Beltrand Jacques, Busiah Kanetee, Vaivre-Douret Laurence, Fauret Anne Laure, Berdugo Marianne, Cavé Hélène, Polak Michel
Paediatric Endocrinology, Gynaecology and Diabetology, Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris, IMAGINE Institute, ENDO-European Reference Network Team, Paris, France.
Faculty of Medicine, Université de Paris, Paris, France.
Front Pediatr. 2020 Sep 30;8:540718. doi: 10.3389/fped.2020.540718. eCollection 2020.
Neonatal Diabetes (ND) mellitus is a rare genetic disease (1 in 90,000 live births). It is defined by the presence of severe hyperglycaemia associated with insufficient or no circulating insulin, occurring mainly before 6 months of age and rarely between 6 months and 1 year. Such hyperglycaemia requires either transient treatment with insulin in about half of cases, or permanent insulin treatment. The disease is explained by two major groups of mechanism: malformation of the pancreas with altered insulin-secreting cells development/survival or abnormal function of the existing pancreatic β cell. The most frequent genetic causes of neonatal diabetes mellitus with abnormal β cell function are abnormalities of the 6q24 locus and mutations of the or genes coding for the potassium channel in the pancreatic β cell. Other genes are associated with pancreas malformation or insufficient β cells development or destruction of β cells. Clinically, compared to patients with an or mutation, patients with a 6q24 abnormality have lower birth weight and height, are younger at diagnosis and remission, and have a higher malformation frequency. Patients with an or mutation have neurological and neuropsychological disorders in all those tested carefully. Up to 86% of patients who go into remission have recurrent diabetes when they reach puberty, with no difference due to the genetic origin. All these results reinforce the importance of prolonged follow-up by a multidisciplinary pediatric team, and later doctors specializing in adult medicine. 90% of the patients with an or mutation as well as those with 6q24 anomalies are amenable to a successful switch from insulin injection to oral sulfonylureas.
新生儿糖尿病（ND）是一种罕见的遗传性疾病（每90000例活产中有1例）。它的定义是存在严重高血糖且伴有循环胰岛素不足或缺乏，主要发生在6个月龄之前，6个月至1岁之间较为罕见。这种高血糖在约一半的病例中需要短期胰岛素治疗，或长期胰岛素治疗。该疾病由两大类机制引起：胰腺畸形伴胰岛素分泌细胞发育/存活改变或现有胰腺β细胞功能异常。β细胞功能异常的新生儿糖尿病最常见的遗传原因是6q24位点异常以及胰腺β细胞钾通道编码基因或的突变。其他基因与胰腺畸形、β细胞发育不足或β细胞破坏有关。临床上，与或突变的患者相比，6q24异常的患者出生体重和身高较低，诊断和缓解时年龄较小，畸形发生率较高。在所有经过仔细检测的或突变患者中都存在神经和神经心理障碍。高达86%进入缓解期的患者在青春期时会复发糖尿病，且与遗传起源无关。所有这些结果都强化了多学科儿科团队以及后来的成人医学专科医生进行长期随访的重要性。90%的或突变患者以及6q24异常患者能够成功从胰岛素注射转换为口服磺脲类药物。
