Ukrainian Scientific and Practical Center of Endocrine Surgery, Transplantation of Endocrine Organs and Tissues of the Ministry of Health of Ukraine, Kyiv, Ukraine.
Institute of Biomedical and Clinical Science, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK.
Diabet Med. 2023 May;40(5):e15013. doi: 10.1111/dme.15013. Epub 2022 Dec 15.
The aim of this study is to elucidate the aetiology and clinical features of neonatal and early-onset diabetes in a large database for pediatric diabetes patients in Ukraine.
We established a Pediatric Diabetes Register to identify patients diagnosed with diabetes before 9 months of age. Genetic testing was undertaken for 66 patients from 65 unrelated families with diabetes diagnosed within the first 6 months of life (neonatal diabetes, n = 36) or between 6 and 9 months (early-onset diabetes, n = 30).
We determined the genetic aetiology in 86.1% of patients (31/36) diagnosed before 6 months and in 20% (6/30) diagnosed between 6 and 9 months. Fourteen individuals (37.8% of those with a genetic cause identified) had activating heterozygous variants in ABCC8 or KCNJ11. An additional 10 individuals had pathogenic variants in the INS or GCK genes, while 4 had 6q24 transient neonatal diabetes. Rare genetic subtypes (including pathogenic variants in EIF2AK3, GLIS3, INSR, PDX1, LRBA, RFX6 and FOXP3) were identified in nine probands (24.3% of solved cases), 6 of whom died. In total, eight individuals died between infancy and childhood, all of them were diagnosed before 6 months and had received a genetic diagnosis.
In the last decade, the increased availability of comprehensive genetic testing has resulted in increased recognition of the contribution of rare genetic subtypes within pediatric diabetes cohorts. In our study, we identified a high mortality rate among these patients.
本研究旨在阐明乌克兰大型儿科糖尿病患者数据库中新生儿和早发糖尿病的病因和临床特征。
我们建立了一个儿科糖尿病登记处，以确定在 9 个月龄前被诊断为糖尿病的患者。对 65 个无关家族的 66 名糖尿病患者（6 个月内确诊的为新生儿糖尿病，n=36；6-9 个月内确诊的为早发糖尿病，n=30）进行了基因检测。
我们在 6 个月前确诊的 36 例患者中确定了 86.1%（31/36）的遗传病因，在 6-9 个月间确诊的 30 例患者中确定了 20%（6/30）的遗传病因。14 名患者（确定遗传病因的患者中 37.8%）存在 ABCC8 或 KCNJ11 的激活杂合变异。另有 10 名患者 INS 或 GCK 基因存在致病性变异，4 名患者存在 6q24 短暂性新生儿糖尿病。9 名先证者（已解决病例的 24.3%）存在罕见的遗传亚型（包括 EIF2AK3、GLIS3、INSR、PDX1、LRBA、RFX6 和 FOXP3 中的致病性变异），其中 6 名死亡。总的来说，有 8 名患者在婴儿期和儿童期死亡，他们均在 6 个月前被诊断，且进行了基因诊断。
在过去十年中，综合基因检测的普及程度不断提高，这导致儿科糖尿病患者群体中罕见遗传亚型的识别率不断增加。在我们的研究中，我们发现这些患者的死亡率较高。
