目的 对COL4A5基因突变的X连锁遗传的Alport综合征(X-linked Alport syndrome,XLAS)患儿的临床表型及基因突变类型进行分析,探讨XLAS患儿与肾病综合征肾炎型的关系.方法 纳入2016年4月至2023年4月期间在医院经二代测序发现COL4A5基因突变最终确诊为Alport综合征的32例患儿,回顾性分析其临床病理特征与基因突变特点.结果 XLAS患儿平均起病年龄(3.68±2.07)岁,平均确诊年龄(6.56±2.95)岁,以孤立性血尿起病12例(37.5%),以血尿和蛋白尿起病8例(25%),以肾病综合征肾炎型起病12例(37.5%),患儿家族史阳性有11例(34.4%),眼部病变3例(9.37%),耳部病变6例(18.75%),后期随访发现7例(21.87%)患儿已发展为慢性肾脏病(chronic kidney disease,CKD).21例患儿行肾脏组织穿刺活检,电镜表现为基底膜变薄(弥漫性或节段性)13例(61.9%),基底膜厚薄不均8例(38.09%);光镜:局灶节段肾小球硬化(FSGS)2 例(9.52%),系膜增生性肾小球肾炎(Ms PGN)11 例(52.38%),微小病变(MCD)8例(38.09%).基因突变类型分为错义突变12例(37.5%)、剪切位点突9例(28.12%)、无义突变 6 例(18.75%)、缺失突变 3 例(9.37%)、移码突变 2 例(6.25%).遗传突变 22 例(68.75%);自发突变10例(27.02%).结论 XLAS患儿在疾病早期临床表现和病理特征均不典型,进展缓慢,部分患儿早期易误诊为肾病综合征肾炎型,对于疑似本病尽早完善基因检测,合理药物选择,科学预测预后.
Objective To analyze the clinical phenotypes and mutation types of children with X-linked Alport syndrome(XLAS)with mutations in COL4A5 gene,and to explore the relationship between children with XLAS and nephrotic syndrome nephritic type.Methods Thirty-two children with COL4A5 gene mutations detected by second-generation sequencing and finally diagnosed with Alport syndrome at Guangzhou Red Cross Hospital affiliated with Jinan University and the First People's Hospital of Guangzhou between April 2016 and April 2023 were included,and their clinicopathological features and gene mutation characteristics were retrospectively analyzed.Results The mean age of onset of disease in children with XLAS was(3.68±2.07)years old,the mean age at diagnosis(6.56±2.95)years old,12 cases(37.5%)started with isolated hematuria,8 cases(25%)started with hematuria and proteinuria,12 cases(37.5%)started with nephrotic syndrome nephritic phenotype,and the positive family history of the children was found in 11 cases(34.4%),ocular lesions were found in 3 cases(9.37%),ear lesions in 6 cases(18.75%),and 7 cases(21.87%)were found to have developed chronic kidney disease(CKD)in the later follow-up.21 children underwent renal tissue puncture biopsy,and electron microscopy showed thinning of the basement membrane(diffuse or segmental)in 13 cases(61.9%),and uneven thickness of the basement membrane in 8 cases(38.09%);light microscopy showed thinning of the basement membrane in 13 cases(61.9%);light microscopy showed thinning of the basement membrane in 8 cases(38.09%);and light microscopy showed thinning of the basement membrane in 3 cases(11.5%).(38.09%);light microscopy:focal segmental glomerulosclerosis(FSGS)in 2 cases(9.52%),mesangial proliferative glomerulonephritis(Ms PGN)in 11 cases(52.38%),and minimal change disease(MCD)in 8 cases(38.09%).The type of mutation was categorized as missense mutation in 12 cases(37.5%),shear site mutation in 9 cases(28.12%),nonsense mutation in 6 cases(18.75%),deletion mutation in 3 cases(9.37%),and code shift mutation in 2 cases(6.25%).Genetic mutations were present in 22 cases(68.75%);spontaneous mutations were present in 10 cases(27.02%).Conclusions Children with XLAS have atypical clinical manifestations and pathologic features in the early stage of the disease,and the progress is slow,and some of them are easy to be misdiagnosed as nephrotic syndrome nephritis type in the early stage,so it is important to improve the genetic test for this disease as early as possible,and to make reason-able drug choices to predict the prognosis scientifically.