Cao B Y, Miao M, Wang D M, Meng X, Gong C X
Department of Endocrinology, Genetics and Metabolism, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, ChinaMiao Miao is working at the Department of Pediatrics, Beijing Mentougou District Maternal and Child Health Hospital, Beijing 102308, China.
Zhonghua Er Ke Za Zhi. 2024 Jun 2;62(6):530-534. doi: 10.3760/cma.j.cn112140-20231127-00391.
To analyze the genetic and clinical characteristics, treatment and prognosis of patients diagnosed with maturity onset of diabetes of the young (MODY) 12 subtype. This retrospective study collected and analyzed data from 5 children with MODY12 subtype caused by ABCC8 gene variants who underwent inpatient and outpatient genetic testing at Beijing Children's Hospital from January 2016 to December 2023. Their clinical and genetic features, treatment, and follow-up results were analyzed. Among the 5 patients with MODY12 subtype, 4 were male and 1 was female, with an age of 13.4 (5.5, 14.6) years. Four of the patients were born large for gestational age, while one was born small for gestational age. Two patients were overweight or obese. Three patients exhibited typical symptoms of diabetes, while 2 were incidentally found to have elevated blood glucose level. One patient was found to have diabetic ketoacidosis at onset, who was diagnosed with congenital hyperinsulinism during the neonatal period and received diazoxide treatment, and experienced intellectual developmental delay. All 5 patients had autosomal dominant inherited diabetes within 3 generations. The fasting blood glucose at onset was 7.5 (6.5, 10.0) mmol/L, the haemoglobin A1c (HbA1c) was 11.8% (7.5%, 13.5%), and the fasting C-peptide was 1.2 (1.1, 2.2) μg/L. The duration of follow-up was 15 (9, 32) months. One patient underwent lifestyle intervention, 2 received metformin orally, 1 received insulin therapy, and the other received subcutaneous injection of insulin combined with sulfonylurea orally. At the last follow-up, the median fasting blood glucose was 6.1 (5.1, 7.0) mmol/L, the HbA1c was 5.9% (5.7%, 7.1%), and the fasting C-peptide was 1.7 (0.9, 2.9) μg/L. One patient developed diabetic retinopathy. There were 4 missense variations in ABCC8 gene and one in-frame deletion, all of which were maternally inherited heterozygotes. MODY12 subtype is a heterogeneous disorder with the age of onset from infancy to adolescence. It can present as mild hyperglycemia or diabetic ketoacidosis, and has a high incidence of obesity. Definitive diagnosis can be achieved through genetic test, and individualized treatment is recommended based on glucose levels.
分析青少年发病的成年型糖尿病（MODY）12亚型患者的遗传和临床特征、治疗及预后。本回顾性研究收集并分析了2016年1月至2023年12月在北京儿童医院接受住院和门诊基因检测的5例由ABCC8基因变异引起的MODY12亚型患儿的数据。分析了他们的临床和遗传特征、治疗及随访结果。在5例MODY12亚型患者中，男性4例，女性1例，年龄为13.4（5.5，14.6）岁。4例患者出生时为大于胎龄儿，1例为小于胎龄儿。2例患者超重或肥胖。3例患者表现出典型的糖尿病症状，2例偶然发现血糖水平升高。1例患者发病时出现糖尿病酮症酸中毒，新生儿期被诊断为先天性高胰岛素血症并接受二氮嗪治疗，且有智力发育迟缓。所有5例患者三代内均有常染色体显性遗传性糖尿病。发病时空腹血糖为7.5（6.5，10.0）mmol/L，糖化血红蛋白（HbA1c）为11.8%（7.5%，13.5%），空腹C肽为1.2（1.1，2.2）μg/L。随访时间为15（9，32）个月。1例患者接受生活方式干预，2例口服二甲双胍，1例接受胰岛素治疗，另1例接受皮下注射胰岛素联合口服磺脲类药物治疗。末次随访时，空腹血糖中位数为6.1（5.1，7.0）mmol/L，HbA1c为5.9%（5.7%，7.1%），空腹C肽为1.7（0.9，2.9）μg/L。1例患者发生糖尿病视网膜病变。ABCC8基因有4个错义变异和1个框内缺失，均为母系遗传杂合子。MODY12亚型是一种异质性疾病，发病年龄从婴儿期到青春期。可表现为轻度高血糖或糖尿病酮症酸中毒，肥胖发生率高。通过基因检测可明确诊断，建议根据血糖水平进行个体化治疗。
