The Center of Endocrinology, Metabolism, Genetics, and Molecular Therapy, Vietnam National Children's Hospital, Hanoi, Vietnam.
Pediatric Department, Hanoi Medical University, Hanoi, Vietnam.
Front Endocrinol (Lausanne). 2022 Apr 19;13:866573. doi: 10.3389/fendo.2022.866573. eCollection 2022.
Neonatal diabetes mellitus (NDM) is a rare (1:90,000 newborns) but potentially devastating metabolic disorder characterized by hyperglycemia combined with low levels of insulin. Dominantly-acting insulin () gene mutations cause permanent NDM through single amino acid changes in the protein sequence leading to protein misfolding, which is retained within the endoplasmic reticulum (ER), causing ER stress and β-cell apoptosis. Over 90 dominantly-acting gene mutations have been identified in individuals with permanent NDM.
The study included 70 infants diagnosed with NDM in the first year of life between May 2008 and May 2021 at the Vietnam National Children's Hospital. Sequencing analysis of all the genes known to cause NDM was performed at the Exeter Genomic Laboratory, UK. Clinical characteristics, molecular genetics, and annual data relating to glycemic control (HbA1c) and severe hypoglycemia of those with mutations were collected. The main outcomes of interest were HbA1c, daily insulin dose, growth, and cognitive/motor development.
Fifty-five of 70 infants (78.5%) with NDM harbored a mutation in a known disease-causing gene and of these, 10 had six different heterozygous mutations. Mean gestational age was 38.1 ± 2.5 weeks and mean birth weight was 2.8 ± 0.5 g. They presented with NDM at 20 ± 17 weeks of age; 6/10 had diabetic ketoacidosis with pH 7.13 ± 0.26; plasma glucose level 32.6 ± 14.3 mmol/l and HbA1C 81 ± 15% mmol/mol. After 5.5 ± 4.8 years of insulin treatment, 9/10 have normal development with a developmental quotient of 80-100% and HbA1C 64 ± 7.3 mmol/mol, 9/10 have normal height, weight, and BMI on follow-up.
We report a series of Vietnamese NDM cases with dominant mutations. mutations are the third commonest cause of permanent NDM. We recommend screening of the gene in all children diagnosed with diabetes in the first year of life.
新生儿糖尿病（NDM）是一种罕见的（每 90000 名新生儿中就有 1 例）但可能具有破坏性的代谢疾病，其特征是高血糖合并胰岛素水平低。显性作用的胰岛素（）基因突变通过导致蛋白质错误折叠的蛋白质序列中的单个氨基酸变化导致永久性 NDM，这种错误折叠保留在内质网（ER）中，导致 ER 应激和β细胞凋亡。在患有永久性 NDM 的个体中已鉴定出超过 90 种显性作用的 基因突变。
这项研究纳入了 2008 年 5 月至 2021 年 5 月期间在越南国家儿童医院确诊为 NDM 的 70 名婴儿，这些婴儿在出生后的第一年就被诊断为 NDM。在英国埃克塞特基因组实验室对所有已知导致 NDM 的基因进行了测序分析。收集了携带 基因突变者的临床特征、分子遗传学和与血糖控制（HbA1c）和严重低血糖相关的年度数据。主要观察结果是 HbA1c、每日胰岛素剂量、生长和认知/运动发育。
70 名患有 NDM 的婴儿中有 55 名（78.5%）携带已知致病基因的突变，其中 10 名携带 6 种不同的 杂合 突变。平均胎龄为 38.1±2.5 周，平均出生体重为 2.8±0.5 克。他们在 20±17 周时出现 NDM；10 例中有 6 例伴有糖尿病酮症酸中毒，pH 值为 7.13±0.26；血浆葡萄糖水平为 32.6±14.3mmol/L，HbA1C 为 81±15%mmol/mol。在接受 5.5±4.8 年胰岛素治疗后，10 例中有 9 例发育正常，发育商为 80-100%，HbA1C 为 64±7.3mmol/mol，随访时 10 例中有 9 例身高、体重和 BMI 正常。
我们报告了一系列越南 NDM 病例，这些病例带有显性 突变。 突变是永久性 NDM 的第三大常见病因。我们建议对在出生后第一年被诊断为糖尿病的所有儿童进行 基因筛查。
