Gaucher disease.

Abstract

Gaucher disease is a glycolipid storage disorder characterized by accumulation of glucocerebroside in the liver, spleen, and bones, and caused by a deficiency of glucocerebrosidase. Glucocerebrosidase cDNA has been cloned and sequenced, and much has been learned about the synthesis and processing of this enzyme. Inherited as an autosomal recessive disorder, Gaucher Disease is relatively common among Ashkenazi Jews. In its most common form, designated Type 1 or adult type of Gaucher disease, the central nervous system is spared. Several organ systems may be involved, including not only the hematopoietic tissues and bones, but also the lungs. Diagnosis can be achieved without marrow examination by estimating the glucocerebrosidase (beta-glucosidase) activity of the peripheral blood leukocytes. Currently available conventional therapy is purely symptomatic in nature, including orthopedic procedures and splenectomy. On an experimental basis, splenectomy may be partial instead of total. Because the disease is due to an abnormality of the monocyte-macrophage system, cells that arise from the hematopoietic stem cell, and because the central nervous system is spared it has been considered a very suitable candidate for experimental therapeutic intervention. Bone marrow transplantation has been attended with limited success, enzyme therapy has not yet been successful, and studies utilizing gene transfer are underway.