Disease Information

Gaucher disease is a lysosomal storage disorder caused by a mutation in the gene responsible for the production of the enzyme β-glucocerebrosidase. This lysosomal enzyme normally breaks down glycosphingolipids derived from physiological turn-over of membranes, particularly of blood cells. More than 200 mutant alleles have been identified.^[1] As a result of mutation, β-glucocerebrosidase activity is insufficient to prevent accumulation of a glycosphingolipid called glucocerebroside in the lysosomes of cells, mainly of the tissue macrophage system. Glucocerebroside-engorged macrophages, termed Gaucher cells, accumulate in organs. Gaucher cell storage leads to a further cascade of physiopathologic events, including the elicitation of a chronic inflammatory and hypermetabolic state. Clinically, this may translate into infiltration with masses of Gaucher cells of the organs of the reticuloendothelial system with secondary consequences such as hepatomegaly, splenomegaly, thrombocytopenia, anemia, skeletal pathology, pulmonary hypertension and interstitial lung disease, and—in a minority—central neurological involvement.^[2]

Gaucher disease probably affects fewer than 10,000 people worldwide.^[3] Recognizing the signs and symptoms of Gaucher is critical as early diagnosis and intervention are key.

References:

1. Beutler E, Gelbart T, Scott C. Hematologically important mutations: Gaucher disease. Blood Cells Mol Dis 2005;35:355-64.

2. Beutler E, Grabowski GA. Gaucher disease. In: Scriver C, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular bases of inherited disease. 8th ed. New York: McGraw-Hill; 2001:3635-3668.

3. Grabowski G. Gaucher disease: Enzymology, genetics, and treatment. In: Harris H, Hirshchorn K, eds. Advances in Human Genetics. New York, NY: Plenum Press; 1993;21: 377-441.