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Gaucher disease Volume 5, issue 6, Novembre-Décembre 1999

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Consultation de génétique. Laboratoire de biologie moléculaire, hôpital Broussais, 96, rue Didot, 75014 Paris.

Gaucher disease (GD) is one of the most prevalent lysosomal storage disorders and one of the rare genetic diseases now accessible to therapy. Partial deficiency of glucocerebrosidase is associated with parenchymal disease of the liver, spleen, and bone marrow with concomitant anaemia and thrombocytopenia in non-neuronopathic, type 1, Gaucher disease. Severe deficiency of glucocerebrosidase caused by disabling mutation is additionally associated with neurological manifestations in the less common type 2 and type 3 Gaucher disease categories. Outside of the Ashkenazi Jewish community, a high molecular diversity is observed, leaving about 30 % of alleles undetected. Clarification of genotype/phenotype relationship and the identification of modifier loci that impact on Gaucher disease phenotypes remain a critical area for research. Modified placental human glucocerebrosidase (alglucerase) and recombinant glucocerebrosidase (imiglucerase) are effective means of treating type 1 Gaucher disease. Amelioration of hepatosplenomegaly and of haematological manifestations is usually apparent within 6 months. Bone disease responds more slowly. Enzyme replacement therapy cannot reverse the neurological deficits in type 2 or type 3 Gaucher disease. Gene therapy for Gaucher disease was initiated in 1995. It is expected that improvments in this technology will provide a permanent cure for patients with this disorder.