Mucopolysaccharidosis type VI: causes, symptoms, diagnosis, treatment

Mucopolysaccharidosis type VI (synonyms: lysosomal M-acetylgalactosamine-4-sulfatase deficiency, arylsulfate B deficiency, Maroteaux-Lamy syndrome).

Mucopolysaccharidosis type VI is an autosomal recessive disorder characterized by severe or mild clinical symptoms; it is similar to Hurler syndrome but differs from it in that intelligence is preserved.

ICD-10 code

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

Epidemiology

The disease occurs worldwide, with an average incidence in the population of 1 in 320,000 live births.

Causes and pathogenesis of mucopolysaccharidosis type VI

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

A previously undescribed mutation, R152W (27.8%), is relatively common among Russian patients.

Symptoms of mucopolysaccharidosis type VI

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

In patients with severe Maroteaux-Lamy syndrome, the first symptoms of the disease usually appear at the age of two years and become evident by the age of 6-8 years. The main symptoms are corneal opacity, features of gargoyleism, short neck, macrocephaly, half-open mouth, stiffness of large and small joints, acquired heart defects, communicating hydrocephalus and symptoms of multiple dysostosis. Mild and intermediate forms of Maroteaux-Lamy syndrome are similar to Scheie syndrome. The most common symptom in this disease is myelopathy of the cervical spine as a result of odontoid hypoplasia. Most patients have mild chest deformity and claw-like deformity of the hands. Hepatosplenomegaly is common, isolated splenomegaly is less common. As a rule, the intellect of patients is not affected. In most cases, there is a deterioration in vision and hearing, disturbances in the structure of tooth enamel, cystic expansion of the dental sacs, malocclusion, condylar defects and gingival hyperplasia.

Diagnosis of mucopolysaccharidosis type VI

Laboratory diagnostics

To confirm the diagnosis of mucopolysaccharidosis VI, the level of urinary glycosaminoglycan excretion is determined and arylsulfatase B activity is measured. Total excretion of glycosaminoglycans in urine increases; hyperexcretion of dermatan sulfate is observed. Arylsulfatase B activity is measured in leukocytes or skin fibroblast culture using an artificial chromogenic substrate.

Prenatal diagnosis is possible by measuring arylsulfatase B activity in chorionic villus biopsy at 9-11 weeks of pregnancy and/or determining the spectrum of glycosaminoglycans in amniotic fluid at 20-22 weeks of pregnancy. For families with a known genotype, DNA diagnostics can be performed in early pregnancy.

Differential diagnostics

Differential diagnostics is carried out both within the group of mucopolysaccharidoses and with other lysosomal storage diseases: mucolipidoses, galactosialidosis, sialidosis, mannosidosis, fucosidosis, GM1 gangliosidosis.

Treatment of mucopolysaccharidosis type VI

The drug Naglazyme (Biomarin) is registered in Europe and the USA for the treatment of mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome). Clinical trials have demonstrated improvement in many indicators of this disease.

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