Mucopolysaccharidosis, type VI: causes, symptoms, diagnosis, treatment

Mucopolysaccharidosis, type VI (synonyms: insufficiency of lysosomal M-acetylgalactosamine-4-sulfatase, insufficiency of arylsulfatea B, Maroto-Lamy syndrome).

Mucopolysaccharidosis, type VI is an autosomal recessive disease characterized by severe or mild clinical symptoms; is similar to the Hurler syndrome, but differs from it with a reserved intellect.

ICD-10 code

• E76 Disorders of glycosaminoglycan metabolism.
• E76.2 Other mucopolysaccharidoses.

Epidemiology

The disease is found all over the world, the average frequency of the disease in the population is 1 per 320 000 live births.

The causes and pathogenesis of type VI mucopolysaccharidosis

Mucopolysaccharidosis VI is an autosomal recessive progressive disease caused by mutations in the structural gene of lysosomal N-acetylgalactosamine-4-sulfatase (arylsulphateate B), an enzyme involved in the degradation of dermatan sulfate. The arylsulfate gene B - ARSB - is located on the long arm of the chromosome 5 - 5qll-ql3.

Russian patients have relatively often encountered a mutation not previously described - R152W (27.8%).

Symptoms of mucopolysaccharidosis type VI

There are three clinical forms that differ in the severity of clinical manifestations: severe, mild and intermediate.

Usually, in patients with severe form of Maroto-Lamy syndrome, the first symptoms appear at the age of two and become evident by the 6th to 8th year of life. The main symptoms are corneal opacity, features of gargoilism, short neck, macrocephaly, half-open mouth, stiffness of large and small joints, acquired heart defects, communicating hydrocephalus and symptoms of multiple dysostosis. The light and intermediate forms of the Maroti-Lamy syndrome are similar to the Scheye syndrome. The most frequent symptom in this disease is myelopathy of the cervical spine as a result of odontoid hypoplasia. The majority of patients observe mild chest deformity and deformity of the wrists as a "clawed paw". Frequent hepatosplenomegaly occurs, rarely - isolated splenomegaly. As a rule, the intellect in patients does not suffer. In most cases, loss of vision and hearing, impaired tooth enamel structure, cystoid dilation of the dental sacs, bite anomaly, condylar defects and gingival hyperplasia are noted.

Diagnosis of mucopolysaccharidosis type VI

Laboratory diagnostics

To confirm the diagnosis of mucopolysaccharidosis VI, the level of excretion of urinary glycosaminoglycans is measured and the activity of arylsulfatase B is measured. The total excretion of glycosaminoglycans in the urine increases; observe the hyperexcretion of dermatan sulfate. The activity of arylsulfatase B is measured in leukocytes or a culture of skin fibroblasts using an artificial chromogenic substrate.

Prenatal diagnosis is possible by measuring the activity of arylsulfatase B in a chorionic villus sampling at the 9-11th week of pregnancy and / or by determining the spectrum of glycosaminoglycans in the amniotic fluid at the 20-22nd week of pregnancy. For families with a known genotype, it is possible to carry out DNA diagnostics in the early stages of pregnancy.

Differential diagnostics

Differential diagnosis is carried out both within the group of mucopolysaccharidosis, and with other lysosomal accumulation diseases: mucolipidosis. Galactosialidosis, sialidosis, mannosidosis, fucosidosis. GM1-gangliosidose.

Treatment of mucopolysaccharidosis type VI

The drug jellyfish (Naglazyme, Biomarin) is registered in European and US countries for the treatment of mucopolysaccharidosis, type VI (Maroto-Lamy syndrome). Clinical trials have demonstrated the improvement of many indicators in this disease.

[1], [2], [3]