Supplementary Material for: Clinical Characteristics, Molecular Features, and Long-Term Follow-Up of 15 Patients with Neonatal Diabetes: A Single-Centre Experience

Background: Diabetes diagnosed within the first 6 months of life is defined as neonatal diabetes mellitus (NDM). Mutations in the KCNJ11, ABCC8, and INS genes are the most common cause of permanent NDM. In populations with a high rate of consanguinity, Wolcott-Rallison syndrome caused by biallelic EIF2AK3 mutations is common. Methods: We studied the clinical characteristics and underlying genetic cause of disease in 15 individuals with diabetes onset before 6 months of age as defined by sustained hyperglycaemia requiring insulin treatment. Patients who had a remission of the diabetes, defined by a normal blood glucose and HbA1c value without insulin or sulphonylurea (SU) treatment, within the first 18 months of life were classified as having transient NDM (TNDM). Results: We report 15 patients with NDM from 14 unrelated families, including 10 with reported parental consanguinity. 1/15 patients had a remission of diabetes, leading to a diagnosis of TNDM. Mutations were detected in 80% (n = 12/15) of the cohort (ABCC8 [n = 4], PTF1A-distal enhancer [n = 3], KCNJ11 [n = 2], EIF2AK3 [n = 1], INS [n = 1], and SLC19A2 [n = 1]). All cases were initially treated with multiple dose insulin injections. One patient with an ABCC8 mutation transitioned from insulin to SU resulting in improved metabolic control at the age of 20 years. Conclusion: Although the number of individuals born to consanguineous parents was considerably high in this cohort, KATP channel mutations (ABCC8/KCNJ11) were more common than EIF2AK3 mutations (n = 6 vs. n = 1). Genetic analyses should be performed in all NDM cases due to the potential impact on treatment and prognosis.背景：出生后6个月内确诊的糖尿病被定义为新生儿糖尿病（neonatal diabetes mellitus, NDM）。KCNJ11、ABCC8及INS基因的突变是永久性新生儿糖尿病最常见的致病原因。在近亲婚配率较高的人群中，由双等位EIF2AK3突变导致的Wolcott-Rallison综合征较为常见。 方法：本研究纳入15例发病于出生后6个月内的糖尿病患者，其诊断标准为持续高血糖且需接受胰岛素治疗，我们对这些患者的临床特征及潜在致病遗传学原因进行了分析。若患者在出生后18个月内实现糖尿病缓解——即血糖及糖化血红蛋白（HbA1c）水平正常且无需胰岛素或磺脲类（sulphonylurea, SU）药物治疗，则被归类为暂时性新生儿糖尿病（transient NDM, TNDM）。 结果：本研究纳入来自14个无亲缘关系家系的15例新生儿糖尿病患者，其中10例存在父母近亲婚配史。15例患者中1例实现糖尿病缓解，最终确诊为暂时性新生儿糖尿病。本队列中80%（n=12/15）的患者检测到致病突变，分别为ABCC8突变（n=4）、PTF1A远端增强子突变（n=3）、KCNJ11突变（n=2）、EIF2AK3突变（n=1）、INS突变（n=1）及SLC19A2突变（n=1）。所有患者初始均接受多次胰岛素注射治疗。1例携带ABCC8突变的患者在20岁时从胰岛素治疗转换为磺脲类药物治疗，代谢控制情况得到改善。 结论：尽管本队列中父母为近亲婚配的患者比例较高，但KATP通道相关突变（ABCC8/KCNJ11）的检出率仍高于EIF2AK3突变（n=6 vs n=1）。鉴于遗传学检测对治疗方案及预后的潜在影响，所有新生儿糖尿病患者均应进行遗传学分析。