Sly syndrome

Sly syndrome
Other names	β-glucuronidase deficiency, β-glucuronidase deficiency mucopolysaccharidosis,
Sly syndrome has an autosomal recessive pattern of inheritance.
Specialty	Endocrinology

Sly syndrome,also calledmucopolysaccharidosistype VII(MPS-VII), is anautosomal recessivelysosomal storage diseasecaused by a deficiency of theenzymeβ-glucuronidase.This enzyme is responsible for breaking down large sugar molecules calledglycosaminoglycans(AKA GAGs, or mucopolysaccharides). The inability to break down GAGs leads to a buildup in many tissues and organs of the body. The severity of the disease can vary widely.

Signs and symptoms

The most severe cases of Sly syndrome can result inhydrops fetalis,which results infetaldeath or death soon after birth. Some people with Sly syndrome may begin to have symptoms in early childhood. Symptoms can includean enlarged head,fluid buildup in the brain,coarse facial features,enlarged tongue,enlarged liver,enlarged spleen,problems with theheart valves,and abdominalhernias.People with Sly syndrome may also havesleep apnea,frequent lung infections, and problems with vision secondary to cloudycorneas.Sly syndrome causes various musculoskeletal abnormalities that worsen with age. These can include short stature, joint deformities,dysostosis multiplex,spinal stenosis,andcarpal tunnel syndrome.

While some individuals have developmental delay, others may have normal intelligence.However, the accumulation of GAGs in the brain usually leads to the slowing of development from ages 1–3, and then a loss of previously learned skills until death.

Genetics

The defective gene responsible for Sly syndrome is located onchromosome 7.

Diagnosis

Most people with Sly disease will have elevated levels of GAGsseen in the urine.A confirmatory test is necessary for diagnosis. Skin cells andred blood cellsof affected people will have low levels of β-glucuronidase activity. Sly syndrome can also be diagnosed throughprenatal testing.

Treatment

Vestronidase alfa-vjbk(trade name Mepsevii), an enzyme replacement therapy which is a recombinant form of human β-glucuronidase, is approved by U.S. Food and Drug Administration for the treatment of Sly syndrome.Hematopoietic stem cell transplant(HSCT) has been used to treat other types of MPS diseases, but this is not yet available for MPS-VII. Animal experiments suggest that HSCT may be an effective treatment for MPS-VII in humans.

Prognosis

The life expectancy of individuals with MPS VII varies depending on the symptoms. Some individuals are stillborn, while some may survive into adulthood.

Epidemiology

MPS-VII is one of the rarest forms of MPS. It occurs in less than 1 in 250,000 births. As a family, MPS diseases occur in 1 in 25,000 births, and the larger family of lysosomal storage diseases occur in 1 out of 7,000 to 8,000 births.

History

Sly syndrome was originally discovered in 1972.It was named after its discovererWilliam S. Sly,an American biochemist who has spent nearly his entire academic career at Saint Louis University.