Mucopolysaccharidosis are a group of genetically determined diseases resulting from a violation of the metabolism of acidic mucopolysaccharides (glycosaminoglycans). Systemic skeletal lesions and delayed physical development are characteristic. In some forms, mental retardation is observed. Cardiac disorders, pathology of the visual organs, hernia formation, neurological disorders, hypertrichosis, enlargement of the liver and spleen are possible. The diagnosis is made on the basis of clinical signs, radiography data and other studies. Treatment is symptomatic.
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Mucopolysaccharidosis are a group of genetic diseases accompanied by the accumulation of acidic mucopolysaccharides in organs and tissues. The cause of development is the inherited inferiority of lysosomal enzymes. Disease was first described by Gurler in 1917. Treatment is carried out by orthopedic traumatologists with the participation of cardiologists, ophthalmologists, neurologists, otolaryngologists and other specialists.
Mucopolysaccharidosis type IH
Mucopolysaccharidosis type IH or Gurler syndrome occurs in 1 newborn out of 20-25 thousand. Symptoms of mucopolysaccharidosis appear during the first year of life, a complete clinical picture is formed by 1-2 years. This form of mucopolysaccharidosis is characterized by rough facial features and deformity of the skull in the form of a boat keel (scarocephaly). Due to enlarged adenoids and malformations in the face and nose, patients breathe through their mouth. Progressive deformities of the limbs and other parts of the skeleton, lag in growth are noted.
The spine of patients with mucopolysaccharidosis is curved, which causes a “cat’s back” symptom in the sitting position. There is a shortening of the neck, a high location of the shoulder blades and the standing of the lower ribs. The hands are wide, resembling a clawed paw. Over time, joint contractures form in patients with this disease. First, the elbow and shoulder joints are affected, then the knee, hip and ankle joints. Due to the limitation of movements, a characteristic gait arises – on tiptoe with half–bent legs.
The tones of the heart are muted, the boundaries are expanded. During auscultation, systolic noises are detected, diffuse myocardial lesion is detected on the ECG. The anterior abdominal wall of patients with mucopolysaccharidosis is weakened, the abdomen is enlarged, hydrocele, umbilical and inguinal hernias are often detected. The liver and spleen are enlarged. Visual and hearing impairments are characteristic. Possible opacification and enlargement of the cornea, retinal pigmented dystrophy, glaucoma, optic nerve atrophy and congestion in the fundus. Patients with mucopolysaccharidosis of this type develop progressive mental retardation. Movement coordination disorders, paresis and paralysis may occur. Excessive growth of fluffy hair is revealed.
Spine x-ray of patients indicates a characteristic deformation of the vertebrae. The vertebrae have a cuboid shape, their contours are rounded, in the transitional part there is a beveling of the anteropteric corners, angular kyphosis, thickening and shortening of the processes. Chest x-ray determines the thickening of the anterior and thinning of the posterior parts of the ribs, accompanied by their scapular or sabre-shaped deformation, shortening and deformation of the collarbones, reduction and displacement of the heads of the humerus bones.
Radiography of the pelvis confirms the narrowing of the pelvic ring, the obliquity of the acetabulum and the reduction of the femoral heads. Radiographs of tubular bones reveal thinning of the cortical layer and expansion of the medullary canal. Radiography of the bones of the hand indicates underdevelopment of the nail phalanges, shortening and expansion of the metacarpal bones, proximal and middle phalanges. On X-rays of the skull, underdevelopment of the bones of the facial skull, craniostenosis and macrocephaly are determined.
Mucopolysaccharidosis type I-S
Mucopolysaccharidosis type I-S or Sheye’s disease (described in 1962 by the American ophthalmologist Sheye) is a later, relatively favorably occurring variant of mucopolysaccharidosis type IH (Gurler syndrome). Up to 3-6 years of age, the development of children corresponds to the norm. The first sign of mucopolysaccharidosis is flexion contractures of the fingers. Subsequently, extension in the wrist, elbow and shoulder joints is limited. Contractures of the lower extremities, as a rule, are weakly expressed. The complete clinical picture of mucopolysaccharidosis is formed by the beginning of adolescence.
Patients with mucopolysaccharidosis are stocky, short, with rough facial features and well-developed muscles. There is increased hair loss (hypertrichosis). Inguinal or umbilical hernias often occur. The skin on the fingers is stretched and thickened. Due to compression of the median nerve, carpal tunnel syndrome may develop, accompanied by atrophy of the muscles of the tenar region and paresthesia in the area of the III-IV fingers. In some patients with mucopolysaccharidosis, aortic stenosis, aortic valve insufficiency, retinal pigmented dystrophy, glaucoma and corneal opacity are detected. Intelligence is normal, enlargement of the spleen and liver is uncharacteristic. Radiographs show a pattern similar to mucopolysaccharidosis type IH, but the pathological changes are less pronounced.
Mucopolysaccharidosis type II
Mucopolysaccharidosis type II or Hunter syndrome is more often detected in boys and usually develops at 2-3 years of age. As with disease type IH, there is scaphocephaly, coarsening of facial features, low voice and difficulty breathing due to deformation of the facial skeleton. At the same time, kyphosis characteristic of mucopolysaccharidosis type IH is usually not detected, the symptom of “cat’s back” is negative. Patients often suffer from respiratory infections (bronchitis, tracheitis, pneumonia). Gradually, movement coordination disorders develop, aggressiveness increases. The mood is unstable, with sharp fluctuations.
Also, with this form of mucopolysaccharidosis, there is a slight increase in the spleen and liver, progressive hearing loss, nodules on the skin of the back and some decrease in intelligence. Subsequently, corneal opacity may develop. The X–ray picture is similar to that of type I-S mucopolysaccharidosis. There are two possible variants of the disease development: favorable (option B) and unfavorable (option A). With a favorable variant, the symptoms are not clearly expressed, sometimes there is a slight mental retardation, patients with mucopolysaccharidosis can live up to 30 years or more. The unfavorable variant is characterized by a vivid clinical picture and serious intellectual disabilities. The fatal outcome occurs in adolescence.
Mucopolysaccharidosis type III
Mucopolysaccharidosis type III or Sanfilippo disease (described in 1963 by the American pediatrician Sanfilippo) develops in 1 newborn out of 100-200 thousand. In the first years of life, development corresponds to age, sometimes there are difficulties swallowing and awkward gait. At the age of 3-5 years, a child becomes apathetic and begins to lag behind in development. There are speech disorders, coarsening of facial features, urinary and fecal incontinence. Over time, mental retardation progresses and occupies a central position in the clinical picture of this type of mucopolysaccharidosis.
Along with intellectual disabilities, there is a moderate increase in the liver and spleen, increased hair loss, contractures and growth retardation. Pathology from the eyes and the cardiovascular system is unusual for this form of mucopolysaccharidosis. The X–ray picture is unchanged or as in mucopolysaccharidosis type I-S, but less pronounced. Patients with mucopolysaccharidosis of the third type, as a rule, die at the age of 10-20 years from infectious complications.
Mucopolysaccharidosis type IV
Mucopolysaccharidosis type IV or Morchio’s disease (described in 1929 by the Uruguayan pediatrician Morchio) is observed in 1 newborn out of 40 thousand. Up to 1-3 years old, children develop normally. Subsequently, there is a significant lag in growth, shortening of the neck and trunk, contractures and valgus deformity of the limbs, scoliosis or kyphosis, various deformities of the chest, decreased muscle strength, thickening of the skin and coarsening of facial features. With this type of mucopolysaccharidosis, inguinal and umbilical hernias, corneal dystrophy and hearing loss often develop. Intelligence is preserved.
On radiographs of the spine, kyphosis, scoliosis, expansion and flattening of the vertebral bodies are determined. Radiography of the pelvis and extremities reveals multiple deformities, uneven contours, flattening of the femoral heads, shortening of the forearm bones and deformities of the feet. The average life expectancy of patients with mucopolysaccharidosis is less than 20 years. Death in this form of mucopolysaccharidosis occurs due to concomitant diseases complicated by cardiopulmonary insufficiency.
Other types of mucopolysaccharidosis
Mucopolysaccharidosis type VI or Maroto-Lamy disease (described in 1960 by the French Lamy and Maroto) develops at the age of 2 years and older. There is a coarsening of facial features, stunting, shortening of the neck, joint contractures and barrel-shaped deformation of the chest. Frequent colds are characteristic. Hernias, enlargement of the liver and spleen are possible. The intellect does not suffer. There are two variants of the course: classical and mucopolysaccharidosis with mild clinical manifestations. On radiographs of patients with mucopolysaccharidosis, cuboid or wedge-shaped deformation of the vertebrae, triangular deformation of the pelvis, underdevelopment and deformation of the femoral heads, shortening of the fibula are determined.
Type VII mucopolysaccharidosis proceeds like type III mucopolysaccharidosis, differences are revealed only during biochemical studies. Type VIII mucopolysaccharidosis resembles type IV mucopolysaccharidosis in symptoms, but, unlike it, is accompanied by mental retardation.
The diagnosis of mucopolysaccharidosis is established on the basis of a characteristic clinical and radiological picture, the detection of glycosaminoglycans in urine, the study of enzyme activity in cell cultures, genetic sequencing. During the examination, patients are consulted by various specialists: cardiologist, gastroenterologist, ophthalmologist, otolaryngologist, neurologist, psychiatrist, etc., instrumental studies are conducted to assess the condition of various organs and systems.
Pathogenetic therapy has not been developed. Treatment is symptomatic, can be both conservative and operative. Prevention and treatment of respiratory infections is carried out, correction of visual and hearing impairments is carried out. If necessary, hernia repair and hernioplasty, operations to eliminate contractures and correct skeletal deformities are performed.
Prognosis and prevention
The prognosis for all types of mucopolysaccharidosis is unfavorable – the continued accumulation of metabolic products in tissues leads to an aggravation of pathological changes on the part of all organs and systems. The use of any therapeutic agents (blood transfusions, hormone administration, etc.) in mucopolysaccharidosis provides only a temporary improvement. Prenatal prophylaxis is recommended.
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