Summary
Gaucher disease is a lysosomal storage disorder caused by a deficiency in glucocerebrosidase (also referred to as glucosylceramidase or acid beta-glucosidase) or, in rare cases, by a deficiency in the activator protein saposin C. The disease is characterised by the presence of glucosylceramide (or glucocerebroside) deposits in the reticuloendothelial cells of the liver, spleen and bone marrow. The incidence of Gaucher disease in the general population is around 1 in 60 000, but may be as high as 1 in 1000 among Ashkenazi Jews. The prevalence is around 1 in 100 000. The clinical manifestations are extremely variable. Classically, three main phenotypes can be distinguished. Type 1 is the chronic and nonneurological form representing 95% of all cases. It is a heterogeneous disease characterised by the association of organomegaly (spleen, liver), bone disease (pain, bone infarcts, osteonecrosis) and cytopaenia (thrombocytopaenia, anaemia and, more rarely, neutropaenia). The activity of some biological markers - including chitotriosidase (an angiotensin converting enzyme), ferritin and tartrate-resistant acid phosphatase (TRAP) - is also increased. Type 2 is the acute neurological form, characterised by early-onset (during the first year of life) brainstem dysfunction, rapid progression and associated organomegaly. Type 3 is the subacute neurological form and is characterised by progressive encephalopathy (oculomotor apraxia, epilepsy and ataxia), associated with the manifestations present in the type 1 disease with onset during childhood or adolescence. The encephalopathy may be the first sign of the disease or may occur later in the disease course. A perinatal-lethal form has also been reported and manifests as a decrease or absence of foetal movements or anasarca. Gaucher disease is transmitted as an autosomal recessive trait and is caused by mutations in the GBA gene (1q21). Diagnosis can be confirmed by measurement of the level of glucocerebrosidase in circulating leukocytes. At present, two specific treatments for Gaucher disease are commercially available, but enzyme substitution therapy using the analogue imiglucerase remains the treatment of choice and is indicated for use in patients with type 1 or type 3 disease. Substrate reduction therapy using miglustat provides an alternative second-line treatment. It is important that patients with Gaucher disease receive treatment before the appearance of sequelae that are unresponsive to these therapies. *Author: Drs T. Billette, J. Stirnemann and N. Belmatoug (October 2006)*.
