High prevalence of maturity‐onset diabetes of the young in the Czech Republic: A 25‐year nationwide registry‐based study

AIMS: Maturity-Onset Diabetes of the Young (MODY) results from a single-gene defect. This study aimed to determine the minimal prevalence, screening indicators, as well as clinical characteristics of MODY in the Czech Republic based on data from 25 years of the nationwide registry. METHODS: Clinical and genetic data were collected from individuals suspected of having MODY referred for genetic testing and registered in the National Registry for Monogenic Diabetes between 1999 and 2023. Prevalence estimates were calculated using Czech national census data. The cluster analyses of probands with the absence of a detected monogenic cause of diabetes were performed with the Mclust library. RESULTS: In total, 1879 probands with suspected MODY were registered, and 728 (39%) received a confirmed diagnosis (in total, 1473 individuals). GCK, HNF1A and HNF4A gene variants accounted for 93% of all diagnoses. The average prevalence of MODY was 136 per million inhabitants, peaking at 240 per million in the northeast region of the country. If the highest recorded minimum prevalence is applied to the total population in the Czech Republic, approximately 44% of cases remain undiagnosed. A cluster statistical analysis identified five overlapping, clinically defined subgroups within the probands with no identified monogenic cause of diabetes. CONCLUSIONS: This study provides one of the highest national prevalence rates of MODY to date. Nevertheless, approximately half of the expected cases remain undetected. The negative group included several different subtypes of glucose tolerance disorders, which should guide future research into the pathogenesis of different types of diabetes.