ESPE Abstracts

Introduction: Monogenic diabetes accounts for approximately 3.5% of patients manifesting diabetes till 30 years. Majority of these patients had subtypes of Maturity-Onset Diabetes of the Young (MODY) caused by disruption of the genes encoding glucokinase (GCK), hepatocyte nuclear factor 1-alpha (HNF1A) or 4-alpha (HNF4A), respectively. However, also rare forms of monogenic diabetes could be detected particularly thanks to massive parallel sequencing techniques. We aimed to describe rare forms of monogenic (non)syndromic diabetes in a Czech registry of patients susceptible for monogenic diabetes.

Methods: Probands with pathogenic variants in all pancreas-related but major MODY genes were selected. Data were obtained from the clinical questionnaires. The genetic testing was performed by Sanger sequencing, MLPA, followed by targeted Next Generation Sequencing panel of 52 (63) genes since 2018.

Results: Out of 1903 probands with suspected monogenic diabetes, rare forms were detected in 51 families (84 persons). Median age at diabetes diagnosis was 17 (13-30) years. Median HbA1c reached 57 (45-70) mmol/mol (7.4%; 6.3-8.6%). Insulin was prevailing type of treatment (53/84, 63%), followed by diet (18/84, 21%) and oral antidiabetic drugs (13/84, 15%).

Interpretation: Rare forms of monogenic diabetes caused by variants in 10 genes accounted for 6.9% of all families with genetically confirmed monogenic diabetes. Genetic diagnosis not only clarify the diabetes aetiology but importantly allow to specifically investigate and treat in time additional comorbidities in probands with syndromic monogenic diabetes mimicking as “diabetes only” phenotype.