Frenkel E P
Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas 75235-8852.
Am J Med Sci. 1993 May;305(5):331-44. doi: 10.1097/00000441-199305000-00014.
Gaucher disease, the most common form of lysosomal storage disease, is the result of autosomal recessive inheritance of a lysosomal enzyme glucocerebrosidase deficiency, which produces defective hydrolysis of glucosylceramide that accumulates in reticuloendothelial (tissue macrophage) cells. The current review focuses on Type 1 (the nonneuronopathic) or adult Gaucher disease and defines the clinical manifestations (splenomegaly, hepatomegaly, bony lesions, and clinical metabolic dysfunction) in relationship to the known enzymatic defect. The clinical diversity and variability in symptoms and signs, the age at onset of the clinical manifestations and their rate of progression, and the heterogeneity of the organs involved are reviewed. Extensive delineation of the nature of the enzyme defect and the recent molecular characterization of the enzyme mutants has not provided an explantation for the remarkable clinical phenotypic heterogeneity. Enzyme assays now provide an excellent method for diagnosis. Effective enzyme replacement therapy emphasizes the value of early diagnosis and has altered the costs and potential risks of older therapeutic indications for splenectomy or cytokine therapy. Enzyme efficacy raises questions about the specific indications for replacement treatment and the most desirable rate and duration of enzyme delivery.
戈谢病是最常见的溶酶体贮积病，是由于溶酶体酶葡糖脑苷脂酶缺乏的常染色体隐性遗传所致，该酶缺乏会导致葡糖神经酰胺水解缺陷，进而在网状内皮（组织巨噬细胞）细胞中蓄积。本综述聚焦于1型（非神经病变型）或成人戈谢病，并结合已知的酶缺陷阐述其临床表现（脾肿大、肝肿大、骨病变及临床代谢功能障碍）。对症状和体征的临床多样性及变异性、临床表现的发病年龄及其进展速度，以及受累器官的异质性进行了综述。对酶缺陷本质的广泛描述以及酶突变体的近期分子特征分析，均未能解释显著的临床表型异质性。酶测定法目前是一种出色的诊断方法。有效的酶替代疗法凸显了早期诊断的价值，并改变了脾切除术或细胞因子疗法等传统治疗方法的成本及潜在风险。酶的疗效引发了关于替代治疗的具体适应证以及最适宜的酶递送速率和持续时间的问题。
