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

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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 Morquio’s 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 β-galactosidase deficiency and is an allelic variant of GM1 gangliosidosis. The cause of MPS VI, or Maroto–Lamy syndrome, and MPS VII, or Sly syndrome, is hereditary deficiency of arylsulfatase B and β-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.

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About the authors

Victoria N. Gorbunova

St. Petersburg State Pediatric Medical University

Author for correspondence.
Email: vngor@mail.ru

PhD, Dr. Sci. Professor, Department of Medical Genetics

Russian Federation, Saint Petersburg

Natalia V. Buchinskaia

St. Petersburg State Medical Diagnostic Center (Genetic Medical Center)

Email: nbuchinskaia@gmail.com

MD, PhD, Pediatrician, Geneticist of Consulting Department

Russian Federation, Saint Petersburg

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Supplementary files

Supplementary Files
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1. Fig. 1. An example of hypermobility of the interphalangeal joints of the hand in a patient with severe MPS IVA

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2. Fig. 2. Phenotype of a girl with type IV MPS

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3. Fig. 3. The appearance of the hand of a girl with type IV MPS, clinodactyly of 5 fingers

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4. Fig. 4. External view of a patient with MPS VI type, severe form

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5. Fig. 5. X-ray of the hands of a patient with type VI MPS

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6. Fig. 6. X-ray of the thoracic and lumbar spine with hip joints: biconvex shape of the thoracic and lumbar vertebrae, posterior wedge-shaped vertebrae and lingual vertebrae with a beveled anteroposterior angle. The thoracic kyphosis is flattened, its height is shifted caudally. Body hypoplasia Th11. S-shaped deformity of the lower thoracic–lumbar spine, with an upper right-sided arch ~180, a lower left-sided arch ~280. The acetabulum is shallow, the roofs are sloping, and the heads of the femurs are flattened. The femoral necks are straightened

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