LAUSR

AIMS Monogenic diabetes (also known as maturity-onset diabetes of the young or MODY) affects a subset of individuals with young-onset diabetes. We report our diagnostic work-up experience for such individuals. METHODS Serving as a regional secondary-care diabetes centre in a multi-ethnic population, we receive referrals to evaluate MODY from endocrinologists in both public and private practice. Key criteria for consideration of genetic-testing are onset age ≤35, negative GAD antibody, no history of diabetic ketoacidosis, strong family history of diabetes and BMI<32.5 kg/m2. A monogenic diabetes registry was set up since 2017 to study their disease trajectories. RESULTS We identified 30 out of 175 (17.1%) individuals with likely pathogenic/pathogenic variants. Importantly, 29 out of 30 (96.7%) occurred in clinically actionable genes. A continuous scale combining BMI, hs-CRP and HDL provided 80% (P<0.001) diagnostic accuracy for MODY in our cohort, achieving a negative predictive value of 0.93 and sensitivity at 0.76. Subtyping MODY prior to genetic testing (if desired) will require specialist domain knowledge and additional biomarkers due to its genetic heterogeneity. CONCLUSIONS Through systematic and structured evaluation, the prevalence of MODY is non-trivial (17.1%) in a referral centre. Diagnostic algorithm combining clinical criteria and readily available biomarkers can support clinical decision for MODY genetic testing.