Blood Rev 1988 Mar;2(1):59-70

Gaucher disease

Beutler E
Department of Basic and Clinical Research, Research Institute of Scripps Clinic,
La Jolla, CA 92037.

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