Grau A J, Schwaninger M, Goebel H H, Beck M
Neurologische Universitätsklinik Heidelberg.
Nervenarzt. 2003 Jun;74(6):489-96. doi: 10.1007/s00115-003-1513-6. Epub 2003 May 20.
Fabry's disease is an x-linked, recessive, lysosomal storage disorder that results from deficient alpha-galactosidase A activity with pathological sphingolipid deposition mainly in endothelium, smooth muscle cells, kidneys, central and peripheral nervous system, and myocardium. Clinical manifestation mostly occurs during childhood and adolescence with severe pain attacks or chronic pain mainly in hands and feet, hypohydrosis, and skin lesions (angiokeratoma). In more advanced disease stages, renal and cerebrovascular complications develop with proteinuria and later renal failure and cerebral ischemia caused by cerebral microangiopathy, dilatative arteriopathy, or cardiac embolism. Heterozygote female carriers are severely affected more often than was previously considered. The diagnosis is based on the detection of deficient alpha-galactosidase A activity in leukocytes, fibroblasts, or tissue biopsies. Two randomised placebo-controlled studies showed that enzyme replacement is effective by demonstrating either reduced pain or reduced tissue sphingolipid deposition. Early diagnosis of Fabry's disease is important in view of these new causal therapeutic options.
法布里病是一种X连锁隐性溶酶体贮积症，由α-半乳糖苷酶A活性缺乏引起，病理鞘脂主要沉积在内皮细胞、平滑肌细胞、肾脏、中枢和外周神经系统以及心肌中。临床表现大多发生在儿童期和青春期，主要表现为严重的疼痛发作或慢性疼痛，主要累及手足，少汗，以及皮肤病变（血管角质瘤）。在疾病的更晚期，会出现肾脏和脑血管并发症，表现为蛋白尿，随后发展为肾衰竭以及由脑微血管病、扩张性动脉病或心脏栓塞引起的脑缺血。杂合子女性携带者受影响的严重程度比以前认为的更常见。诊断基于检测白细胞、成纤维细胞或组织活检中α-半乳糖苷酶A活性的缺乏。两项随机安慰剂对照研究表明，酶替代疗法通过减轻疼痛或减少组织鞘脂沉积而有效。鉴于这些新的病因治疗选择，法布里病的早期诊断很重要。
