以反复缺血性脑卒中为突出表现的法布雷病1例报道及家系分析

Recurrent ischemic stroke as a predominantly manifestation in a Fabry disease family

目的对一个以反复脑卒中为主要临床表现的法布雷病(Fabry病)家系进行调查,分析其临床特点和基因突变情况。方法收集该例先证者及其家族成员的临床表现、头颅MRI检查资料。对先证者行皮肤活检,检测α-半乳糖苷酶A(α-galA)的活性。提取先证者及其弟弟、母亲的血液,进行DNA测序。结果家系中3例患者均出现反复发作脑卒中,伴有肢端疼痛、皮肤血管角质瘤及少汗等表现。影像学均表现为基底节、脑干多发性腔隙病变。皮肤组织电镜下可见血管内皮细胞及周细胞内大量次级溶酶体结构,次级溶酶体内似有指纹结构。先证者α-galA活性明显下降,GLA基因检测发现c.672T>G,p.N224K半合子突变(男性X染色体纯合突变)。结论 Fabry家系以基底节和脑干反复脑卒中为突出临床表现,具有典型的病理学和酶学证据,GLA基因检测发现c.672T>G,p.N224K半合子突变,该突变未见文献报道。

Objective To investigate a Fabry disease family with recurrent ischemic stroke, and analyze clinical characteristics and the gene mutations. Methods The clinical manifestations and neuroimaging data（MRI） of the proband and family members were collected. Skin biopsy was performed and α-galactosidase A（α-galA） enzymatic activity was detected in the proband. Genetic analysis was performed by DNA sequencing in all family members. Results All of the three patients developed recurrent stroke, accompanied by acroparesthesias, angiokeratoma and hypohidrosis. The cranial MRI in all patients showed multiple lesions of lacunar infarctin basal ganglia and brainstem. Electron microscopy showed massive storage of glycosphingolipids in the secondary lysosomes in the endothelial and smooth muscle cells of a skin arteriole. The α- galA activity of the proband was significantly decreased, and by sequencing of the α- galA gene,c.672T〉G,p.N224K hemizygous mutation（X chromosome homozygous mutation in male） were detected. Conclusion Recurrent stroke in the basal ganglia and brainstem is the prominent clinical manifestation in this Fabry disease family,which has typical pathologic and enzymatic analysis evidences. Gene sequencing showed c.672T〉G,p.N224K hemizygous mutation, which has not been reported.