Chandran Suresh, Rajadurai Victor Samuel, Hoi Wai Han, Flanagan Sarah E, Hussain Khalid, Yap Fabian
Division of Medicine, KK Women's and Children's Hospital, Singapore, Singapore.
Duke-NUS Medical School, National University of Singapore, Singapore, Singapore.
Front Pediatr. 2020 Jun 26;8:320. doi: 10.3389/fped.2020.00320. eCollection 2020.
Maturity-onset diabetes of the young (MODY) classically describes dominantly inherited forms of monogenic diabetes diagnosed before 25 years of age due to pancreatic β-cell dysfunction. In contrast, mutations in certain MODY genes can also present with transient or persistent hyperinsulinemic hypoglycemia in newborn infants, reflecting instead β-cell dysregulation. Of the MODY genes described to date, only hepatocyte nuclear factor-4-alpha (; MODY1) and hepatocyte nuclear factor-1-alpha ; MODY3) mutations may result in a biphasic phenotype of hypoglycemia in early life and hyperglycemia in later life. We report a family with a novel mutation with diverse phenotypic presentations of glucose dysregulation. The proband was a term, appropriate-for-gestational age male infant with symptomatic hypoglycemia on day 3 of life needing high glucose infusion rate to maintain normoglycemia. He was born to a non-obese and non-diabetic mother. Glucose regulation was optimized using diazoxide upon confirmation of hyperinsulinism. Cascade genetic screening identified the same mutation in his father and elder sister, but mother was negative. Father was diagnosed with Type 1 diabetes at 15 years of age that required insulin therapy. Proband's elder sister, born at term appropriate for gestational age, presented with transient neonatal hypoglycemia needing parenteral glucose infusion for a week followed by spontaneous resolution. The paternal grandparents were negative for this mutation, confirming a paternal mutation and autosomal dominant inheritance in this family. This pedigree suggests that the presence of early-onset paternal diabetes should prompt molecular testing in infants presenting in the newborn period with diazoxide-responsive hyperinsulinemic hypoglycemia, even in the absence of maternal diabetes and macrosomia.
青年发病的成年型糖尿病（MODY）传统上指因胰腺β细胞功能障碍在25岁之前诊断出的单基因糖尿病的显性遗传形式。相比之下，某些MODY基因的突变也可在新生儿中表现为短暂性或持续性高胰岛素血症低血糖症，这反而反映了β细胞调节异常。在迄今描述的MODY基因中，只有肝细胞核因子-4-α（MODY1）和肝细胞核因子-1-α（MODY3）突变可能导致早期低血糖和后期高血糖的双相表型。我们报告了一个具有新型突变的家族，其血糖调节异常具有多种表型表现。先证者是一名足月儿，适于胎龄男性婴儿，出生第3天出现有症状的低血糖症，需要高葡萄糖输注速率来维持血糖正常。他的母亲非肥胖且无糖尿病。在确诊高胰岛素血症后，使用二氮嗪优化血糖调节。级联基因筛查在他的父亲和姐姐中发现了相同的突变，但母亲为阴性。父亲在15岁时被诊断为1型糖尿病，需要胰岛素治疗。先证者的姐姐足月出生，适于胎龄，出现短暂性新生儿低血糖症，需要肠外输注葡萄糖一周，随后自行缓解。祖父母对此突变呈阴性，证实该家族中此突变为父系突变且为常染色体显性遗传。这个家系表明，即使不存在母亲糖尿病和巨大儿情况，对于出生时出现对二氮嗪反应性高胰岛素血症低血糖症的婴儿，早发型父系糖尿病的存在也应促使进行分子检测。
