Mucopolysaccharidosis type IV

Mucopolysaccharidosis type IV (synonyms: galactose-6-sulfatase deficiency, beta-galactosidase deficiency, Morquio syndrome, mucopolysaccharidosis IVA, mucopolysaccharidosis IVB).

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Epidemiology

The disease occurs worldwide, with an average incidence in the population of 1 in 40,000 live births.

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Causes mucopolysaccharidosis type IV.

Mucopolysaccharidosis IV is an autosomal recessive progressive genetically heterogeneous disease resulting from mutations in the genes encoding galactose-6-sulfatase (N-acetylgalactosamine-6-sulfatase), which is involved in the metabolism of keratan sulfate and chondroitin sulfate, or in the beta-galactosidase gene (this form is an allelic variant of Gml gangliosidosis), leading to the manifestation of mucopolysaccharidosis IVA and mucopolysaccharidosis IVB, respectively. The N-acetyl-galactosamine-6-sulfatase gene (GALNS) is located on the long arm of chromosome 16 - 16q24.3. Among 148 known mutations, missense mutations account for 78.4%, nonsense mutations - 5%, small deletions - 9.2%, large deletions and insertions - 4%. 26.4% of mutations were found in dinucleotides. The beta-galactosidase gene - GBS - is located on the short arm of chromosome 3 - Зр21.

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Symptoms mucopolysaccharidosis type IV.

Both subtypes of Morquio syndrome are characterized by growth retardation, corneal opacity, skeletal abnormalities (kyphoscoliosis, pectus carinatum, hip subluxations), aortic valve insufficiency, and normal intelligence.

Mucopolysaccharidosis IVA is usually more severe than mucopolysaccharidosis IVB. Hallux valgus, kyphosis, growth retardation with shortening of the trunk and neck, and gait disturbances are the first symptoms characteristic of Morquio syndrome. Other common disorders associated with this disease include mild corneal opacity, glaucoma, small teeth with enamel defects, multiple caries, hepatomegaly, and acquired heart defects primarily affecting the aortic valve. Odontoid hypoplasia combined with ligamentous weakness may lead to atlantoaxial subluxation and myelopathy of the cervical spine.

Forms

There are two known subtypes of mucopolysaccharidosis type IV: mucopolysaccharidosis IVA and mucopolysaccharidosis IVB, which differ in the primary biochemical defect.

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Diagnostics mucopolysaccharidosis type IV.

To confirm the diagnosis of mucopolysaccharidosis IV, the level of urinary glycosaminoglycans excretion and the activity of lysosomal N-acetyl-galactosamine-6-sulfatase and beta-galactosidase are determined. In the case of mucopolysaccharidosis IV, as a rule, the total excretion of glycosaminoglycans in the urine increases and hyperexcretion of keratan sulfate is observed. However, cases without hyperexcretion of keratan sulfate are known. Enzyme activity is measured in leukocytes or skin fibroblast culture using an artificial fluorogenic substrate.

Prenatal diagnostics is possible by measuring enzyme 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.

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Differential diagnosis

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

Treatment mucopolysaccharidosis type IV.

No effective methods have been developed. Symptomatic therapy is being performed. A drug for enzyme replacement therapy is being developed and is undergoing stage II clinical trials.