Lysosomal storage diseases. Mucopolysaccharidosis types IV, VI, and VII – Morquio, Maroto–Lamy and Sly syndrome

Abstract

The review is devoted to the clinical, biochemical, and molecular genetic characteristics of autosomal recessive mucopolysaccharidoses (MPS) types IV, VI, and VII. MPS IV type, or Morquios syndrome, is represented by 2 types A and B. The cause of the most frequent MPS IVA is hereditary deficiency of galactose-6-sulfatase, due to the presence of inactivating mutations in the GALNS gene. The pathogenetic basis of the disease is associated with excessive accumulation in lysosomes, mainly of cartilage tissue of keratan sulfate and chondroitin-6-sulfate. Main clinical manifestations of MPS IVA are dwarfism and progressive deformity of the spine, sternum, and knees. The milder MPS IVB is due to hereditary -galactosidase deficiency and is an allelic variant of GM1 gangliosidosis. The cause of MPS VI, or MarotoLamy syndrome, and MPS VII, or Sly syndrome, is hereditary deficiency of arylsulfatase B and -glucuronidase, respectively. The pathogenesis of these diseases is due to the excessive accumulation of dermatan sulfate and, in the second case, additionally, heparan sulfate. Patients with type VI and VII MPS have a Hurler-like phenotype, but in the first case, intellectual deficiency are usually absent, while in Sly syndrome, moderate mental retardation is observed. The possibility of neonatal screening and early diagnosis of these MPS in order to increase the effectiveness of their prevention and treatment is discussed. The importance of experimental models for studying the molecular basis of the pathogenesis of these severe hereditary diseases and the development of various therapeutic approaches, such as bone marrow transplantation, enzyme replacement therapy and substrate-reducing therapy, is emphasized. Descriptions of clinical cases of MPS IVA and VI types are presented.