ESPE Abstracts

Background: The incidence rate of maturity onset diabetes of the young (MODY) and the proportion of different types of MODY will be different in different countries and races. GCK, HNF1A, and HNF4A are the three most common types of MODY, but the occurrence of other rare MODY subtypes in Chinese children is unknown. Therefore, studying the case group of MODY in Chinese children can help deepen understanding of MODY, early identification, and precise treatment.

Methods: From January 2015 to December 2022, patients with persistent hyperglycemia who were suspected of having monogenic diabetes or diabetes syndrome were recruited and next-generation sequencing (NGS) was performed at Shanghai Children's Medical Center. Clinical and laboratory characteristics of the patients were recorded. Target panel sequencing and whole-exome sequencing were performed. Candidate variants were verified by Sanger sequencing and other methods as needed. Variant pathogenicity was further evaluated according to the American College of Medical Genetics and Genomics guideline.

Results: A total of 175 children underwent genetic testing. MODY related pathogenic or likely pathogenic gene variants were found among 30 patients. Combined with clinical features, MODY was diagnosed. Among them, 11 patients were diagnosed as GCK-MODY (36.7%), 6 patients were INS-MODY (20%), 5 patients were HNF1A-MODY (16.7%), 5 patients were ABCC8-MODY (16.7%), 2 patients were HNF1B-MODY (6.7%), and 1 patient was HNF4A-MODY (3.3%). There were 2 shift variants, 7 splice site variants, and the rest were missense variants. 7 variants were newly discovered which were not included in databases such as HGMD and gnomAD. 6 patients of INS-MODY were diagnosed as type 1 diabetes for the first time, and diabetes related antibodies were negative in 4 patients. The fluctuation range of glycosylated hemoglobin was 8.3-15.3%, and the fluctuation range of fasting C-peptide level was 0.05-0.67nmol/L in patients with INS-MODY.

Conclusion: GCK-MODY is still the most common type of MODY in Chinese children, while INS-MODY accounts for a relatively high proportion of MODY in Chinese children. Clinical awareness of this type of MODY needs to be improved.