Diabetes mellitus diagnosed in young adulthood is often classified as type 1 (T1DM) or early-onset type 2 diabetes (T2DM); however, atypical features should prompt consideration of maturity-onset diabetes of the young (MODY) and other forms of monogenic diabetes [1,2]. We present a case series illustrating the diagnostic challenges and clinical impact of recognising monogenic diabetes.

We retrospectively reviewed patients with genetically confirmed monogenic diabetes who were referred to the multidisciplinary Young Adult and Atypical Diabetes Service at Royal Prince Alfred Hospital. Clinical features, diagnostic investigations, and treatment outcomes were described.

Five patients (four female, one male) with genetically confirmed monogenic diabetes were identified, representing diverse phenotypes including GCK-, HNF1A-, HNF4A-, HNF1B-, and mitochondrial diabetes (Table 1). Among the four patients initially classified as T2DM, the median delay to genetic diagnosis was 12 years (range 5–22 years). Common features prompting genetic testing included young age at diabetes diagnosis (median 27 years), preserved C-peptide, negative pancreatic autoantibodies, absence of features of metabolic syndrome, a multigenerational family history consistent with autosomal dominant inheritance, and extra-pancreatic manifestations suggestive of monogenic diabetes. Genetic diagnoses informed genotype-specific management, including withdrawal of unnecessary glucose-lowering therapy, selection of sulfonylurea versus insulin therapy, targeted surveillance for multiorgan complications, and cascade testing of relatives, facilitating earlier diagnosis within affected families.

Monogenic diabetes remains under-recognised in young adults and is frequently misclassified as T1DM or T2DM. A high index of suspicion, guided by clinical phenotype, is essential to facilitate timely genetic testing. Genetic diagnosis carries important therapeutic, prognostic and familial implications that extend beyond glycaemic management alone.