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

Mucopolysaccharidosis, type VII (synonyms: Sloi syndrome, insufficiency of lysosomal beta-D-glucuronidase).

ICD-10 code

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

Epidemiology

Mucopolysaccharidosis, type VII is an extremely rare disease, in the literature there are descriptions of several dozen patients.

Causes and pathogenesis of type VII mucopolysaccharidosis

Mucopolysaccharidosis VII is an autosomal recessive progressive disease resulting from a decrease in the activity of lysosomal beta-D-glucuronidase, which is involved in the metabolism of dermatan sulfate, heparan sulfate, and chondroitin sulfate. The beta-glucuronidase gene - GUSB - is located on the long arm of the chromosome 7 - 7q21.ll. 77.8% of the mutations in the gene are dotted. In Russia, no patient with MPS VII was diagnosed.

Symptoms of mucopolysaccharidosis type VII

Most of the severe forms of this syndrome manifest from birth as a so-called fatal non-immune fetal edema and can be detected in utero when performing ultrasound. In other patients, the main clinical symptoms appear from birth in the form of hepatosplenomegaly, signs of multiple dysostosis and compaction of the skin. In less severe cases of illness, debut symptoms occur in the first year of life and are similar to those in the Hurler syndrome or severe form of Hunter syndrome. Since birth, patients have umbilical or inguinal hernia, patients often get respiratory viral infections and otitis. Gradually formed rough features of the type of gargoyilism, skeletal disorders and there is hepatosplenomegaly and opacity of the cornea. Often noted growth retardation, deformation of the chest by the type of keel and kyphosis of the spine.

As the disease progresses, a delay in psycho-speech development occurs, reaching a degree of mental retardation. In most cases, instability of the cervical spine is observed with a high risk of developing spinal cord compression. In patients with manifestation of the disease after 4 years leading symptoms - skeletal disorders.

Diagnosis of type VII mucopolysaccharidosis

Laboratory diagnostics

To confirm the diagnosis of mucopolysaccharidosis VII, the level of urinary glucosamycline excretion is measured and the activity of beta-glucuronidase is measured. In the case of mucopolysaccharidosis VII, the total excretion of glycosaminoglycans in the urine increases and there is hyperexcretion of dermatan sulfate and heparan sulfate. The activity of beta-glucuronidase is measured in leukocytes or a culture of skin fibroblasts using an artificial fluorogenic substrate.

Prenatal diagnosis is possible by measuring the activity of beta-glucuronidase in the chorionic villus sampling biopsy 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 performed both within the mucopolysaccharidosis group and with other lysosomal accumulation diseases: mucolipidosis, galactosialidosis, sialidosis, mannosidosis, fucosidosis, GM1-gangliosidosis.

Treatment of mucopolysaccharidosis type VII

Effective methods are not developed. Conduct symptomatic treatment.

[1], [2], [3]