91例儿童Alport综合征临床、病理特点及误诊分析

Clinical and pathological features and the misdiagnosis of childhood Alport syndrome: a retrospective analysis of 91 cases

摘要:

目的 探讨儿童Alport综合征（AS）临床、病理特点和诊治情况，以提高对AS的认识。方法 收集确诊的91例AS患儿临床资料进行回顾性分析。结果 91例患儿均有血尿，86例伴有蛋白尿。61例X连锁显性遗传AS（XL-AS）患儿有阳性家族史。肾活检的82例患儿中74例有轻度或轻-中度系膜增生，48例系膜区少量免疫复合物，53例肾小球基底膜（GBM）有变薄、增厚和撕裂。63例进行了肾组织Ⅳ型胶原α3、α5链免疫荧光检测，确诊AS 58例，其中53例符合XL-AS，5例符合常染色体隐性遗传AS。91例AS患儿中，58例通过肾组织Ⅳ型胶原α3、α5链免疫荧光确诊，21例通过电镜确诊，1例通过皮肤活检确诊；12例基因诊断确诊。发现6个COL4A5基因新突变。45例曾被误诊其他疾病，其中41例接受过激素和/或免疫抑制剂治疗。结论 儿童AS临床表现缺乏特异性，特征性GBM电镜改变仅见于部分患儿，本区域儿童AS误诊误治率仍较高。COL4A5基因新突变比例较高。

Abstract:

Objective To explore the clinical and pathological features and the diagnosis of childhood Alport syndrome (AS). Methods A retrospective analysis was performed on clinical data of 91 children with AS. Results Hematuria was observed in all 91 patients, of whom 86 were accompanied with proteinuria. Sixty-one children with X-Linked AS (XL-AS) had positive family history. Renal biopsy was performed on 82 children. Mild to moderate mesangial proliferation was observed in 74 cases. Small amounts of immune complexes deposits in the glomerular mesangial area were observed in 48 cases. Glomerular basement membrane (GBM) attenuation, thickening and layering were observed in 53 cases by electron microscopy (EM). In 63 cases receiving renal tissue type IV collagen α3 and α5 chain immunofluorescence detection, 58 were diagnosed with AS, including 53 cases of XL-AS and 5 cases of autosomal recessive AS. In 91 cases of AS, 58 were diagnosed as AS by renal tissue type IV collagen α3 and α5 chain immunofluorescence, 21 were diagnosed by EM, one was diagnosed by skin biopsy, and 12 were diagnosed by gene detection. Six novel mutations of COL4A5 gene were found. Forty-five cases were misdiagnosed before the diagnosis of AS. Forty-one of the 45 cases received steroids and/or immunosuppressant therapy. Conclusions The clinical manifestations and pathological changes are not specific in children with AS, resulting in a higher rate of misdiagnosis. Typical lesions of GBM under EM are only observed in a part of patients. There is a high novel mutation rate of COL4A5 in the detected AS children.