摘要
目的探讨分型不明的婴幼儿糖尿病的病因。方法回顾分析2013年-2016年收治,3岁内起病的自身抗体阴性胰岛素依赖1型糖尿病(T1DM)患儿的临床资料。结果共收集19例患儿,男12例、女7例,起病年龄8个月~3岁;主要症状为乏力、消瘦、多饮、多尿;糖化血红蛋白8.6%~12%,合并酮症酸中毒14例;19例患儿的胰岛细胞抗体(ICA)、谷氨酸脱羧酶抗体(GAD65-Ab)、胰岛素抗体(IAA)均为阴性,胰岛素水平正常偏低。采用二代测序及甲基化MLPA方法检测28个糖尿病相关基因,2例患儿阳性;其中1例携带HNF1Ac.1699G>A,为已报道的杂合突变,来自其血糖正常的母亲;另1例携带CEL基因的c.2214delT,为尚未见报道的杂合突变,来自其空腹血糖正常的父亲。结论自身抗体阴性T1DM与单基因糖尿病之间存在交叉与重叠,二代测序对早期明确诊断有重要意义。
Objective To explore the etiology of unclassified diabetes mellitus in infancy and early childhood.Methods Clinical data of insulin-dependent type 1 diabetes mellitus(T1DM)patients with pancreatic islet autoantibody-negative with onset age less than 3 years old admitted to our hospital from 2013 to 2016 were retrospectively analyzed.Results A total of 19 patients(12 boys and 7 girls)diagnosed with diabetes mellitus with onset age from on 8 months old to 3 years old.The main symptoms are fatigue,weight loss,polydipsia,and polyuria.HbA1C 8.6%~12%.Fourteen(14)patients were combined with ketoacidosis at diagnosis.Islet cell antibody,glutamate decarboxylase antibody,and insulin antibody were all negative in 19 patients.Insulin levels are normally low.Next-generation sequencing and methylation MLPA technology were used to analyze 28 diabetes mellitus relevant genes.Gene mutations were found in two patients:A c.1699G>A heterozygous mutation in HNF1A gene was identified in patient 1,and Sanger sequencing showed that the mutation was inherited from her mother who’s glucose was normal;a novel heterozygous deletion mutation of c.2214delT in CEL gene was identified in patient 2,and Sanger sequencing showed that the mutation was inherited from the father who’s fasting glucose was normal.Conclusion This study demonstrated genetic overlap between autoantibody negative T1DM and monogenic diabetes.The next-generation sequencing assay has an important significance for helping early diagnosis of DM.
作者
沈凌花
卫海燕
张英娴
陈琼
刘芳
刘晓景
杨海花
崔岩
陈永兴
杨威
SHEN Linghua;WEI Haiyan;ZHANG Yingxian;CHEN Qiong;LIU Fang;LIU Xiaojing;YANG Haihua;CUI Yan;CHEN Yongxing;YANG Wei(Department of Pediatric Endocrine and Genetic Metabolism,Children’s Hospital Affiliated to Zhengzhou University,Henan provincial Children’s hospital,Zhengzhou children’s hospital. Zhengzhou 450000,Henan,China)
出处
《临床儿科杂志》
CAS
CSCD
北大核心
2019年第8期594-597,共4页
Journal of Clinical Pediatrics
基金
河南省科技厅支持项目(NO.142102310139)
关键词
糖尿病
婴幼儿
基因突变
单基因糖尿病
diabetes mellitus
infancy
gene mutation
monogenic diabetes mellitus
