Gaucher disease

Abstract

Gaucher disease (GD) is the most common entity of lysosomal storage diseases. It is a rare autosomal recessive genetic disorder, caused by a deficiency of the lysosomal enzyme β-glucocerebrosidase, which leads to an accumulation of its substrate, glucosylceramide, in macrophages. Clinical signs and symptoms include neurologic dysfunctions, bone infarcts and malformations, hepatosplenomegaly, and hypersplenism leading to anemia, neutropenia, and thrombocytopenia, and which are caused by Gaucher cell infiltration of the bone marrow, spleen, and liver. The phenotype is variable, but three basic clinical forms of GD have been identified according to the degree of neurological involvement. Type 1 GD is the most common and generally does not cause neurological damage, while types 2 and 3 are characterized by neurological deterioration, either severe in type 2 or variable in type 3. The diagnosis of GD can be confirmed demonstrating the deficiency of acid glucoce-rebrosidase activity in leukocytes. Mutations in the GBA1 gene must be identified, as they may have prognostic value in some cases. Specific treatment consists of intravenous enzyme replacement therapy using one of the currently available molecules (imiglucerase, velaglucerase, or taliglucerase). Oral substrate reduction therapy that inhibits glucosylceramide biosynthesis (miglustat or eliglustat) can also be used. Treatment is most effective when it begins in the early stages, therefore, a rapid diagnosis is essential.