Gaucher disease (GD) is a rare, genetic, autosomal recessive lysosomal storage disease with multi-system manifestations caused by a deficiency of the lysosomal enzyme glucocerebrosidase, which leads to an accumulation of its substrate glucosylceramide (glucocerebroside) in macrophages of various tissues with an inflammatory response and a release of cytokines. In general population its incidence is approximately 1/40 000 to 1/60 000, rising to 1/800 in Ashkenazi Jews. Clinical features comprise cytopenias, splenomegaly, hepatomegaly, and bone lesions. Non-neuronopathic type-1 Gaucher disease, which affects the majority of patients (90% in Europe and USA), is characterized by visceral effects, whereas neuronopathic types 2 and 3 are dominantly associated with neurological impairment. The diagnosis of GD can be confirmed by the deficient acid glucocerebrosidase activity in peripheral blood leukocytes. Patients with type 1 GD, and even carriers of one gene mutation have predisposition to develop Parkinsons disease, and there is increased risk of some neoplasia in GD patients. Disease-specific treatment of type 1 GD consists of intravenous enzyme replacement therapy (ERT) with one of the available enzymes (imiglucerase, velaglucerase, or taliglucerase) or oraly administered substrate reduction therapy (SRT) with inhibitors of glucosylceramide biosynthesis (miglustat or eliglustat). Currently there is no treatment for type 2 disease which is lethal early in the life.
20 - 23 May 2017
European Society of Endocrinology