[Hyperglycemia caused by mutation of GCK gene in 10 patients analysis of clinical and mutation characteristics].

Objective: To explore the gene mutation characteristics and detailed clinical presentations of hyperglycemia caused by GCK mutations in 10 patients. Methods: The clinical and follow-up data of 10 patients with hyperglycemia caused by mutation of GCK gene were reviewed. The patients were ascertained between January 1, 2014 and August 31, 2018 at the Department of Pediatrics, the First Affiliated Hospital of Zhejiang University and Ningbo Women & Children's Hospital. Clinical data were collected, including age, gender, main complaint, family history, fasting blood glucose, fasting blood insulin, 2-hour blood glucose, 2-hour blood insulin after oral glucose tolerance test, glycosylated hemoglobin, anti-glutamic acid decarboxylase antibody and body mass index. Mutations of GCK gene were detected by Sanger sequencing or high-throughput sequencing of diabetes-related genes in the patients and their family members. Results: There were ten patients, 8 of them were male, 2 were female.The ages at diagnosis varied between 4.7 to 12.3 years. The patients usually did not have obvious clinical symptoms of diabetes mellitus. Most of them were unexpectedly found to have hyperglycemia and with impaired glucose metabolism in three consecutive generations. The fasting blood glucose of patients was 6.8-7.7 mmol/L, 2-hour postprandial blood glucose was 7.8-11.6 mmol/L. Fasting blood insulin was 0.5-8.5 mU/L, glucose tolerance test results showed that 2 h postprondial blood insulin was 1.3-55.4 mU/L. The level of glycosylated hemoglobin was 6.1%-6.8%. Anti-glutamic acid decarboxylase antibody was negative in all patients. The GCK mutations identified in patients and one of their parents were located at exon5 (4 cases), exon9 (2 cases), exon2 (1 case), exon4 (1 case), exon6 (1 case) and exon7 (1 case). Conclusions: Most of the hyperglycemia patients caused by GCK mutations did not have typical clinical symptoms of diabetes. The fasting blood glucose was slightly elevated. Abnormal glucose tolerance test results were found in all 10 patients. Three consecutive generations of family had impaired glucose metabolism. GCK mutations located at exon 5 were common in 10 cases. There was no correlation between type of mutations and plasma glucose levels in domestic and international researches. When fasting glucose was found abnormal in clinic, a complete family history should be taken and the GCK gene should be sequenced to confirm the diagnosis in time.目的： 分析总结10例葡萄糖激酶（GCK）基因变异导致的高血糖的临床特征及变异特点。 方法： 回顾性分析浙江大学医学院附属第一医院儿科、宁波市妇女儿童医院内分泌科2014年1月1日至2018年8月31日10例基因检测明确为GCK基因变异导致高血糖患儿的临床资料，进行家系调查并取得家系成员外周血基因组DNA行GCK基因变异位点一代Sanger测序。 结果： 10例患儿中男8例，女2例，诊断年龄范围为4.7~12.3岁，均无明显临床症状，大部分为"意外"发现血糖升高进而检查被诊断，家族中连续三代均有糖代谢异常患者。患儿空腹血糖为6.8~7.7 mmol/L，餐后2 h血糖为7.8~11.6 mmol/L，空腹血胰岛素为0.5~8.5 mU/L，餐后2 h胰岛素为1.3~55.4 mU/L，血糖化血红蛋白为6.1%~6.8%，抗谷氨酸脱羧酶抗体均阴性。患儿和其父母其中一方的GCK基因变异发生在外显子5有4例，外显子9有2例，外显子2、4、6、7各1例。 结论： GCK基因变异导致的高血糖患儿常无糖尿病典型症状，多表现为空腹血糖增高，糖耐量试验均有异常，家族中连续三代有糖代谢异常者。本研究10例患儿GCK基因变异多发生在外显子5，国内外研究尚未发现血糖水平与变异位点有明确相关性。临床上对空腹血糖异常者，需仔细询问家族史，必要时行GCK基因检测以明确诊断。.