The Jesse Z. and Sara Lea Shafer Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Pediatr Diabetes. 2022 Feb;23(1):45-54. doi: 10.1111/pedi.13295. Epub 2021 Dec 6.
Neonatal diabetes mellitus (NDM) is a rare form of monogenic diabetes, diagnosed before age 6 months. We aimed to describe the clinical characteristics, molecular genetics, and long-term follow-up of NDM patients from a single pediatric endocrine center in Israel.
Retrospective study (1975-2020) of all patients diagnosed with diabetes before 6 months of age, who tested negative for pancreatic autoantibodies. Medical records were reviewed for demographic, familial and medical history, and clinical and biochemical features; a genetic analysis was performed.
Of 24 patients, nine had transient neonatal diabetes (TNDM) and 15 permanent neonatal diabetes (PNDM), of whom five had rare syndromic causes. Genetic etiology was revealed in 87.5% of the NDM cohort, and the most common causes were ABCC8 mutations in TNDM and KCNJ11 and insulin gene mutations in PNDM. The switch from insulin to off-label sulfonylurea therapy was successful for 5/9 (56%) of the qualifying candidates. Severe hypoglycemia and diabetic ketoacidosis developed in 2 (8%) patients, and chronic diabetes complications in 5 (21%) patients with more than 10 years NDM. At last follow-up, weight and height of all but two syndromic PNDM patients were normal. The median height-SDS of the TNDM subgroup was significantly taller and the mean weight-SDS significantly heavier than those of the PNDM subgroup (-0.52 (-0.67, -0.09) vs. -0.9 (-1.42, -0.3) (p = 0.035) and 0.22 ± 0.69 vs. -0.89 ± 1.21 (p = 0.02), respectively). PNDM patients showed no incremental change in mean weight SDS over the time.
The Israeli NDM cohort has clinical and genetic characteristics comparable with other populations. Patients with TNDM were taller and heavier than those diagnosed with PNDM, although both show rapid catch-up growth and reached normal growth parameters. Chronic diabetes complications developed in patients with long-standing NDM.
新生儿糖尿病（NDM）是一种罕见的单基因糖尿病，在 6 个月龄之前被诊断。我们旨在描述以色列单一儿科内分泌中心的 NDM 患者的临床特征、分子遗传学和长期随访结果。
回顾性研究（1975 年至 2020 年）纳入所有在 6 个月龄之前被诊断为糖尿病且胰腺自身抗体检测阴性的患者。我们对患者的人口统计学、家族和病史以及临床和生化特征进行了回顾性分析，并进行了基因分析。
在 24 名患者中，9 名为暂时性新生儿糖尿病（TNDM），15 名为永久性新生儿糖尿病（PNDM），其中 5 名患者存在罕见的综合征病因。NDM 患者中有 87.5%发现了遗传病因，最常见的病因是 TNDM 中的 ABCC8 突变和 PNDM 中的 KCNJ11 和胰岛素基因突变。有 5/9（56%）符合条件的患者成功从胰岛素转为非标签磺脲类药物治疗。2 名（8%）患者出现严重低血糖和糖尿病酮症酸中毒，5 名（21%）患者出现超过 10 年 NDM 的慢性糖尿病并发症。最后一次随访时，除了 2 名综合征性 PNDM 患者外，所有患者的体重和身高均正常。TNDM 亚组的身高 SDS 中位数明显更高，体重 SDS 平均值明显更重，与 PNDM 亚组相比[-0.52（-0.67，-0.09）比-0.9（-1.42，-0.3）（p=0.035）和 0.22±0.69 比-0.89±1.21（p=0.02）]。PNDM 患者的体重 SDS 平均值在随访期间没有增加。
以色列 NDM 队列具有与其他人群相似的临床和遗传特征。与诊断为 PNDM 的患者相比，TNDM 患者更高更重，尽管两者都有快速的追赶性生长，达到了正常的生长参数。长期患有 NDM 的患者发生了慢性糖尿病并发症。
