La maladie de Gaucher est l'une des rares maladies genetiques accessible a un traitement specifique. C'est une pathologie hereditaire du metabolisme des sphingolipides, de transmission autosomique recessive, due au deficit en β-glucosidase acide. Le deficit enzymatique conduit a l'accumulation pathologique du substrat non degrade (glucosylceramide) dans les lysosomes. Cette surcharge metabolique est responsable d'une maladie multisystemique avec hepatosplenomegalie, anemie, thrombopenie et atteinte osseuse. L'atteinte neurologique est plus rare, definissant les maladies de Gaucher de type 2 et 3. En dehors de la communaute juive ashkenaze ou predominent trois alleles recurrents, il existe une large diversite des lesions moleculaires. Les correlations genotype-phenotype sont imparfaites. L'enzymotherapie substitutive est disponible depuis 1991. L'enzyme, initialement d'origine extractive (alglucerase), puis recombinante (imiglucerase) a transforme le pronostic de l'immense majorite des patients atteints de maladie de Gaucher de type 1. L'amelioration des parametres cliniques et hematologiques est objective en six a 12 mois, tandis que la reponse osseuse est plus longue a obtenir. L'atteinte neurologique des maladies de Gaucher de type 2 et 3 ne repond pas a l'enzymotherapie substitutive, plaidant en faveur de la poursuite des recherches sur les petites molecules inhibitrices et la therapie genique.
Gaucher disease (GD) is one of the most prevalent lysosomal storage disorders and one of the rare genetic diseases for which therapy is now available. 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 diseases. Outside of the Ashkenazi Jewish community, a high molecular diversity is observed. Clarification of genotype-phenotype relationship and the identification of modifier loci that impact on Gaucher disease phenotypes remain a critical area for research. Recombinant glucocerebrosidase (imiglucerase) is an effective mean of treating type 1 Gaucher disease and should be initiated early on in life. Amelioration of hepatosplenomegaly and of haematological manifestations is usually apparent within six months. Bone disease responds more slowly. Imiglucerase has recently been approved for the treatment of type 3 Gaucher disease. Enzyme replacement therapy cannot reverse the neurological deficits in type 2 or type 3 Gaucher disease. This should prompt further research on substrate deprivation and gene therapy.