GAUCHER DISEASE

Gaucher disease, a condition transmitted by autosomal recessive inheri tance, results from a genetic defect in beta-glucosidase, an enzyme wh ich degrades sphingolipids. Deficiency in beta-glucosidase leads to ac cumulation of its substrate, glycosylceramide, in macrophages and, in the more severe cases, in neurons. Clinically, splenomegaly, hepatomeg aly, bone destruction, cytopenia, and in some cases, central neurologi cal lesions develop. Three phenotypes have been described according to the absence (type 1) or presence of neurological involvement (type 2: severe, type 3: intermediate severity). The disease occurs in patient s of all ethnic origins but type 1 is particularly well known in Ashke nese Jews and type 3 is found in the Swedish province of Norrbottnie. About forty mutations of the beta-glucosidase gene have been identifie d. Pour account for 80% of the known mutations (1226G, 1448C, 84GG, IV S2+1). Residual enzyme activity of mutant beta-glucosidase explains so me of the phenotypic variations. The phenotype resulting from the 1226 G mutation has sufficient enzyme activity for degradation of gangliosi des in the brain, explaining the absence of neurological involvement i n patients with this allele. Treatment is based on enzyme supplementio n: blood parameters return to normal and the volume of the spleen and Liver are greatly reduced after 6 months. In infants with very severe disease, bone marrow graft may be used.