What Is Maroteaux Lamy Syndrome?

Mucopolysaccharidosis (MPS) is a group of congenital genetic diseases. Due to the lack of mucopolysaccharide degrading enzymes, acidic mucopolysaccharides cannot be completely degraded, causing mucopolysaccharides to accumulate in different tissues of the body, causing a series of clinical problems such as skeletal deformity and mental retardation. Symptoms and signs.

Basic Information

Visiting department

Pediatrics

Multiple groups

Children

Common causes

Autosomal recessive or sex-linked recessive inheritance, caused by disorders of acidic mucopolysaccharide metabolism

Common symptoms

Short stature and special face, indifferent expression, large head, ugly face, small cracked eyes, wide eye distance, low equal bridge of nose

Causes of mucopolysaccharidosis in children

This symptom is an autosomal recessive or sex-linked recessive inheritance, which is related to the disorder of acidic mucopolysaccharide metabolism. IH type, IS type, and IH / S type patients have lysosomal -levuduronidase deficiency, In addition, the decomposition of mucopolysaccharides is impeded. Incompletely degraded mucopolysaccharides are deposited in the cells of various tissues in the body and excreted from the urine. This abnormal deposition involves a variety of organs and tissues, such as the heart, brain, liver, and spleen. In heart valves, blood vessels, meninges, cornea, periosteum and other tissues, Hurler cells with mucopolysaccharide deposition can be seen, which is the pathological basis for various clinical manifestations.

Clinical manifestations of mucopolysaccharidosis in children

Mucopolysaccharide is the main component of connective tissue, so the abnormal metabolism of mucopolysaccharide affects the whole body organs. At present, the enzyme defects that cause mucopolysaccharidosis have been identified, and they are divided into 6 types. Patients are usually normal at birth, and clinical symptoms gradually become apparent with increasing age. The common feature is that they have growth retardation around one year after birth. With the exception of type IV and type VI, patients are accompanied by mental retardation. Different types of diseases have different clinical characteristics, which need to be identified in the diagnosis. The main manifestations are short stature and special face, indifferent expression, large head, ugly face, small eye splits, wide eye distance, and flat nose. , Large nostrils, thick lips, prominent forehead and double palate, more hair but lower hairline, short neck, most of the corneal opacities. Progressive joint distortion, thoracic deformity, kyphosis or scoliosis, knee valgus, claw-shaped hands, early onset of liver, splenomegaly, deafness, enlarged heart, etc. The following are the clinical characteristics of each type:

1. Mucopolysaccharidosis -H (Hurler syndrome)

This type is the most serious type, often dying around the age of 10, clinically visible low intelligence, ugly face, hepatosplenomegaly, skeletal disease, cardiovascular disease, corneal opacity and deafness. Peripheral blood leukocytes and lymphocytes can see deep-stained granules with different sizes and different morphology, sometimes in the form of vacuoles, and a large amount of acidic mucopolysaccharide is excreted in the urine (> 100mg / d, normally 3-25mg / d).

2. Mucopolysaccharidosis type II (Hunter syndrome)

It is clinically heavy, similar to mucopolysaccharid -H type, onset at the age of 2 to 6 years, with special face and skeletal deformities, but no spine-shaped deformities and no corneal opacities in the spine. The patient is mentally backward, has progressive deafness, can develop congestive heart failure, and hepatosplenomegaly.

3. Mucopolysaccharidosis type III (Sanfilippo syndrome)

Clinically, it can be divided into 4 subtypes, which are caused by 4 different enzyme defects. Type IIIA is deficient in heparan sulfate sulfatase, type IIIB is deficient in N-acetyl--D-aminoglucosidase, type IIIC is acetyl-CoA: deficiency of -aminoglucoside-N-acetyltransferase, type IIID Deficiency for N-acetylglucosamine-6-sulfatase. It can be seen clinically that the child develops normally within the age of 1 year, and gradually develops language and behavioral obstacles. The growth and development lags behind. The degenerative pathological changes of the nervous system in childhood are more obvious, including hepatosplenomegaly, hernia, ugly face, joint stiffness which performed.

4. Mucopolysaccharidosis Type IV (Morquio Syndrome)

The clinical features are similar to those of mucopolysaccharidosis type -H, but without mental retardation. There are obvious growth obstacles, skeletal deformities, X-rays show typical mucopolysaccharidosis, spine with beak-like changes, flat vertebrae, ribbon ribs, chicken breasts, etc., ugly face, short nose, large mouth, poor dental development, cornea turbid. Adolescent development can be normal, with symptoms of spinal cord compression with age, compression paraplegia and respiratory paralysis occur at later stages.

5. Mucopolysaccharidosis type (Maroteaux-Lamy syndrome)

The clinical manifestations are similar to those of mucopolysaccharidosis -H, but there is no mental retardation. A large amount of dermatan sulfate is excreted in the urine. The pathogenic gene is N-acetylgalactosamine-4-sulfatase. The gene is located on chromosome 5q11-5q13, which is an autosomal recessive genetic disease.

6. Mucopolysaccharidosis

The clinical manifestations are the same as those of mucopolysaccharidosis type -H, but the individual's severity varies and the variation is large. This type is an autosomal recessive inherited disease. Due to the lack of -glucuronidase, 4/6 chondroitin sulfate is deposited in the body. The gene is located on chromosome 7q21.11 and has 12 exons.

Mucopolysaccharidosis in children

1. Determination of mucopolysaccharides in urine

A qualitative test is usually performed with the toluidine blue method, and the patient's urine is positive.

2. Acetate thin film electrophoresis

Can distinguish the type of mucopolysaccharide excreted in urine and type.

3. Enzymatic analysis

According to the determination of specific enzyme activities in leukocytes and fibroblasts, as well as the type of mucopolysaccharide excreted in urine, mucopolysaccharidosis can be typed.

4. Hematology examination

Peripheral blood leukocytes, lymphocytes, and bone marrow blood cells can be seen with deep stained granules of different sizes and different shapes, sometimes in the form of vacuoles, called Reilly granules, which have been confirmed as mucopolysaccharide.

5. X-ray examination of bones

Poor bone, thin cortex, enlarged skull, enlarged saddle, kyphosis or scoliosis, vertebral body wedge-shaped or flat, chest and lumbar vertebral body with anterior lower inferior lip-like protrusion or bird's beak The ribs are small at the spine end and wide at the sternum end. They are ribbon-like, with short and thick metacarpals, pointed bases, narrow rounded distal fingers, and delayed mature ossification center of the carpal bone.

6.B-ultrasound

Swelling of the liver, spleen, and heart can be found, and myocardial function declines.

7. Electric audiometry

Hearing drops.

8. EEG

Visible abnormal brain waves.

9. Intelligence test

Intellectual decline.

Diagnosis of mucopolysaccharidosis in children

Diagnosis can be made based on clinical features, special faces and signs, X-ray findings, and urinary mucopolysaccharidemia. The family history of mucopolysaccharidic patients is helpful for early diagnosis. The diagnosis depends on the detection of related genes.

Differential diagnosis of mucopolysaccharidosis in children

The clinical diagnosis of various types of mucopolysaccharidosis is based on clinical manifestations, which are mainly X-ray multiple skeletal dysplasia and different mucopolysaccharides excreted in the urine. Considering this disease, the diagnosis must be tested for the lack of relevant enzymes. In addition, the disease should be distinguished from rickets, multiple sulfatase deficiency, congenital hypothyroidism, mannose disease, aspartate glucosamineuria, and systemic ganglioside deposition. The clinical manifestations of these diseases are similar to those of mucopolysaccharidosis, but the mucopolysaccharide output in urine does not increase.

Complications of mucopolysaccharidosis in children

Lack of growth, mental retardation, and various progressive bone distortions affect motor function, liver and spleen enlargement, deafness, language and behavioral disorders, compression paraplegia and respiratory paralysis in the later stages, and congestive heart failure.

Treatment of mucopolysaccharidosis in children

Mucopolysaccharidosis is a chronic and progressive disease. Currently, there is no drug treatment method. Special treatment is expensive and can be treated symptomatically.

Bone marrow transplant

To replace the lack of various types of enzymes in mucopolysaccharidosis. Mucopolysaccharidosis -H patients have improved their intelligence after bone marrow transplantation. The mucopolysaccharides in peripheral tissues disappear, the cornea is clear, the liver and spleen shrink, and the mucopolysaccharides in the urine are normal. Early diagnosis and bone marrow transplantation may reduce bone damage. Bone marrow transplantation has been confirmed. Mucopolysaccharidosis , , and are definitely effective. Because , , and are often accompanied by severe mental retardation or skeletal deformity, the treatment may be unsatisfactory when clinical symptoms appear. Transplantation for other types of mucopolysaccharidosis is still being tested.

At present, all types of mucopolysaccharidosis are considered to have indications for hematopoietic stem cell transplantation, and it is generally believed that the effect is good before two years of age. Gene therapy is for further study.

2. Enzyme replacement therapy

It is simple and low risk, but requires life-long treatment and high cost. There is no drug supply in China. In addition, enzyme preparations cannot reach the central nervous system and have limited effects in improving neurological symptoms or preventing further damage to the nervous system.

Prognosis of mucopolysaccharidosis in children

With the increase of age, the condition worsens, progressive mental retardation occurs, and bone and joint symptoms worsen. Most children die of pneumonia or heart disease in childhood, and a few can survive to adults.

Prevention of mucopolysaccharidosis in children

Mucopolysaccharidosis is caused by a congenital defect of lysosomal acid hydrolase. There is no effective preventive measure except to comply with the provisions of the Marriage Law, to avoid marriage between close relatives, and to reduce the incidence of genetic diseases in offspring. There are siblings who are not sick in the family and should be checked regularly to make an early diagnosis. If you need to have a second child, genetic counseling should be carried out, and prenatal diagnosis can be made if possible.

Most types of mucopolysaccharidosis can be analyzed by cDNA analysis of amniotic fluid cells for prenatal diagnosis and termination of pregnancy if necessary.