Sly syndrome


Sly syndrome

Description, Causes and Risk Factors:

Alternative Name: Mucopolysaccharidosis type VII or MPS VII.

An autosomal recessive disorder due to a deficiency of a beta-glucuronidase (?-glucuronidase); defective lysosomal degradation of dermatan sulfate, heparan sulfate, and chondroitin sulfate; cellular function disrupted in most tissues.

Sly syndrome belongs to a family of disorders identified as lysosomal storage diseases (LSD), and historically as the mucopolysaccharidoses. This disorder is characterized by the lysosomal accumulation of glucuronic acid-containing glycosaminoglycans (dermatan, heparan, and chondroitin 4-, and 6-sulfates) as a consequence of deficiencies in the lysosomal hydrolase, ?-glucuronidase.

Sly syndrome is inherited as an autosomal recessive genetic trait. Symptoms develop due to a deficiency of the enzyme beta-glucuronidase. The gene responsible for this disorder is located on the long arm of chromosome 7 (7q21.11) and has been termed the GUSB gene spanning 21 kb and comprising 12 exons that encode a 629 amino acid glycoprotein. Active ?-glucuronidase functions as a homotetrameric complex. Two different transcripts are generated from the GUSB gene as a consequence of an alternative splicing event that removes exon 6 from one of the two mRNAs. More than 30 different mutations have been identified in the GUSB gene resulting in Sly syndrome. Identified mutations include missense, nonsense, frameshift, and splice site mutations. Complicating the diagnosis of the inheritance of mutant alleles of GUSB is the presence of several pseudogenes on chromosomes 5, 6, 7, 20, 22 and Y. These pseudogenes can be detected with probes from exons 2, 3, 4, 6, 7, and 11 of the wild-type GUSB gene.

Sly syndrome is extremely rare, affecting only about one in one million births. Fewer than 100 cases have been reported in the United States. Males and females are affected in equal numbers.

Symptoms:

    Coarse facial features.

  • Phalanges are shortened and trapezoidal in shape.

  • Hepatosplenomegaly.

  • Protruding sternum.

  • Dystosis multiplex (enlarged skull, thickened calvarium, premature closure of lamboid and sagittal sutures, shallow orbits, enlarged J-shaped sella and abnormal spacing of the teeth with dentigerous cysts).

  • Anterior hypoplasia of the lumbar vertebrae.

  • The epiphyseal centers not well developed, the pelvis is poorly formed with small femoral heads and coxa valga.

  • The clavicles are short, thick and irregular and the ribs are oar shaped.

  • Stomach swelling.

Diagnosis:

Clinical evaluation that includes a detailed patient history and specialized tests that measure the level of beta-glucuronidase activity in skin fibroblasts or blood leukocytes. Prenatal diagnosis is also possible through amniocentesis or chorionic villus sampling for beta-glucuronidase activity.

The diagnosis of Sly syndrome may be confirmed thorough two tests that are used to determine whether a person has Sly syndrome. Urine measures the amount of GAG (glycosaminoglycans)in the urine. Individuals with Sly syndrome have abnormally large amounts of GAG in their urine. An enzyme assay measures the amount of the enzyme, beta-glucuronidase in blood or tissue samples, confirming a diagnosis. Individuals with sly syndrome have very low amounts of this enzyme in their cells.

Treatment:

There is no known cure for Sly syndrome, but there are many treatments that can be administered to delay symptom progression and to improve the quality of life in affected individuals.

The treatment of Sly syndrome is symptomatic and supportive. Bone deformities and hernias may require surgical correction. Ocular and cardiovascular abnormalities may also be treated surgically. Patients with MSP storage disorders may be sensitive to anesthesia because of malformations in the airway or cervical spine; therefore, precautions should be taken prior to surgery. Genetic counseling will be helpful for people with Sly syndrome and their families.

Enzyme replacement therapy and bone marrow transplantation are being investigated for the treatment of this disorder. Scientific study of these therapies in animal models raises the hope that they may someday be made available to people with genetic disorders such as Sly syndrome or other Mucopolysaccharidoses. Neither therapy has been attempted yet in humans.

Disclaimer: The above information is educational purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.

DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.

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