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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 pedigree of Fabry’s disease with repeated stroke as the main clinical manifestation and to analyze its clinical features and gene mutation status. Methods The clinical features and head MRI were collected from this proband and its family members. Skin biopsy was performed on probands and the activity of α-galactosidase A (α-galA) was examined. Extract the blood of proband and his brother and mother for DNA sequencing. Results All 3 pediatric patients had recurrent stroke, accompanied by acral pain, cutaneous angioma and oligoarthritis. Imaging showed the basal ganglia, multiple brain cavity disease. Skin tissue electron microscopy shows endothelial cells and pericytes within a large number of secondary lysosome structure, secondary lysosomes like fingerprint structure. Pro-α-galA activity significantly decreased, GLA gene test found c.672T> G, p.N224K hemizygous mutation (male X-chromosome homozygous mutation). Conclusions The Fabry pedigree is characterized by recurrent stroke in the basal ganglia and brainstem, with typical pathological and enzymatic evidence. The mutation of c.672T> G, p.N224K was found in the GLA gene test, which has not been reported in the literature .