Chicago Center for Jewish Genetics Disorders - Ashkenazi Disorders: Gaucher Disease

Ashkenazi Disorders: Mendelian

Gene: Gaucher disease, Type 1 (GD1) is caused by a defect in the lysosomal glucocerebrosidase gene (GBA), which is located at 1q21. It encodes the enzyme glucocerebrosidase, and mutations lead to deficient enzyme activity and an accumulation of glucosylceramide and other glycolipids (GL1) in cells of the reticuloendothelial system (macrophages). This affects the liver, spleen, bone marrow, and occasionally, lung.

Mutations and testing: Four mutations account for 90% of the mutant alleles seen in the Ashkenazi Jewish population and ~50 to 60% of mutant alleles seen in the non-Ashkenazi Jewish population. These mutations are N370S, L444P, 84GG, and IVS2+1. Assay of the enzyme glucocerebrosidase can detect people who are affected with Gaucher disease but this testing is NOT accurate for carrier detection due to an overlap of the range of activity seen in carriers with that seen in non-carriers.

Traits: Gaucher disease, Type 1 is characterized by hepatosplenomegaly, hypersplenism with anemia and thrombocytopenia, and very rarely, pulmonary disease. Bone disease occurs in 70 to 100% of patients and can cause very painful bone crises (mini "strokes" in the bone), osteopenia, focal or sclerotic lesions, and osteonecrosis. NO neurological symptoms are seen in Type 1.

Treatment: Gaucher disease is very effectively treated with enzyme replacement therapy. This consists of intravenous infusion of recombinant human glucocerebrosidase every two weeks. Bone marrow transplantation is not considered necessary in Type 1. Substrate synthesis inhibitors, which may reduce the accumulation of glucocerebroside, and gene therapy are being investigated as potential future therapies.

Gaucher Disease from Geneclinics.org
http://www.genetests.org/profiles/gaucher

Reviewed by Dr. Joel Charrow, Children's Memorial Hospital.
1/03

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This page last updated on January 10, 2003.