OBJECTIVE: To review the epidemiology, pathophysiology, clinical features, diagnosis, and treatment of Gaucher's disease, focusing on the role of enzyme replacement therapy. DATA SOURCES: a MEDLINE search (from 1984 to July 1995) of English-language literature pertaining to the treatment of Gaucher's disease was performed. Additional references were obtained by reviewing the references of pertinent articles identified through the search. Tertiary sources were also used. STUDY SELECTION AND DATA EXTRACTION: Articles with information on enzyme treatment were selected for review. Articles containing other interesting aspects of the disease or its treatment were also included. DATA SYNTHESIS: Gaucher's disease is the most common lipid storage disorder known and results from a genetic deficiency of the enzyme glucocerebrosidase (glucosylceramidase). Enzyme deficiency results in accumulation of glucocerebroside within the reticuloendothelial system. If may present with hepatosplenomegaly, bone marrow suppression, and bone lesions. The most common of the three subtypes, type 1, is non-neuronopathic. In the rare neuronopathic subtypes, type 2 or 3, there may also be nerve cell destruction within the central nervous system with acute brainstem dysfunction or progressive neurologic deterioration, respectively. In 1991, enzyme treatment became available with the marketing of alglucerase, a placentally derived modified form of glucocerebrosidase. In 1994, a recombinant DNA modified form of glucocerebrosidase, known as imiglucerase, was developed to replace alglucerase. Most published data on enzyme therapy are with alglucerase in patients with type 1 disease. A dosage regimen of 60 units/kg every 2 weeks for moderately to severely ill patients has been effective in reducing hepatosplenomegaly, improving anemia and thrombocytopenia, as well as improving weight gain and growth in children and increasing vigor and self-esteem in adults. Bone involvement is often slow to respond to therapy although pain is frequently improved. Controversy exists as to whether lower dosage regimens are as effective. The role of enzyme therapy in the rarer neuronopathic subtypes remains to be determined, but initial reports have been disappointing. CONCLUSIONS: Enzyme replacement therapy is available for the treatment of type 1 Gaucher's disease, resulting in clinical improvement with enhanced quality of life within the first year of treatment, although improvement in bone disease can take longer. Doses of 60 units/kg every 2 weeks are of clinical benefit to patients with moderate to severe disease. A number of lower dosage regimens have been evaluated in small groups of patients, with satisfactory clinical responses occurring in some of these patients.
Phenotypic Heterogeneity among GBA p.R202X Carriers in Lewy Body Spectrum Disorders
