ESPE Abstracts

Background: Single gene variants that give rise to neonatal diabetes mellitus (NDM), maturity onset diabetes of the young (MODY) and syndromic forms of diabetes mellitus (SDM) are responsible for 3.1-4.2% of all diabetes cases. Next generation sequencing techniques (NGS) are the game changer in terms of accurate diagnosis of monogenic diabetes (MD) which in turn allows the most appropriate treatment and the more precise prognostics. This single-center study with relatively larger sample size aimed to evaluate the clinical and genetic characteristics of Chinese children with suspected MD using NGS methods.

Materials and Methods: Data were collected from 1550 consecutive children diagnosed with diabetes or hyperglycemia at the Endocrinology Department of Children’s Hospital of Nanjing Medical University from 2012 to 2023. The genotype and phenotype of 138 children with suspected MD were retrospectively analyzed.

Results: Among the 138 children, 16, 97, and 25 patients with NDM, suspected MODY and SDM were assessed by NGS based panel or whole exome sequencing (WES), with a pick-up rate of 87.5%, 57.8%, and 56%, respectively. In total, there was a high pick-up rate of MD, with 58% (80 of 138) among pediatric patients who were antibody negative. Pathogenic variants were found in GCK, HNF1A, INS, KCNJ11, INSR, HNF4A, ABCC8, WFS1, ALMS1, HNF1B, BLK and ZFP57 genes with 16 novel variants. Additionally, paternal duplication of 6q24 in a patient with PNDM, deletion syndromes of 16p11.2, 17q12 and 7q22 were also identified. In this cohort, GCK- MODY was the leading cause and the mildest type of MODY. GCK -MODY displayed favorable lipid profile when compared to non-GCK-MODY and MODYX, which might be cardioprotective. Following an accurate genetic diagnosis of diabetes, 19 patients switched from insulin therapy to oral agents or lifestyle interventions.

Conclusion: NGS tests helped to identify the precise etiology of monogenic diabetic patients which has implications for better individualized management.