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

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2023 Dec 13;52(6):732-737. doi: 10.3724/zdxbyxb-2023-0351.
[Article in English, Chinese]

Abstract
in English, Chinese

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/m2 (P10-P15)], 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.

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/m2（P10~P15）］，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。.

Keywords: Case report; Congenital heart disease; GATA6 transcription factor; Hyperosmolar hyperglycemic state; Missense mutation; Specific types of diabetes.

Publication types

  • Case Reports

MeSH terms

  • Blood Glucose
  • C-Peptide / genetics
  • Child
  • Child, Preschool
  • China
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / genetics
  • GATA6 Transcription Factor / genetics
  • Glucose
  • Humans
  • Infant
  • Insulin / genetics
  • Male
  • Mutation, Missense

Substances

  • C-Peptide
  • Insulin
  • Glucose
  • Blood Glucose
  • GATA6 protein, human
  • GATA6 Transcription Factor