Sly syndrome

An overview of Sly syndrome, a rare genetic disorder

Sly syndrome, also known as mucopolysaccharidosis type VII (MPS VII), is a rare autosomal recessive lysosomal storage disorder caused by a deficiency of the enzyme beta-glucuronidase. This enzyme deficiency leads to the accumulation of glycosaminoglycans (GAGs) in various tissues and organs, resulting in a wide range of clinical manifestations.

Genetics

Sly syndrome is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the defective gene, one from each parent, to manifest the disease. The gene responsible for Sly syndrome is located on chromosome 7 and is known as the GUSB gene. Mutations in this gene lead to reduced or absent activity of the beta-glucuronidase enzyme.

Pathophysiology

The deficiency of beta-glucuronidase in Sly syndrome results in the accumulation of glycosaminoglycans such as dermatan sulfate, heparan sulfate, and chondroitin sulfate in the lysosomes of cells. This accumulation disrupts normal cellular function and leads to the progressive damage of tissues and organs.

Clinical Features

The clinical presentation of Sly syndrome can vary widely among affected individuals. Common features include:

• Hepatosplenomegaly
• Skeletal dysplasia
• Developmental delay
• Hydrops fetalis in severe cases
• Cardiac abnormalities
• Corneal clouding

Diagnosis

Diagnosis of Sly syndrome is typically made through a combination of clinical evaluation, biochemical testing, and genetic analysis. Measurement of beta-glucuronidase activity in leukocytes or fibroblasts can confirm the diagnosis. Genetic testing can identify mutations in the GUSB gene.

Management

Currently, there is no cure for Sly syndrome, and treatment is primarily supportive and symptomatic. Management may include:

• Enzyme replacement therapy
• Hematopoietic stem cell transplantation
• Symptomatic treatment for cardiac and respiratory complications

Prognosis

The prognosis for individuals with Sly syndrome varies depending on the severity of the disease. Early diagnosis and intervention can improve quality of life and outcomes for affected individuals.

Related pages

• Mucopolysaccharidosis
• Lysosomal storage disorder
• Autosomal recessive disorder

• 

  Sly syndrome