中国西南地区儿童Alport综合征临床及病理特点

Clinical and pathological features of children with Alport syndrome in southwest of China

目的:分析中国西南地区儿童Alport综合征(Alport syndrome,AS)临床及病理特点。方法:回顾性分析中国西南地区20例AS患儿病例资料,采用间接免疫荧光法检测Ⅳ型胶原α链在患儿肾脏、皮肤组织的表达,并比较不同临床表型的AS患儿的临床及病理特征。结果:该组患儿以血尿合并蛋白尿为最常见首发症状,首发症状为孤立蛋白尿的患儿24 h尿蛋白水平较血尿合并蛋白尿者高(H=11.959,P=0.003)。有蛋白尿的患儿其家族中尿毒症患者的比例(6/16)较血尿表现者多(1/4)。光镜病理改变以轻中度系膜增生性肾小球肾炎(70.00%)多见,不同临床表型的AS患儿其病理类型分布无统计学差异(χ2=4.149,P=0.900),60.00%的AS存在间质细胞泡沫样,其尿蛋白水平明显高于无间质泡沫样改变者(T=-2.083,P=0.039)。肾脏α5(Ⅳ型)链免疫荧光结果分析,15例(75.00%)为X性连锁显性遗传性AS(X-linked dominant inherited Alport syndrome,XLAS),余5例尚不能根据α5(Ⅳ型)链的缺失判断其遗传类型。2例患儿同时行皮肤基底膜α5(Ⅳ型)链检测,结果与肾脏检测一致。结论:中国西南地区儿童AS血尿合并蛋白尿是最常见首发症状,主要遗传方式为XLAS(75.00%)。不同临床表型的AS患儿其病理类型分布无统计学差异,但蛋白尿越重,其肾小管间质泡沫样改变越重。皮肤活检诊断XLAS与肾脏检测结果一致,必要时可替代肾活检,对家系调查筛选携带者及遗传咨询具有重要意义。

Objective：To analyze the clinical and pathological features of children with Alport syndrome （AS） in southwest of China. Methods ： Totally 20 patients with AS in southwest China were retrospectively reviewed and the clinical data were collected. The distribution of type Ⅳ collagen α chain in renal and skin tissues was detected by indirect immunofluorescence assay. Clinical and pathological features of children with AS were compared among different clinical phenotypes as well. Results ： Most children showed microscopic hematuria associated with proteinuria as initial symptom. The 24 h urinary protein level was higher in patients with isolated proteinuria than in those with hematuria and proteinuria（H=1 1.959,P=0.003）. The proportion of uremic patients in the family of children with proteinuria was （6/16） higher than that in the family of children with hematuria （1/4）. The findings by light microscope mostly revealed mild to moderate mesangial proliferative glomerulonephritis（70.00%）. There was no significant difference in pathological type distribution among AS children with variable clinical phenotypes（χ2=4.149,P=0.900）. About 60% patients with AS had foam cells in kidney intemtitium ,whose urine protein level was significantly higher than those without foam cells（ T=-2.083 ,P=0.039）. Based on different AS genotypes＇ immunofluorescence characteristics of type IV collagen （x5 chains in base membrane, 15 patients （75%） were diagnosed as X-linked dominant inherited AS（XLAS） and 5 patients did not determine the inherited types yet according to the deletion of type IV collagen α5 chains. Two children with AS also detected collagen type Ⅳ α5 chains in epithelial basement membrane and the results were the same as detecting type IV collagen α5 chains in glomerular basement membrane. Conclusion：In southwest China,hematuria associated with proteinuria is the main initial clinical manifestation in children with AS. The main inheriting type is XLAS（75%）. There was no significant difference in AS children with variable clinical phenotypes,however,the higher the level of proteinuria, the more severe the change in renal tubular interstitial. The diagnosis of XLAS by skin biopsy is consistent with that by renal biopsy and skin biopsy can replace renal biopsy under certain circumstances. Moreover,skin biopsy plays an important role in screening the carriers and making genetic counseling.