一例GATA6基因变异引起儿童特殊类型糖尿病的临床特点及基因变异分析  

Clinical characteristics and genetic analysis of a child with specific type of diabetes mellitus caused by missense mutation of GATA6 gene

作　　者：应令雯 丁宇[1] 李娟[1] 张倩文 常国营[1,2] 郁婷婷[3] 王剑[4] 祝忠群[5] 王秀敏[1,2] YING Lingwen;DING Yu;LI Juan;ZHANG Qianwen;CHANG Guoying;YU Tingting;WANG Jian;ZHU Zhongqun;WANG Xiumin(Department of Endocrinology and Metabolism,Shanghai Children’s Medical Center,Shanghai Jiao Tong University School of Medicine,Shanghai 200127,China;Clinical Research Ward,Shanghai Children’s Medical Center,Shanghai Jiao Tong University School of Medicine,Shanghai 200127,China;Department of Medical Genetics and Molecular Diagnostic Laboratory,Shanghai Children’s Medical Center,Shanghai Jiao Tong University School of Medicine,Shanghai 200127,China;Central Laboratory,International Peace Maternity and Child Health Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200030,China;Department of Cardiothoracic Surgery,Shanghai Children’s Medical Center,Shanghai Jiao Tong University School of Medicine,Shanghai 200127,China)

机构地区：[1]上海交通大学医学院附属上海儿童医学中心内分泌代谢科,上海200127 [2]上海交通大学医学院附属上海儿童医学中心临床研究病区,上海200127 [3]上海交通大学医学院附属上海儿童医学中心遗传分子诊断科,上海200127 [4]上海交通大学医学院附属国际和平妇幼保健院中心实验室,上海200030 [5]上海交通大学医学院附属上海儿童医学中心心胸外科,上海200127

出　　处：《浙江大学学报（医学版）》2023年第6期732-737,共6页Journal of Zhejiang University(Medical Sciences)

基　　金：国家自然科学基金(81900722,82170910)。

摘　　要：一例男性患儿,2岁,2018年11月30日因“多饮、多食、多尿伴血糖升高两周余”就诊于上海交通大学医学院附属上海儿童医学中心。患儿表现为匀称性矮小[身高81 cm(-2.2标准差),体重9.8 kg(-2.1标准差),体重指数14.94 kg/m^(2)(P_(10)~P_(15))],无特殊面容及躯体特征。实验室检查显示,其糖化血红蛋白为14%,空腹C肽为0.3 ng/mL,胰岛自身抗体阴性。口服葡萄糖耐量试验结果提示,空腹和负荷后血糖显著升高,但仍有部分胰岛功能留存(负荷后C肽较基线升高1.43倍)。基因测序提示患儿存在GATA6基因c.1366C>T(p.R456C)杂合变异,确诊为特殊类型糖尿病。该患儿既往有先天性心脏病,11月龄时先天性心脏病术后出现一过性高渗性高血糖状态。患儿确诊后采取胰岛素替代治疗,但不规则随访,最近随访距离确诊糖尿病约3.5年(患儿5岁11个月),患儿空腹血糖6.0~10.0 mmol/L,餐后2 h血糖多数17.0~20.0 mmol/L。A 2-year-old boy was admitted to Shanghai Children’s Medical Center,Shanghai Jiao Tong University School of Medicine in Nov 30th,2018,due to polydipsia,polyphagia,polyuria accompanied with increased glucose levels for more than 2 weeks.He presented with symmetrical short stature[height 81 cm(-2.2 SD),weight 9.8 kg(-2.1 SD),body mass index 14.94 kg/m^(2)(P_(10)-P_(15))],and with no special facial or physical features.Laboratory results showed that the glycated hemoglobin A1c was 14%,the fasting C-peptide was 0.3 ng/mL,and the islet autoantibodies were all negative.Oral glucose tolerance test showed significant increases in both fasting and postprandial glucose,but partial islet functions remained(post-load C-peptide increased 1.43 times compared to baseline).A heterozygous variant c.1366C>T(p.R456C)was detected in GATA6 gene,thereby the boy was diagnosed with a specific type of diabetes mellitus.The boy had congenital heart disease and suffered from transient hyperosmolar hyperglycemia after a patent ductus arteriosus surgery at 11 months of age.Insulin replacement therapy was prescribed,but without regular follow-up thereafter.The latest follow-up was about 3.5 years after the diagnosis of diabetes when the child was 5 years and 11 months old,with the fasting blood glucose of 6.0-10.0 mmol/L,and the 2 h postprandial glucose of 17.0-20.0 mmol/L.

关 键 词：GATA6转录因子 错义突变 特殊类型糖尿病 先天性心脏病 高渗性高血糖状态 病例报告 

分 类 号：R722.11[医药卫生—儿科] R725.8[医药卫生—临床医学]