Molecular Biology of Gaucher Disease: Therapeutic Strategies Utilizing Recombinant DNA Technology

摘要: Gaucher disease is caused by the deficiency of lysosomal glycoprotein glucocerebrosidase (EC 3.2.1.45, β-D-glucosyl- N-acylsphingosine glucohydrolase) in tissues, with resultant accumulation glucosylceramide within reticuloendothelial system (Brady, et al. 1965; Patrick, 1965). In particular, this glycolipid stored macrophage progenitor-derived cells, including osteoclasts, Kupffer and alveolar macrophages. Although lipid peripheral tissue derived predominantly from precursors present red white blood cell membranes, glucocerebroside central nervous may also derive gang1iosides. On basis clinical signs symptoms, it has proven useful to separate disorder into three major phenotypes (Barranger Ginns, press). Type 1 (chronic, non-neuronopathic), most common form, characterized hepatosplenomegaly, anemia, thrombocytopenia, bone complications. Patients type 2 (acute, neuronopathic) usually have symptom onset six months age, manifest cranialnerve brainstem abnormalities, as well other symptoms seen 1. 3 patients systemic similar those 1, but neurologic abnormalities appear during childhood or adolescence. contrast stereotypic course patients, a much broader variation time severity.