儿童Dent病的临床表型、基因型及预后分析  

Analysis of clinical features, genotype, and prognosis of children with Dent disease

作　　者：杨婧怡 刘小荣[1] Yang Jingyi;Liu Xiaorong(Department of Nephrology,Beijing Children's Hospital,Capital Medical University,National Center for Children's Health,Beijing 100045,China)

机构地区：[1]国家儿童医学中心,首都医科大学附属北京儿童医院肾脏内科,北京100045

出　　处：《中华实用儿科临床杂志》2025年第4期262-267,共6页Chinese Journal of Applied Clinical Pediatrics

基　　金：国家重点研发计划(2022YFC2705101)。

摘　　要：目的总结儿童Dent病的临床表型、基因型特点、治疗现状及预后情况。方法选取2008年1月至2024年6月在首都医科大学附属北京儿童医院肾脏内科住院的15例Dent病患儿进行回顾性病例系列分析,根据突变基因不同,Dent病患儿分为2组:Dent病Ⅰ型和Dent病Ⅱ型,总结临床表型、基因型特点以及治疗和预后,采用t检验或Wilcoxon秩和检验对疾病治疗效果进行分析。结果15例患儿均为男童,平均起病年龄为4.45岁。患儿均为隐匿起病,可同时合并肾结石/肾钙质沉着(66.7%)、身材矮小症(46.7%)、佝偻病(20.0%)等表现。2组尿蛋白及尿钙无明显差异,但Ⅰ型临床表现较Ⅱ型重。肾脏活检结果提示病变均同时累及肾小管及肾小球。患儿可存在系膜增生、小球硬化,部分合并球囊粘连、足细胞足突融合及新月体。15例患儿中,11例为CLCN5基因变异,4例为OCRL基因变异,有5个突变位点为新报道。截至随访结束时,治疗后24h尿钙[0.26(0.22,0.36)mmol/(kg·d)比(0.12±0.05)mmol/(kg·d),P<0.001]、尿钙/尿肌酐[(0.36±0.16)mg/mg比(0.26±0.13)mg/mg,P=0.043]、24h尿蛋白定量[74.34(65.63,79.26)mg/(kg·d)比59.88(56.77,64.23)mg/(kg·d),P=0.002]及尿β2微球蛋白/尿肌酐[33.85(12.26,43.37)mg/mg比(10.47±7.55)mg/mg,P=0.001]较治疗前显著下降,但尿蛋白/尿肌酐、尿α1微球蛋白/尿肌酐无变化。随访过程中,2例Dent病Ⅰ型患儿肾功能进行性下降,分别进展至慢性肾脏病(CKD)3期和5期。结论Dent病可同时累及肾小管及肾小球,Dent病Ⅰ型临床表现相对较重。Dent病以CLCN5基因突变为主。全外显子基因检测是有效的确诊手段,有助于早期诊断、分型,早期干预。目前该病尚无特效治疗,对症治疗可减轻尿钙、尿蛋白,纠正电解质紊乱,但可能无法阻止肾功能进一步恶化。大部分患儿肾功能尚正常,预后良好,少部分进展至CKD。Objective:To summarize clinical and genotypic features,treatment,and prognosis of children with Dent disease.Methods:A retrospective case-series study was conducted on 15 children with Dent disease at the Nephrology Department of Beijing Children′s Hospital,Capital Medical University from January 2008 to June 2024.The patients were divided into a typeⅠDent disease group and a typeⅡDent disease group according to the type of mutated genes.The clinical and genotypic characteristics,treatment,and prognosis were described.Then,the treatment effect of the disease was analyzed using the t-test or Wilcoxon rank-sum test.Results:All 15 children were boys,and the average onset age was 4.45 years.The illness struck each child insidiously at first,and it was complicated by nephrolithiasis/nephrocalcinosis(66.7%),short stature(46.7%),and rickets(20.0%).There was no significant difference in urine protein or calcium levels between the 2 groups.However,the typeⅠDent group had more severe clinical symptoms than the typeⅡDent group.Renal biopsy results indicated that lesions affected both tubules and glomeruli.The children were diagnosed with thylakoid hyperplasia,glomerulosclerosis,and in certain cases,glomerular adhesions,pedunculated fusions,and crescents.Of the 15 children,11 had CLCN5 gene variations,and 4 had OCRL gene variations.Five mutants found in this study were reported for the first time.Up to the end of the follow-up,24-hour urinary calcium[0.26(0.22,0.36)mmol/(kg·d)vs.(0.12±0.05)mmol/(kg·d),P<0.001],Ratio of urine calcium to creatinine[(0.36±0.16)mg/mg vs.(0.26±0.13)mg/mg,P=0.043],24-hour urinary protein[74.34(65.63,79.26)mg/(kg·d)vs.59.88(56.77,64.23)mg/(kg·d),P=0.002],and urinaryβ2-microglobulin/creatinine levels[33.85(12.26,43.37)vs.(10.47±7.55)mg/mg,P=0.001]after treatment were significantly lower than those before treatment.The differences in urinary protein/creatinine and urinaryα1-microglobulin/creatinine levels were not significant before and after treatment.Two children in the typeⅠD

关 键 词：儿童 Dent病 CLCN5基因 OCRL基因 低分子量蛋白尿 

分 类 号：R726.9[医药卫生—儿科]