Gaucher's disease: a review for the internist and hepatologist.

Gaucher's disease is the autosomally recessively inherited deficiency of the lysosomal enzyme glucocerebrosidase. Increasing storage of glucocerebrosides leads to a multi-system disease which prevalence ranges between 1:30,000 and 1:50,000 in most countries. Thus only a minority of physicians are aware of this diagnosis, of the symptoms that should lead to its consideration, and of the availability of specific tests that confirm it. Because Gaucher's disease often affects the liver, hepatologists may care for Gaucher patients. This review provides the internist and hepatologist with practical information about recent advances in the management of the non-neuronopathic type I of Gaucher's disease. Gaucher's disease, type 1 should be considered when unexplained spleno- and hepatomegaly, anemia, thrombocytopenia, or skeletal disease are present, particularly in combination. The diagnosis is established by an assay for glucocerebrosidase activity in peripheral leukocytes. Lack of awareness and of widespread availability of the enzyme assay has as yet limited its application in clinical practice, and led to many cases of Gaucher's disease being diagnosed by bone marrow and liver biopsy. Alglucerase, placental enzyme preparation of glucocerebrosidase, has proven effective in more than 1,000 patients worldwide. Recently, alglucerase has been exchanged by the recombinant enzyme preparation imiglucerase, which is equally effective and safe. Enzyme replacement improves hematological abnormalities, hepato-splenomegaly, and quality of life in a matter of a few months. Regression of skeletal complications is usually seen only after 3-4 years. Recently gene therapy trials, which center on autotransfusion of retrovirally transduced stem cells, have successfully been started.