The review describes the clinical, biochemical and molecular genetic characteristics of autosomal recessive mucopolysaccharidosis type III, or Sanfilippo syndrome. This is a genetically heterogeneous group of rare, but similar in nature, diseases caused by a deficiency of one of the four lysosomal enzymes involved in the degradation of heparan sulfate. All types of mucopolysaccharidosis III are characterized by severe degeneration of the central nervous system in combination with mild somatic manifestations, which is explained by the accumulation of high concentrations of heparan sulfate in the lysosomes of various cells, including the central nervous system. The primary biochemical defect in the most common type of mucopolysaccharidosis IIIA, occurring with a frequency of 1 : 105 and presented in 60% of all cases of the disease, is heparan-N-sulfatase, or sulfamidase deficiency. Mucopolysaccharidosis IIIB type occurs twice less often and accounts for about 30% of all cases of Sanfilippo syndrome. It is caused by the presence of inactivating mutations in the lysosomal -N-acetylglucosaminidase gene. Mucopolysaccharidosis IIIC and IIID are 4% and 6%, and occur at frequencies of 0.7 and 1.0 : 106. Mucopolysaccharidosis IIIC is caused by inactivating mutations in the gene of membrane-bound lysosomal acetyl-CoA:-glucosaminid-N-acetyltransferase, or N-acetyltransferase. Mucopolysaccharidosis IIID is based on the deficiency of lysosomal N-acetylglucosamine-6-sulfatase. The role of experimental models in the study of the biochemical basis of the pathogenesis of Sanfilippo syndrome and the development of various therapeutic approaches are discussed. The possibility of neonatal screening, early diagnosis, prevention and pathogenetic therapy of these severe lysosomal diseases are considered. As an example, a clinical case of diagnosis and treatment of a child with type IIIB mucopolysaccharidosis is presented.
Lysosomal storage diseases. Mucopolysaccharidosis type III, sanfilippo syndrome