Endocrine Abstracts

JOINT2088

Introduction: Monogenic diabetes (MD) is a rare form of diabetes caused by single-gene defects. Maturity-onset diabetes of the young (MODY) has well-established diagnostic guidelines in children and adolescents, but individuals over 25 are often overlooked despite the importance of molecular diagnosis for personalized treatment and family risk assessment. The “Genetic Diabetes in Lithuania” project identified GCK, HNF1A, and HNF4A as the most common MODY subtypes in Lithuanian patients up to age 25, leading to the integration of targeted genetic sequencing into clinical practice since 2017. This study aimed to analyze genetic sequencing results from a targeted MD gene panel in patients with non-autoimmune diabetes at our diabetes center from 2017 to 2022.

Methods: We analyzed data of 51 patient (females n = 31 (60, 8%)) who had confirmed MODY diagnosis after targeted sequencing. The total number of patients suspected of MODY was 301, either because of negative autoimmune markers, diabetes in family history, or slight hyperglycemia, with no need for insulin treatment. Patient’s age was not considered a selection criterion for genetic counseling. Targeted gene (GCK, HNF1A, HNF4A) panel was used during 2017-2022. The values presented as median (min;max), unless stated otherwise.

Results: The median age of patients was 23. 5 (7;74) years; the median duration of diabetes was 6. 0 (2;55) years at the analysis. The median age at diabetes diagnosis was 18. 3 (4;68) years. Twenty-nine (56, 9%) patients had confirmed MODY diagnosis up to the age of 25 years. Twenty-five (86, 2%) of them were diagnosed with GCK, 3 (10, 3%) – HNF1A, 1 (3, 4%) – HNF4A mutations. 65, 5% (n = 19) had positive family history for diabetes, either MD or type 1, or type 2 diabetes. Twenty-two (43, 1%) of patients were diagnosed with MODY after the age of 25, with GCK most frequently - 17 patients (77, 3%), followed by HNF1A – 4 (18, 2%), and HNF4A – 1 (4, 5%). Eighteen (81, 8%) patients had positive family history for diabetes.

Conclusions: This study demonstrated a high diagnostic yield (17. 9%) for MODY among patients referred for genetic testing, with GCK mutations identified as the most prevalent etiology. Furthermore, the findings underscore the necessity of critically evaluating selection criteria for MD genetic testing, as over 40% of diagnosed cases were older than 25 years, including individuals in their late 40s and 50s. These results suggest that expanding genetic screening criteria may facilitate the identification of previously undiagnosed cases of MD, contributing to improved clinical management and risk stratification.