Gaucher Disease
New Approaches to an Ancient Disease
Henry J. Mankin, MD; Daniel I. Rosenthal, MD; Ramnik Xavier, MD, PhD

Gaucher disease is an uncommon autosomal genetic disorder characterized by the deposit of large amounts of a lipid, glucosylceramide, in the cells of the spleen, liver, and bone marrow.

The disease occurs because of a genetic fault in the production of a specific enzyme, b-glucosidase, which ordinarily destoys the lipid material.

Bone disease consists of a failure to remodel (Erlenmeyer-flask deformity), osteopenia, and medullary and subchondral osteonecrosis, all of which cause, in some patients, severe crippling and disability.

A major discovery was the capacity to modify the b-glucosidase by mannose substitution, which allowed it to enter the cell and destroy the lipid. This treatment has greatly altered the lives of patients with this disease, and, when sufficient enzyme was given, has greatly restored the patient’s osseous structure.

Gaucher disease is an uncommon disorder, but it offers a spectacular model of the approach now being taken to define and treat many genetic disorders, a number of which are orthopaedic in their manifestations.

Gaucher disease is a rare genetic disorder that is classified as a lipid lysosomal storage disease. A product of cell-membrane breakdown, glucosylceramide is stored in the lysosomal bodies of the cells of the reticuloendothelial system as a result of a genetic error in glucosylceramide-hydrolase (b-glucosidase) production. The disease is transmitted as an autosomal recessive and most often causes marked splenomegaly, hematological disorders, and bone abnormalities, all of which may lead to serious functional impairment.

This Current Concepts Review describes the disorder in some detail, with particular attention to the osseous manifestations. Although the disease is uncommon, many orthopaedists see patients with osteonecrosis or bleeding disorders and should be concerned about the possibility that these findings may be manifestations of Gaucher disease. Of equal importance, however, is an understanding of the extraordinary strides made by scientists and clinicians in the …

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