides and return them to the chest. The number of repetitions - 5-10 times;
• a one-year-old child with a concave chest should be allowed to hold toys in his hands in order to strengthen the muscular frame of the back.

After receiving positive results you can increase the frequency and amplitude of movements.

Retraction of the sternum in a baby is best treated on early dates. If the disease persists until school years, it will provoke defects in the appearance of the child.

The fossa of the sternum in a newborn child adversely affects the development of the body. Over time, the pathology leads to compression of the heart and lungs. Against this background, the baby has frequent colds, pneumonia, congestive changes in the chest cavity. And with the growth and development of the body against the background of the disease, a curvature of the spinal column will begin to form.

Therapeutic tactics that are used in case of illness should not only be aimed at removing deformed cartilage and ribs, separating the intercostal muscles from the sternum and correcting its concavity. In the initial stages, exercises are used that are aimed at restoring the tone of the skeletal muscles.

However, with the help of therapeutic exercises and physiotherapy, one can only prevent the progression of the disease. Surgical intervention is necessary to eliminate the retraction. Consider the methods surgical treatment deformities of the chest and ribs.

Operational Methods

With a depressed chest in men, specialists usually use the following surgical techniques:

• minimally invasive Nass method - used for about 10 years. Today there is no safer and more effective alternative to this method. It is based on the introduction of metal plates that correct the chest defect. In men, they are set for 3-4 years, and in children of school age - for a longer period;
• thoracoplasty according to Urmonas, Ravich and Kondrashin - allows you to normalize the state of the costal-sternal joint without the use of artificial fixators;
• surgery using external fixators according to Bairov, Gafarov, Marshev, Gross - belongs to the category of magnetosurgical corrections. The technique involves the use of external fixators;
• rotation of the sternum at an angle of 180 degrees or a coup on a muscular leg according to the Taguchi method - involves the preservation of the vascular bundle;
• with a depressed chest of the 1st-2nd degree, artificial implants can be used to eliminate curvature of the sternum and ribs;
• the installation of internal fixators by the Timoshchenko and Rekhbein operative method can significantly reduce the patient's rehabilitation time, but when using this method, repeated access to the chest cavity is difficult.

In children surgery possible only after 6 years. Until this time, the sunken chest is treated conservatively.

• Chondrodystrophy
• Hurler syndrome

Such diseases of the skeletal system as, for example, chondrodystrophy and gargoylism are quite rare, and information about them is still insufficient. In this article, we will try to highlight the causes, diagnosis and treatment of these serious ailments.

General information about chondrodystrophy

This disease affects primarily the base of the skull, as well as the lower and upper limbs. It is systemic and congenital in nature, modifies the skeleton and prevents it from fully developing even at the embryonic stage. The defect begins its development in the mother's womb (3-4 weeks of pregnancy). The body of the patient has a normal size, and the limbs are shortened.

The reasons

Most doctors agree that the disease is hereditary. Improper ossification leads to impaired bone growth. The epiphyses of long bones of a tubular shape are affected. An interesting fact: bones grow in thickness as usual. When examining the x-ray, you will easily notice that the bones appear somewhat thickened. This is an appearance, they are just short.

Clinical picture and diagnosis

Characteristic signs of the disease are shortening of the hip and shoulder. In children, the real problems with deformity begin after they learn to walk.

Other signs:

In the event of an illness being detected in early stage fetal maturation, doctors recommend a caesarean section.

It is impossible to cure chondrodystrophy, because effective therapy does not exist. There are no endocrinological drugs that normalize bone growth in the child's body.

The patient's suffering is alleviated by orthopedic therapy, based on the prevention of deformity through corrective operations and the use of specially designed drugs. Limb lengthening by surgery does not solve the problem, since the picture of the disease remains unchanged. In addition, the operation is extremely painful.

Hurler syndrome

This pathology is also known as "gargoylism" and is caused by a violation of the metabolism of mucopolysaccharides and lipids. The disease is quite rare and is hereditary. In the organs (connective tissue), heparan sulfate and dermatan sulfate accumulate. Serious metabolic disturbances begin. Mucopolysaccharides are concentrated in the retina, brain, peripheral nerves, spleen, liver and other organs.

Clinical picture

The patients are often children. They are short, have a steep forehead, an enlarged skull, a sunken nose root, a large tongue, thick lips, a special facial expression, limited mobility, a short neck, and a number of other external features. The patient's hand remotely resembles a trident. The abdomen and buttocks are protruded.

The following changes are observed in the organs:

• hepatosplenomegaly;
• diffuse clouding of the cornea;
• umbilical hernia;
• deafness;
• hypertrichosis.

In addition, traced:

• hoarse voice;
• dementia;
• dental caries;
• hard and dry hair;
• nail problems.

In the vast majority of cases, heart failure occurs. The endocardium and myocardium, valves, arteries are changing. The size of the heart is abnormally enlarged.

Diagnostics

• prenatal diagnosis. An enzymatic analysis of the cells of the amniotic fluid is done. After the birth of a child, diagnostic difficulties do not arise. Pathological mucopolysaccharides are found in the patient's urine.
• X-ray examination. Changes are immediately visible: the skull is enlarged, cranial sutures close prematurely, hydrocephalus may occur. Characterized by dolichocephaly. Pronounced jaw deformity. The lumbar vertebrae are damaged.
• Laboratory research. A biochemical blood test does not always give the desired result.
• Differential diagnosis. Practically not required. Patients suffering from gargoylism are strongly distinguished by external signs.

Treatment methods are very specific:

• surgical correction of glaucoma;
• stem cell transplant;
• correction of heart failure.

At arterial hypertension vasodilators are prescribed. With a diagnosis of "valvular dysfunction" (severe form), prosthetics are recommended. When a valvular lesion is fixed, infective endocarditis is prevented. Also used hormonal preparations(thyroid hormones, ACTH). Symptomatic treatment involves taking enzymes, vascular preparations, hepatoprotectors and vitamins.

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Related to lysosomal storage diseases. It is characterized by a deficiency of alpha-L-iduronidase, an enzyme of lysosomes involved in the catabolism of acid mucopolysaccharides, which form the basis of the intercellular substance of connective tissue.

Hurler syndrome is one of the representatives of the group of mucopolysaccharidoses, united by the term gargoylism .

History reference

The disease, originally named Pfaundler's disease - Hurler, first described by two pediatricians: Austrian - German. Hurler Gertrud(1889-1965) and German - German. Pfaundler Meinhard von (1872-1947) .

The disease described by the authors manifests itself in the first months of life with coarse facial features (gargoylism), hepatosplenomegaly, stiffness of the joints, and deformity of the spinal column. Then the American ophthalmologist Sheye, Eng. H. G. Scheie(1909-1990) described a second form of the disease with a later onset and a more benign course, called Scheye syndrome. Later, an intermediate form of the disease was described, called Hurler-Scheie syndrome .

Eponym

The disease is named after one of the discoverers, an Austrian pediatrician. Gertrud Gurler(German Gertrud Hurler), (1889-1965) .

Epidemiology

Hurler syndrome occurs with a frequency of 1 in 100,000.

Inheritance

This group of diseases is inherited, like the vast majority of lysosomal storage diseases, in an autosomal recessive mode of inheritance. Thus, it occurs with the same frequency in both men and women.

see also

Write a review on the article "Hurler Syndrome"

Notes

1. (English) . Mucopolysaccharidoses. ninds.nih.gov. Retrieved November 30, 2014.
2. James, William D.; Berger, Timothy G.; et al. Andrews" Diseases of the Skin: clinical Dermatology. - Saunders Elsevier, 2006. - ISBN 0-7216-2921-0.(English)
3. . Chapter 316. med-books.info. Retrieved November 30, 2014.
4. . Gurler syndrome. psychology_pedagogy.academic.ru. Retrieved November 30, 2014.
5. Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. Dermatology: 2-Volume Set. -St. Louis: Mosby, 2007. - ISBN 1-4160-2999-0.(English)
6. (English) . en-de-fr.com.ua. Retrieved November 30, 2014.
7. on Who Named It? (English)
8. Hurler, G. (1919). "Über einen Type multipler Abartungen, vorwiegend am Skelettsystem". Zeitschrift fur Kinderheilkunde 24 : 220–234. (German)
9. (English) on the EMedicine website
10. . Gurler syndrome (gargoylism). medpractik.ru. Retrieved December 13, 2014.

Literature

• G. Hurler. Uber einen Typ multipler Abartungen, vorwiegend am Skelettsystem. Zeitschrift fur Kinderheilkunde, Berlin, 1919; 24:220-234. (English)
• M. Pfaundler. Demonstrationen Uber einen Typus kindlicher Dysostose. Jahrbuch fUr Kinderheilkunde und physische Erziehung, Berlin, 1920; 92:420.
• H. G. Scheie, G. W. Hambrick Jr., L. A. Barnes. A newly recognized form of fruste of Hurlers disease (gargoylism). American Journal of Ophthalmology, 1962; 55:753-769. (English)

An excerpt characterizing Hurler Syndrome

Hurler syndrome(Pfaundler's disease - Hurler, mucopolysaccharidosis-I H, English MPS-I H) is a severe hereditary disease from the group of mucopolysaccharidoses related to lysosomal storage diseases. It is characterized by a deficiency of alpha-L-iduronidase, an enzyme of lysosomes involved in the catabolism of acid mucopolysaccharides, which form the basis of the intercellular substance of connective tissue.

Hurler syndrome is one of the representatives of the group of mucopolysaccharidoses, united by the term gargoylism.

History reference

The disease, originally named Pfaundler's disease - Hurler, first described by two pediatricians: Austrian - German. Hurler Gertrud(1889-1965) and German - German. Pfaundler Meinhard von (1872-1947).

The disease described by the authors manifests itself in the first months of life with coarse facial features (gargoylism), hepatosplenomegaly, stiffness of the joints, and deformity of the spinal column. Then the American ophthalmologist Sheye, Eng. H. G. Scheie(1909-1990) described a second form of the disease with a later onset and a more benign course, called Scheye syndrome. Later, an intermediate form of the disease was described, called Hurler-Scheie syndrome.

Eponym

The disease is named after one of the discoverers, an Austrian pediatrician. Gertrud Gurler(German Gertrud Hurler), (1889-1965).

Epidemiology

Hurler syndrome occurs with a frequency of 1 in 100,000.

Inheritance

This group of diseases is inherited, like the vast majority of lysosomal storage diseases, in an autosomal recessive mode of inheritance. Thus, it occurs with the same frequency in both men and women.

Autosomal recessive inheritance in practice means that the defective gene is located on one of the two allelic autosomes. The disease clinically manifests only when both autosomes, received one by one from the father and mother, are defective for this gene. As in all cases of autosomal recessive inheritance, if both parents carry the defective gene, then the probability of inheriting the disease in the offspring is 1 in 4. Thus, on average, there are three affected children in such a family without clinical signs of manifestations of the gene disease. In the diagram, blue indicates healthy, purple - carriers of the defective gene, red - Hurler syndrome (two defective genes of the same allele). A blue circle indicates a normal gene, a red circle indicates a defective one.

Classification

According to International classification diseases of the tenth revision (ICD-10), there are:

• E76 76. Disorders of glycosaminoglycan metabolism:
  • E76.0 76.0 Mucopolysaccharidosis, type I. Syndromes: "Gurler" (MPS-I H), "Sheye" (MPS-I S), "Gurler - Sheye" (MPS-I H/S).

Clinical picture

Children with Hurler syndrome are characterized by short stature (lagging behind in physical development is observed from the end of the first year of life). Signs of gargoilism are characteristic: a large skull, a steep forehead, a sunken bridge of the nose, thick lips, a large tongue, a characteristic facial expression (“ water spitting face"). In addition, there is a short neck, limited mobility of the joints (stiffness mainly affects the elbow and interphalangeal joints of the fingers and toes), fixed kyphosis at the junction of the thoracic vertebrae to the lumbar vertebrae, shortening of the limbs, mainly occurs due to the proximal sections (hips and shoulders), to a lesser extent - shins and forearms. The structure of the patient's hand is very peculiar: the fingers are short, the same in length ( isodactyly) diverge fan-shaped, resembling a trident. Lower lumbar lordosis contributes to the protrusion of the abdomen forward, and the buttocks back. There is hepatosplenomegaly, a tendency to form an umbilical hernia. Diffuse opacification of the cornea due to the accumulation of dermatan sulfate in it is characteristic. May develop dementia, dental caries, characteristic form watch-glass nail plates, hearing loss or deafness, low hoarse voice, hypertrichosis, dry and coarse hair. In most cases, the heart is involved in the pathological process - it increases in size, changes in valves, myocardium, endocardium, large and coronary arteries. X-ray examination is determined by premature ossification of the lambdoid suture, expansion of the Turkish saddle, pathological shape of the vertebrae (" fish vertebrae"), curvature radius, deformations of the metaphyseal and epiphyseal parts of the long tubular bones, short metacarpal bones and phalanges of fingers. There is also a progressive mental retardation. Such children usually do not live past the age of 10.

Catad_tema Cystic fibrosis and other fermentopathies - articles

ICD 10: E76.0

Year of approval (revision frequency): 2016 (review every 3 years)

ID: KR380

Professional associations:

• Union of Pediatricians of Russia

Approved

Union of Pediatricians of Russia

Agreed

Scientific Council of the Ministry of Health Russian Federation __ __________201_

Keywords

• Alpha-L-iduronidase;
• Glycosaminoglycans;
• Children;
• Mucopolysaccharidosis;
• Hurler's syndrome (mucopolysaccharidosis I H - severe form);
• Hurler-Scheie syndrome;
• Sheye's syndrome (mucopolysaccharidosis I S - mild form);
• Enzyme replacement therapy.

List of abbreviations

ALT - alanine aminotransferase

AST - aspartate aminotransferase

GAGs - glycosaminoglycans

CT - CT scan

LDH - lactate dehydrogenase

CPK - creatine phosphokinase

MPS - mucopolysaccharidosis

MRI - magnetic resonance imaging

TCM - bone marrow transplant

Ultrasound - ultrasonography

FVD - function external respiration

ERT - enzyme replacement therapy

AP - alkaline phosphatase

ECG - research

EMG - electromyography

ENMG - electroneuromyography

Echo-KG - echocardiography

EEG - electroencephalography

Terms and Definitions

Enzyme Replacement Therapy- treatment consisting in the life-long administration of the drug (recombinant enzyme) to patients with a congenital metabolic defect.

1. Brief information

1.1 Definition

Mucopolysaccharidoses (MPS)- a group of hereditary metabolic diseases associated with impaired metabolism of glycosaminoglycans (GAGs), leading to damage to organs and tissues. These diseases are caused by mutations in genes that control the process of intralysosomal hydrolysis of macromolecules.

Mucopolysaccharidosis type I - hereditary lysosomal storage disease caused by a deficiency of the alpha-L-iduronidase enzyme and occurring with various clinical manifestations: growth retardation, mental retardation, damage to the nervous system, cardiopulmonary disorders, hepato-splenomegaly, multiple dysostoses, corneal clouding. All of the above symptoms lead to disability, and in severe cases of the disease - to death.

1.2 Etiology and pathogenesis

It consists in the accumulation of various types of GAGs, characterized by somatic manifestation in the form of facial dysmorphism, hepatosplenomegaly, damage to the heart, respiratory system, skeletal changes, neurological symptoms, hematological and ophthalmic changes. MPS variability is determined by the type of accumulated substrate with insufficient degradation of GAGs (heparan sulfate, keratan sulfate, dermatan sulfate).

Pathology is caused by a heterogeneous group of mutations in the gene encoding the lysosomal enzyme alpha-L-iduronidase. Deficiency of alpha-L-iduronidase can lead to the development of various disease phenotypes, causing differences in the severity of symptoms. There are currently three phenotype diseases:

Hurler's syndrome (mucopolysaccharidosis I H - severe form),

Scheye's syndrome (mucopolysaccharidosis I S - mild form),

Hurler-Scheie syndrome (mucopolysaccharidosis I H / S - intermediate form).

Type of inheritance: autosomal recessive. Gene IDUA, encoding alpha-L-iduronidase is located in the chromosomal region 4p16.3.

1.3 Epidemiology

It occurs with a population frequency of 1:40,000 - 1:100,000 newborns.

MPS I H Hurler syndrome occurs, according to various sources, with a population frequency of 1:40,000 - 1:100,000 newborns.

MPS I H/S Hurler-Scheie syndrome occurs with a population frequency of 1:40,000 to 1:100,000 newborns; MPS I S Scheye syndrome - 1:100,000 newborns.

1.4 ICD-10 coding

E76.0 Mucopolysaccharidosis type 1

1.5 Examples of diagnoses

• Mucopolysaccharidosis type I Hurler-Scheie syndrome. Mental retardation of a mild degree with underdevelopment of speech of the 2nd level. Dyslalia. Secondary cardiomyopathy. II degree aortic valve insufficiency, pulmonic valve insufficiency and mitral valve I degree. NC I-II degree. Spinal dysplasia, total form. Instability of the cranial spine. Spinal canal stenosis without spinal cord compression at the level of C1-C3 vertebrae. Funnel chest deformity II st. Kyphoscoliosis I-II Art. Spina bifida L4-L5-S1. Coxa valga. Multiple contractures of large and small joints. Deformity of the ankle joints. Somatic growth retardation. Adenoids II-III degree. Hypertrophy of the tonsils II degree. diffuse keratopathy. Clouding of the cornea. Thickening of the retina. Densification of the lens. Umbilical hernia
• Mucopolysaccharidosis type I (Cheye syndrome). Violation of the posture of the scoliotic type. Osteochondropathy cervical spine. Contracture of the knee joints. Contracture of the wrist joints. Carpal syndrome on both sides. Condition after surgical treatment. Secondary cardiomyopathy. Mitral valve insufficiency. Myxomatosis of the mitral valve leaflets. Partial violation cognitive functions. OU hyperopic astigmatism of the reverse type, keratopathy, epitheliopathy 2-3 tbsp.
• Mucopolysaccharidosis type I (Hurler disease). Cervical hyperlordosis. Right-sided thoracic scoliosis II-III degree. Keeled deformity of the chest. Multiple contractures of the upper and lower extremities. Valgus deformity of the lower extremities with the apex at the level of the knee joints. Planovalgus deformity of the feet II degree. Secondary cardiomyopathy. Myxomatosis of the mitral valve leaflets, mitral valve insufficiency of the 2nd degree, aortic valve insufficiency. NK I-IIA Art. Sinus node dysfunction Exophthalmos, corneal clouding medium degree. Hypermetropia low degree. Ptosis 1 st. Tempo Delay speech development. carpal tunnel syndrome. Dysarthria. Umbilical hernia.

1.6 Classification

In accordance with the deficiency / absence of metabolic lysosomal enzymes and the corresponding gene defects, and the severity of clinical symptoms, the following types of mucopolysaccharidoses are distinguished:

Table 1– Classification (nomenclature) of the Ministry of Railways

According to enzymatic defects, 3 types of mucopolysaccharidosis type I are distinguished:

• MPS I H Hurler syndrome;
• MPS I H/S Hurler-Scheie syndrome;
• MPS I S Scheye syndrome.

1.7 Clinical picture

Synonyms: Hurler syndrome, Pfaundler-Hurler syndrome.

The main clinical manifestations: coarse facial features, mental retardation, clouding of the cornea, joint stiffness.

Appearance. In a newborn, characteristic manifestations are not noted, symptoms most often develop in the first year (from 6 months, sometimes later, from 18 months) and are manifested by growth retardation (maximum growth is about 110 cm), which completely stops by 2-5 years. With short stature, children have a proportional physique, short neck, scaphocephaly, macrocephaly, coarse facial features, puffy lips, wide nostrils, sunken nose bridge, eye hypertelorism, small sparse teeth, macroglossia.

Also found: hypertrichosis, hepatosplenomegaly, hearing loss, umbilical and / or inguinal hernia. In the later stages, children are diagnosed with deafness, blindness, and profound dementia.

Skeletal system: wide chest, decreased mobility in large and small joints, thoracolumbar kyphosis with hump formation. Orthopedic complications lead to pain and immobility.

Central nervous system. At spinal cord compression caused by thickening of its membranes or instability of the atlantoaxial joint, note: gait disturbance, muscle weakness, clumsiness with preserved motor skills, and bladder dysfunction.

In severe disease, there are often convulsions, which requires an assessment of the neurological status. In patients with mild clinical signs, seizures are much less common. The progression of the disease is accompanied by generalized tonic-clonic paroxysms, which usually respond well to anticonvulsant monotherapy.

Carpal tunnel syndrome is a common compression neuropathy in patients aged 5 to 10 years and adults. If left untreated, it can lead to irreversible contracture of the distal interphalangeal joints, as well as impaired or loss of sensitivity of the first three fingers and paresis of the tenar muscles. Unfortunately, patients rarely report pain until loss of function occurs.

Behavioral disorders: Cognitive regression along with severe hearing loss, lack of sleep caused by obstructive sleep apnea, have a significant impact on the child's behavior. As cognitive deficits increase, autistic traits join hyperactivity and aggressiveness. Drug therapy aimed at controlling destructive behavior is often ineffective. Psychomotor development is normal or moderate mental retardation is noted.

Respiratory organs: frequent respiratory diseases in the form of rhinitis, otitis. The accumulation of GAGs in the tonsils, epiglottis, and also in the trachea leads to thickening and narrowing of the airways and the development of obstructive sleep apnea.

Organs of vision: clouding and pigmentary degeneration cornea, glaucoma.

Cardiovascular system: characterized by thickening of the valves, narrowing of the arteries, increasing myocardial stiffness, cardiomyopathy, arterial hypertension. With age, heart failure can develop.

Gastrointestinal system: hepatosplenomegaly.

Synonyms: Scheye's syndrome, mucopolysaccharidosis type V, late Hurler's disease, cellular metachromasia, Shpet-Hurler syndrome, Ullyarich-Scheie's syndrome, Morquio's dysostosis with corneal opacity, hereditary osteoarthropathy with recessive inheritance, late form of Pfaundler-Hurler's disease, Schinz (Schinz) syndrome .

Main clinical manifestations: wide mouth, full lips, early clouding of the cornea.

Appearance. The first signs of the disease appear at the age of 3-5 years. Patients with a hypersthenic physique with highly developed muscles, coarse facial features, a wide mouth with full lips, lower prognathia are characteristic. Thickening and tension of the skin on the fingers. Gradually develops limitation of movement in the joints upper limbs. All the symptoms of the disease become most pronounced by the period of puberty. Perhaps increased hairiness, a short neck.

Skeletal system: there is a slight growth retardation. Multiple dysostosis is mainly represented by stiffness and soreness of the joints of the hands and feet, the formation of a "clawed paw" and a hollow foot, hallux valgus knee joints. Carpal tunnel syndrome often develops, which, along with stiffness, leads to limited function of the upper extremities. Dysplasia of the facial skull. Rarely - congenital clicking 1 finger.

Respiratory organs: frequent respiratory diseases in the form of rhinitis, otitis media. Perhaps the development of obstructive respiratory diseases, sleep apnea.

Organs of vision: there is an early uneven clouding of the cornea. In the future, usually after 30 years, glaucoma develops, retinitis pigmentosa. Rarely - edema of the optic disc.

Central nervous system: psychomotor development is normal or slightly delayed. Perhaps the development of carpal tunnel syndrome (carpal tunnel syndrome) due to compression of the median nerve, which is accompanied by paresthesia in the III-IV fingers of the hand and atrophy of the tenar muscles.

Cardiovascular system: characteristic defects of the aortic valve, coarctation of the aorta, mitral stenosis.

Gastrointestinal system: inguinal-scrotal and umbilical hernias are noted, infrequently - hepatosplenomegaly.

Clinically, it is very difficult to differentiate between Scheye and Hurler syndromes. Biochemical studies play a key role in establishing the diagnosis. With Scheye syndrome in the urine of patients in in large numbers dermatan sulfate is detected.

Synonyms: Gurler-Scheie syndrome.

The main clinical signs: joint stiffness, short stature, corneal clouding.

Appearance: the first symptoms of the disease appear by the age of 3-8 years. Characteristic: scaphocephaly, macrocephaly, sunken bridge of the nose, puffy lips, clouding of the cornea, micrognathia, moderate hypertrichosis, thickening of the skin.

Skeletal system: in the first year of life, growth is within the normal range, then the growth rate decreases, causing short stature. The physique is disproportionate. Mobility in the joints is moderately reduced, dysostoses, keeled chest, kyphoscoliosis, scaphocephaly, macrocephaly are determined.

Respiratory organs: frequent respiratory diseases in the form of rhinitis, otitis, hypertrophy of the palatine tonsils. Perhaps the development of airway obstruction, stenosis of the larynx.

Organs of vision: clouding of the cornea.

Central nervous system: there is a delay in the pace of psychoverbal development, later deep dementia appears. Carpal tunnel syndrome - carpal tunnel syndrome, communicating hydrocephalus. Characterized by the development of pachymeningitis in the cervical region, leading to compression of the spinal cord and subsequent myelopathy.

Cardiovascular system: valvular heart disease.

Gastrointestinal system: hepatosplenomegaly, inguinal-scrotal and umbilical hernias.

As with most recessive diseases, clinical polymorphism is determined by residual enzyme activity and determines the severity of the course and early onset. Depending on the age of onset, certain clinical manifestations may have varying degrees of severity (Appendix D1).

2. Diagnostics

The diagnosis of MPS I is established on the basis of a combination of clinical data, results laboratory research and molecular genetic analysis. The frequency of application of methods for initial evaluation and follow-up is given in Appendix D2.

2.1 Complaints and medical history

• When collecting anamnesis and complaints, it is recommended to pay attention to the following complaints and anamnestic events:

• coarsening of facial features
• frequent respiratory illnesses
• hearing loss
• decreased vision
• recurrent hernias
• clouding of the cornea
• worsening tolerance physical activity, in particular, a decrease in the usual distance traveled
• weakness in the limbs
• stiffness in the joints
• difficulty getting up from a sitting or lying position
• change in gait
• fine motor awkwardness
• delayed psycho-speech development
• violation of the control of the functions of the pelvic organs
• sleep apnea
• stool disorder

2.2 Physical examination

• On examination, attention should be paid to the main physical manifestations of MPSI:

• rough facial features
• short stature,
• joint stiffness,
• mental retardation,
• behavioral disorders
• clouding of the cornea,
• hepatomegaly,
• splenomegaly,
• inguinal-scrotal and umbilical hernias.

The severity of physical manifestations depending on the age of MPS I debut may vary (Appendix D1).

2.3 Laboratory diagnostics

• Recommended Study urinary excretion of dermatan sulfate and heparan sulfate.

Comments: indicators are the main laboratory criteria for type I MPS. Patients with MPS type I have elevated level dermatan sulfate and heparan sulfate in urine.

• Recommended Activity Detection alpha-L-iduronidase in the culture of fibroblasts, isolated leukocytes, or in blood stains dried on filter paper.

Comments: indicators are the main laboratory criteria for type I MPS. In patients with MPS type I, a decrease in activity is determinedalpha-L-iduronidase .

• It is recommended to conduct a molecular genetic study: detection of mutations in the gene IDUA, encoding alpha-L-iduronidase.
• Recommended biochemical analysis blood (determine alanine aminotransferase (ALT), aspartate aminotransferase (AST), total and direct bilirubin, cholesterol, triglycerides, creatine kinase (CPK), lactate dehydrogenase (LDH), calcium, phosphorus, alkaline phosphotase (AP)).
• It is recommended to control the general clinical analysis of blood and urine.

2.4 Instrumental diagnostics

• It is recommended to conduct an ultrasound examination (ultrasound) of organs abdominal cavity, spleen, kidneys.
• A skeletal x-ray is recommended.

Comments:X-ray examination of the skeleton of children with MPS IS reveals the same changes as in Hurler's syndrome, but less pronounced. When radiography hip joints dysplasia of the femoral head. When chest x-ray with MPS I H is determined by the shortening and expansion of the diaphysis of tubular bones. Flattening and expansion of the Turkish saddle, beak-shaped form of the vertebral bodies.

• Electromyography (EMG) is recommended and electroneuromyography (ENMG).

Comments: the study allows you to assess the functional state of muscle tissues, nerves and neuromuscular transmission; Stimulation electroneuromyography (ENMG) can detect median nerve compression even before symptoms appear and should be performed annually starting at age 4-5 years.

• Audiometry recommended.
• It is recommended to conduct a study of the function of external respiration (RF).
• An EEG is recommended

Comments: carry out to control changes in the function of the cerebral cortex and deep brain structures, timely diagnosis epilepsy.

• Polysomnography is recommended.

Comments: to diagnose obstructive sleep apnea, polysomnography is performed, which allows you to determine the nature respiratory disorders(delete central genesis, association with adenoid hypertrophy, heart failure, or a combination of causes).

• Electrocardiography (ECG) and echocardiography (Echo-KG) recommended

Comments: regular ECG, Echo-KG, ECG Holter monitoring, 24-hour monitoring blood pressure necessary for patients with this pathology, since with early age they have cardiovascular disorders.

• Magnetic resonance imaging (MRI) of the brain, internal organs, and skeleton is recommended.

Comments: clinical picture neurological manifestations and the results of objective examination methods do not always correlate. The results of magnetic resonance imaging (MRI) of the brain of patients with MPS are not diagnostically significant for determining cognitive deficits.

Screening for clinical and imaging signs of spinal cord compression. Atlantoaxial joint instability can be seen on a stress-bearing x-ray of the cervical spine, but MRI is required to confirm compression of the spinal cord due to thickening of the meninges.

• Recommended computed tomography (CT) of the brain, internal organs, skeleton.

2.5 Differential Diagnosis

Other types of mucopolysaccharidoses, gangliosidoses, non-infectious polyarthritis.

3. Treatment

The treatment regimen for MPS type I is presented in Appendix D3.

3.1 Conservative treatment

• It is recommended to carry out an enzyme replacement therapy(FZT). ERT is carried out with laronidase g (ATX code A16AB05).

Comments:1 ml of solution contains 100 IU (approximately 0.58 mg) of laronidase. It is a recombinant form of human alpha-L-iduronidase produced using recombinant DNA technology in Chinese hamster cell culture. ERT is designed to restore the level of enzymatic activity sufficient for the hydrolysis of accumulated glycosaminoglycans and to prevent their further accumulation. After administration, laronidase is rapidly eliminated from the systemic circulation and absorbed by cells, entering their lysosomes through mannose-6-phosphate receptors. Recommended dosing regimen: weekly administration at a dose of 100 IU/kg as an IV infusion. The initial infusion rate of 2 U/kg/h can be gradually increased every 15 minutes if well tolerated, up to a maximum of 43 U/kg/h. The entire required volume of the solution should be administered within approximately 3-4 hours. The drug can be used before bone marrow transplantation, immediately after it, and also after transplantation from a heterozygous donor with incomplete displacement of the recipient's cells by donor cells.

• Correction of cardiovascular insufficiency, arterial hypertension is recommended to be carried out by standard methods of conservative treatment adopted in pediatric cardiology.

Comments: according to the indications, the question of the need for surgical correction is resolved.

• Treatment of behavioral disorders is recommended to be carried out with the participation of a neuropsychiatrist; sedatives, tranquilizers, and behavior correctors are usually used.

Comments: the choice of drug, dosage, duration of the course are determined individually. Start taking these drugs under close medical supervision in a round-the-clock / day hospital.

• At symptomatic epilepsy the appointment of anticonvulsants is recommended, however, dosages are recommended to be used less than the average therapeutic ones to reduce the risk of developing possible undesirable effects.

Comments: the selection of an anticonvulsant is carried out by a neuropsychiatrist depending on the type of seizures, localization of the focus of pathological activity.

• In case of ophthalmic disorders, treatment is recommended according to indications, the selection of therapy is carried out on the basis of generally accepted recommendations for the treatment of relevant nosologies.
• Recommended for orthopedic correction of postural disorders, joint stiffness, the use of non-surgical methods: physiotherapy and the use of orthopedic devices in the absence of indications for surgical treatment.
• It is recommended for recurrent otitis media, frequent respiratory diseases of the upper respiratory tract, symptomatic, according to indications - antibiotic therapy in the absence of indications for surgical intervention. With hearing loss - fitting and wearing hearing aids. Obstructive sleep apnea requires oxygen therapy.
• For caries and abscesses, oral hygiene and extraction of teeth, if necessary, are recommended.
• It is recommended to vaccinate patients against pneumococcal, hemophilic infections and other vaccines, the expediency is due to frequent respiratory infections.

3.2 Surgical treatment

• Arthroscopy, surgical hip replacement or knee joint, correction of the axis of the lower limb in the absence of the effect of conservative therapy.
• For communicating hydrocephalus, ventriculo-peritoneal shunting is recommended for patients with type I MPS with progressive ventricular enlargement on MRI and/or confirmed cerebrospinal fluid pressure greater than 25–30 cmH2O (18–22 mmHg).
• Spinal cord compression leads to irreversible neurological disorders therefore, when the first symptoms appear, it is recommended to consider the issue of decompressive surgery before the appearance of pronounced disorders.
• Decompression surgery is recommended for patients with impaired hand function or nerve conduction disorders as determined by electroneuromyography (ENMG) nerve trunks, which results in a rapid, sustained improvement in function. The frequency of recurrence of carpal tunnel syndrome in patients with various types MPS is unknown. Because re-compression of the median nerve due to scarring or glycosaminoglycan deposition is possible, continued monitoring is necessary.
• It is recommended to consider surgical intervention for recurrent otitis media torpid to conservative therapy.

3.3 Bone marrow transplant

• Bone marrow transplantation (BMT) is recommended for patients with MPS 1H before the age of two years with normal or subnormal developmental parameters (DQ>70).

Comments: l Best results have been obtained using bone marrow stem cells from HLA-matched related donors or cord blood stem cells from related donors. TCM leads to a decrease in the size of the liver and spleen, improving the functions of the respiratory and cardiovascular systems. The clouding of the cornea decreases slowly, while not disappearing completely; formed changes in the skeleton, especially the spinal column, are also not stopped in full.

4. Rehabilitation

For a patient with mucopolysaccharidosis type I, a physiotherapist and a physiotherapist develop an individual rehabilitation course, including massage, physiotherapy exercises, physiotherapy procedures (magnetotherapy, thermotherapy, shock wave therapy, biofeedback method and other procedures).

Rehabilitation courses (massage, exercise therapy, physiotherapy, psychological and pedagogical assistance) are preferably carried out in a day hospital with a frequency of 3-4 times a year, the duration is determined by the severity of the condition and the response to the measures taken.

Psychological and pedagogical assistance

It is carried out in a complex of rehabilitation measures. The correctional and pedagogical impact is determined depending on the severity and duration of the course of the disease, the structure of health disorders, the degree of underdevelopment of cognitive activity, the type of emotional response, and the characteristics of the child's behavior. The inclusion of correctional and pedagogical support in the complex of rehabilitation measures provides an additional assessment of the dynamics mental development as one of the important indicators of the state of health, increases the effectiveness of therapeutic interventions, reduces the economic burden of this pathology due to the socialization of patients and the preservation of the psychological potential of able-bodied family members.

Palliative care

It is necessary to provide comprehensive assistance (medical, psychosocial and material) to children with incurable life-limiting diseases. The palliative services include physicians, nurses, psychologists and social workers. Despite the serious condition and the constant need for monitoring, all patients are mostly at home with their family and friends. The main goal of the work of palliative services is to create all necessary conditions to ensure that patients stay at home, and not within the walls of a medical institution, which allows not only to improve the quality of life of patients and their families, but also to significantly reduce government costs for permanent inpatient treatment of such patients.

5. Prevention and follow-up

5.1 Prevention

Prevention of mucopolysaccharidoses - prenatal diagnosis based on the direct determination of enzyme deficiency in amniotic cells.

5.2. Monitoring the condition of children with MPS

The disease has a multisystem nature and irreversible, progressive clinical manifestations, which necessitates observation not only by narrow specialists (otolaryngologists, orthopedic surgeons, ophthalmologists, cardiologists, pulmonologists, neuropathologists, dentists), but also by physiotherapists, speech therapists, psychologists and palliative care workers.

Patients with this nosology should be constantly monitored; 1 time in 6-12 months. (according to the severity of the condition) a comprehensive examination in multidisciplinary hospitals is indicated. The duration of stay in the hospital / day hospital is 21-28 days.

Observation of patients at the place of residence (in an outpatient setting) should be carried out constantly. Laboratory and instrumental examinations and the recommended frequency of their implementation is presented in Appendix D2.

Follow-up of patients with MPS I includes the identification of complications of the underlying disease and concomitant conditions.

6. Additional information affecting the course and outcome of the disease

6.1 Features of anesthesia

When performing general anesthesia, it is necessary to remember the high risk of spinal cord compression due to instability of the atlantoaxial joint. Short neck, limited mobility mandible, an increase in the tongue, pronounced hypertrophy of the adenoids and tonsils create problems during anesthesia, so preference should be given to local or regional anesthesia. The patient is preliminarily consulted by a cardiologist, otorhinolaryngologist, anesthesiologist, neuropathologist. It is mandatory to conduct a complete cardiological examination, polysomnography (to identify the degree of respiratory disorders), if necessary, endoscopy of the nasopharynx and computed tomography of the lungs. Surgery with anesthesia should be performed in large medical centers in ICU, as intubation and subsequent extubation may be difficult in these patients.

6.2 Outcomes and prognosis

Mucopolysaccharidosis I H - severe form

The average life expectancy of patients is approximately 10 years. Respiratory and heart failure, obstructive processes of the upper respiratory tract and infections exacerbate the prognosis.

Mucopolysaccharidosis type I S - mild form

Life expectancy may not be changed and is determined by the phenotypic manifestations of the pathological process.

Mucopolysaccharidosis type I H/S - intermediate form

The rate of progression of the disease is intermediate between the Hurler and Scheye syndromes.

Criteria for assessing the quality of medical care

Table 1- Organizational and technical conditions for the provision medical care.

table 2- Criteria for the quality of medical care.

Bibliography

1. Muenzer J, Wraith J.E., Clarke L.A. Mucopolysaccharidosis I: management and treatment guidelines. Pediatrics. 2009; 123(1):19-29;
2. Martins AM, Dualibi AP, Norato D et al. Guidelines for the Management of Mucopolysaccharidosis Type I. J Pediatr. 2009 ; 155(4);(2):32-46;
3. Thomas JA, Beck M, Clarke JTR, Cox GF Childhood onset of Scheie syndrome, the attenuated form of mucopolysaccharidosis I. J Inherit Metab Dis (2010) 33:421–427.

Annex A1. Composition of the working group

Baranov A.A. Academician of the Russian Academy of Sciences, Professor, Doctor of Medical Sciences, Chairman of the Executive Committee of the Union of Pediatricians of Russia. Awards: Order of the Red Banner of Labor, Order of Honor, Order of Merit for the Fatherland, 4th class, Order of Merit for the Fatherland, 3rd class

Namazova-Baranova L.S. Academician of the Russian Academy of Sciences, Professor, Doctor of Medical Sciences, Deputy Chairman of the Executive Committee of the Union of Pediatricians of Russia..

Kutsev S.I., corresponding member. RAS, MD

Kuzenkova L.M., professor, MD, member of the Union of Pediatricians of Russia

Gevorkyan A.K., candidate of medical sciences, member of the Union of Pediatricians of Russia

Vashakmadze N.D., candidate of medical sciences, member of the Union of Pediatricians of Russia

Savostyanov K.V., Ph.D., member of the Union of Pediatricians of Russia

Pushkov A.A., Ph.D., member of the Union of Pediatricians of Russia

Zakharova E.Yu., MD

Podkletnova T.V., candidate of medical sciences, member of the Union of Pediatricians of Russia

Vishneva E.A., candidate of medical sciences, member of the Union of Pediatricians of Russia

1. Pediatric cardiologists;
2. Pulmonologists;
3. pediatricians;
4. General practitioners (family doctors);
5. Physicians - geneticists;
6. Endoscopists;
7. Doctors - radiologists;
8. Doctors of functional diagnostics;
9. Pediatric dentists
10. Pediatric surgeons
11. Doctors pediatric anesthesiologists-resuscitators;
12. Pediatric neurologists;
13. Medical students
14. Students in residency and internship

Clinical guidelines are based on a systematic review of the literature 1992-2013. Medline (Pubmed version), Embase (Dialog version) and Cochrane Library databases, using generated protocols (Mucopolysaccharidosis I: management and treatment guidelines. Muenzer J, Wraith JE, Clarke LA; Pediatrics. 2009 Jan;123(1):19- 29; Guidelines for the Management of Mucopolysaccharidosis Type I. Martins AM, Dualibi AP, Norato D et al. J Pediatr. Vol. 155, No. 4, Suppl. 2. October 2009), current international clinical guidelines for the diagnosis, treatment and management of patients with metabolic diseases.

Mucopolysaccharidoses are rare hereditary diseases, which excludes the possibility of conducting large cohort and randomized controlled trials, and only expert case studies published in the last two decades are used to create protocols for diagnosis and therapy.

Annex A3. Related Documents

Orders for the provision of medical care:

1. Order of the Ministry of Health and social development Russian Federation of April 16, 2012 N 366n "On approval of the procedure for the provision of pediatric care")
2. Order of the Ministry of Health of the Russian Federation "On approval of the procedure for providing medical care to patients with congenital and (or) hereditary diseases" dated November 15, 2012 N 917n).

Medical care standards:

1. Order of the Ministry of Health of Russia dated November 9, 2012 N 791n "On approval of the Standard for specialized medical care for children with mucopolysaccharidosis type II"

1. Order of the Ministry of Health of Russia dated 09.11.2012 N 790n "On approval of the Standard for specialized medical care for children with mucopolysaccharidosis types III, IV and VII."
2. Order of the Ministry of Health of Russia dated November 9, 2012 N 834n "On approval of the Standard for specialized medical care for children with mucopolysaccharidosis type VI"

Appendix B. Patient Management Algorithms

Appendix B. Information for Patients

The reactions of parents and relatives to the diagnosis of Mucopolysaccharidosis vary.

At first, this can be a relief, especially if the parents feel that their child is not doing well, and rush from doctor to doctor, trying to find out what is wrong. It is clear that no one wants a diagnosis of Mucopolysaccharidosis, but at the very first moment, parents can calm down a little - after all, their child has been diagnosed, and if so, it is clear in which direction it will be necessary to go further. However, very soon comes the understanding that not everything is so simple. That there is no such treatment that would heal the child immediately. Most parents experience overwhelming feelings of devastation and then go through all the stages of sadness.

Going through this difficult period, it is very important to have hope. It is very important to communicate with families in which there are similar problems, to study information about the disease and its accompanying aspects. Remember that medicine does not stand still, new and existing methods of treatment are being developed, which leads to an improvement in the quality of life. Remember that you are not alone.

Signs of Mucopolysaccharidosis vary widely from patient to patient. Patients with problems with the heart, lungs, digestive system, musculoskeletal system and brain lesions, many with Mucopolysaccharidosis experience more pain than ordinary people.

AT early childhood children with severe mucopolysaccharidosis may be hyperactive, strong, usually cheerful, but very easily fatigued. They have an underestimated degree of concentration of attention, their intellectual age is below the age of physical development. Such a child may, for example, lock the bathroom door, but is unable to figure out how to get out, even when the adult explains it many times. They love rough destructive games, making noise and throwing toys for such children is more like a game. They can be unaware of the dangers, stubborn and undisciplined, because they often simply cannot understand what is required of them. Some children may have violent outbursts. Some may use the toilet for a while, but most use diapers. It is problematic for parents of such children to simply sleep. They should not be embarrassed to ask the doctor for advice on the child's disinhibition and correcting his behavior.

Children with a mild form of mucopolysaccharidosis, as a rule, do not completely differ in behavior from healthy children. At times, they can be unrestrained from frustration when their physical limitations make life difficult. It is necessary to encourage manifestations of their independence in every possible way.

The teenage years can be especially difficult for these children. They just need help, understanding, encouragement, a good and kind word.

Appendix D

Annex G1. The severity of clinical manifestations depending on the age of onset of MPS1

Annex D2. Management of children with type I MPS

1 - For children over 3 years old; distance traveled in 6 minutes (preferably the same amount of time as in the previous tests of this patient); number of stairs climbed in 3 minutes. SpO2 saturation indicators, respiratory rate, heart rate before and after exercise are estimated.

2- DQ or Intelligence Quotient (IQ) is a way of comparing age-specific intelligence (a child's intelligence relative to his peers) with chronological age (a child's actual age).

IQ is calculated by dividing intellectual age by chronological age and multiplying by 100 to get a whole number. The average IQ for any age is considered to be 100.

Annex G3. Treatment regimen for MPS type I

Annex G4. Algorithm for diagnosing MPS type I

Annex D5. Explanation of notes

… and - a medicinal product included in the List of Essential and Essential Medicines for medical use for 2016 (Decree of the Government of the Russian Federation of December 26, 2015 N 2724-r)

… VC - medicinal product included in the List of medicinal products for medical use, including medicinal products for medical use prescribed by decision medical commissions medical organizations (Decree of the Government of the Russian Federation of December 26, 2015 N 2724-r)

… 7n- a medicinal product included in the List of medicinal products intended to provide patients with hemophilia, cystic fibrosis, pituitary dwarfism, Gaucher's disease, malignant neoplasms lymphoid, hematopoietic and related tissues, multiple sclerosis, persons after organ and (or) tissue transplantation (Decree of the Government of the Russian Federation of December 26, 2015 N 2724-r)