CLCNKA和CLCNKB基因突变致婴儿巴特综合征1例报告及文献分析

A case report and literature analysis of an infant with Batter syndrome caused by CLCNKA and CLCNKB gene mutation

巴特综合征(Bartter syndrome, BS)是由遗传基因突变或缺失引起的一种伴有电解质和内分泌紊乱的遗传代谢疾病,临床表现为呕吐、便秘、喂养困难、体重不增、生长发育迟缓等,实验室检查存在低钾血症、代谢性碱中毒、高肾素血症、醛固酮增多症等。BS属于常染色体隐性遗传病,发病率极低,所以诊断及治疗较为困难。近年来,随着基因检测等技术的进步,我国对BS的研究已取得了长足进步,越来越多的BS得以精准诊断。按照已知基因突变类型可将其可分为1型、2型、3型、4型、5型及Gitelman综合征,共6种类型,其中4型又分4a型及4b型。目前临床上的BS患儿以3型即经典型BS最常见。本文报告1例4b型巴特综合征(Bartter syndrome type 4b, BS4b)患儿,经过2次3人家系基因测序,发现患儿除Alport综合征外,还存在双等位基因CLCNKA和CLCNKB共同变异,患儿父母均为该类型基因缺陷携带者。患儿最终诊断为BS4b、Alport综合征,结合其患者特点、诊治经过等临床资料以及相关文献分析,以期为认识及诊治该病提供经验。

Bartter syndrome(BS)is a kind of inherited metabolic disease characterized by electrolyte and endocrine disorder,resulting from genetic gene mutation or deletion.Clinically,it manifests as vomiting,constipation,feeding difficulties,weight loss,growth retardation.The laboratory examination shows hypokalemia,metabolic alkalosis,hyperreninemia,aldosteronism,etc.As an autosomal recessive genetic disease,BS has an extremely low incidence rate,making diagnosis and treatment quite challenging.In recent years,with the progress of gene detection and other technologies,China has made great progress in the study of BS,more and more BS has been diagnosed accurately.According to known gene mutation types,it can be divided into type 1,type 2,type 3,type 4,type 5 and Gitelman syndrome,a total of 6 types,with type 4 further divided into type 4a and type 4b.At present,the most common type of children with BS in clinical practice is type 3,which is the classic type of BS.This paper reports a case of Bartter syndrome type 4b(BS4b).After two rounds of three-generation family gene sequencing,it was discovered that the infant had a combined mutation of both the CLCNKA and CLCNKB alleles,in addition to Alport syndrome,and both parents were carriers of this type of gene defect.The child was finally diagnosed as BS4b and Alport syndrome.This report,combined with the patient′s clinical features,diagnosis and treatment process,as well as related literature analysis,aims to provide experience for understanding and diagnosis and treatment of this disease.