Sly Syndrome (Mucopolysaccharidosis Type VII)

Updated: Nov 10, 2015
  • Author: Maryam Banikazemi, MD; Chief Editor: Maria Descartes, MD  more...
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Overview

Background

The mucopolysaccharidoses (MPSs) are a group of inherited lysosomal storage disorders that are caused by a deficiency of specific lysosomal enzymes required for the degradation of glycosaminoglycans (GAGs) (mucopolysaccharides). MPSs show extensive genetic heterogeneity, both among and within loci.

Mucopolysaccharidosis type VII (MPS VII) is a very rare lysosomal storage disease. MPS VII, traditionally known as Sly syndrome, was characterized for the first time in a patient with skeletal features similar to those observed in other patients with MPS. Sly syndrome is caused by deficiency of the enzyme β -glucuronidase. [1] Historically, MPS VII is of interest because it was the first MPS (excluding the sex-linked gene for Hunter syndrome) for which the mutant gene was localized to chromosome 7.

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Pathophysiology

In MPS VII the molecular defect on the gene that encodes β-glucuronidase protein (GUSB) leads to deficiency of the enzyme β-glucuronidase. This enzyme is required for the breakdown of several GAGs, including dermatan sulfate (DS), heparan sulfate (HS), and chondroitin sulfate (CS). [2] Accumulation of DS, HS, and CS takes place in the lysosome of many systems and tissues, including the CNS. The pattern of urinary excretion of HS, DS, and/or CS may vary based on the subtype of MPS VII involved.

Genetics

The GUSB is located on chromosome 7q11.21-7q11.22, is 21-kb long, and contains 12 exons. The defect in GUSB is responsible for Sly syndrome. More than 45 mutation different mutations have been identified, approximately 90% of which were point mutations. The limited data reflect the severity of disease in part can be attributed to the genotype and residual catalytic enzyme activity.

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Epidemiology

Frequency

United States

MPS VII is extremely rare, and few cases have been described.

International

In his extensive study of MPSs in Northern Ireland in 1997, Nelson reported that no living cases of MPS VII were observed from 1958-1985. Three cases of nonimmune hydrops fetalis were believed to be MPS VII on the basis of placental histology and enzyme studies in the parents. [3]

Mortality/Morbidity

Only a small sample of cases is available from which to extrapolate mortality figures for MPS VII. Fetal deaths have been noted several times. In mild cases, survival to age 19-20 years has been reported. Upper respiratory tract infections, neurodegenerative complications, and GI tract conditions may contribute to reduced survival rates.

Sex

Males and females are affected in equal numbers. Transmission is autosomal recessive.

Age

As a point of emphasis, Sly syndrome is one of the few MPSs and lysosomal storage diseases that may be clinically evident at birth, and even the most severe defects may appear prenatally. In other forms, defects may present during the first years of life. In the milder forms, clinical features may not be evident until later.

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