Enzyme Replacement in Gaucher Disease

118 Gaucher disease is the most common lysosomal storage disorder (Box 1). A defi ciency of the enzyme glucocerebrosidase (Figure 1) causes accumulation of the glycolipid glucocerebroside in macrophages throughout the body. In the viscera, glucocerebroside arises mainly from the biodegradation of red and white blood cells. In the brain, glucocerebroside arises from the turnover of complex lipids during brain development and the formation of the myelin sheath of nerves. The disease may be discovered as an incidental fi nding in the elderly because of mild thrombocytopenia or splenomegaly, or it may present early in life with hepatosplenomegaly, thrombocytopenia, anemia, and bone lesions. Until 1990, treatment consisted only of palliative measures such as splenectomy and hip replacement. The development of enzyme replacement therapy for Gaucher disease, that is, exogenous administration of the missing enzyme, is a triumph of translational medicine. At the same time, powerful commercial interests may have been infl uential in physicians adopting a high-dose rather than a low-dose treatment schedule. Moreover, the high cost of enzyme replacement therapy forces us to consider what society can afford in the way of palliative treatments for very rare diseases.