一例女性Fabry病并发薄基底膜肾病及其家系调查

目的 了解具有两种遗传性疾病，即Fabry病并发薄基底膜肾病（TBMN）的临床病理和基因突变特点以及家系患病情况。 方法 总结分析本院收治的1例41岁女性Fabry病并发TBMN患者的临床病理特征和基因突变情况，同时对家系成员进行调查及相关检测。 结果 先证者呈现典型的Fabry病的肾外临床表现，包括皮疹、神经痛、眩晕、耳鸣、肥厚型心肌病等，同时亦有蛋白尿、镜下血尿及高血压等肾脏受累表现；肾活检光镜下病理改变为局灶性节段性肾小球硬化（FSGS），部分足细胞空泡变性；电镜下肾小球脏层上皮细胞胞质内多数髓磷脂小体形成，肾小球基底膜（GBM）弥漫性变薄，厚度为（216±31） nm。家系调查及基因突变检测显示先证者女儿除有典型Fabry病肾外表现外，亦有以血尿为主的肾脏症状。先证者的1个妹妹仅表现为镜下血尿。先证者及其女儿α-半乳糖苷酶 A（α-Gal A）活性分别为33和75活性单位（正常参考值为100~500活性单位），且2人均携带新发现的GLA基因突变——1208ins21 bp及COL4A3基因多态性——c:3627 G>A（p:M1209I）。仅表现为镜下血尿的先证者的妹妹仅携带COL4A3基因的c:3627 G>A（p:M1209I）多态性，α-Gal A活性正常，无GLA基因突变。 结论 对于Fabry肾病患者呈现血尿，尤其是表现为家族性血尿时，应考虑并认真排除并发TBMN的可能。

A female patient of Fabry disease complicated with thin basement membrane nephropathy and investigation of the kindred

Objective To elucidate the features of clinicopathology and mutation in Fabry disease complicated with thin basement membrane nephropathy (TBMN), and to investigate the kindred. Methods Data of clinicopathology and gene mutation of a female patient of Fabry disease complicated with TBMN admitted to the Department of Nephro]ogy in our hospital were analyzed. Members of her kindred were investigated simultaneously. Results Proband was a 41-year-old Chinese woman who presented syndrome of Fabry disease and TBMN including angiokeratomas, chronic pain, tinnitus, vertigo, left ventricular hypertrophy and nephropathy as proteinuria, microscopic hematuria and hypertension. A percutaneous renal biopsy was performed on the proband, which was consistent with FSGS and vaculization of podocytes by light microscopy.Electron microscopy showed concentric lamellated inclusions in some podocytes. Diffuse thinning of glomerular basement membrane (GBM) with a mean thickness of (216±31) nm was found. The diagnosis of TBMN with suspected Fabry disease was identified. Family screening showed that her daughter had microscopic hematuria, tinnitus and neuropathic pain. One of her sisters only had microscopic hematuria. The activity of α-galacsidase A (α-Gal A )enzyme in the proband and her daughter was 33 units and 75 units respectively (the normal range is 100 to 500 units). They all carried the novel GLA mutation 1208 ins 21 bp and COL4A3 SNP c: 3627G＞A(p:M1209I). While her sister who only had microscopic hematuria just carried the variant of COL4A3 gene-c:3627G ＞A (p:M1209I), and had the normal activity of α-Gal A with no mutation of GLA.Conclusion TBMN should be considered in the patients of Fabry disease with the condition of benign familial hematuria.