From Misdiagnosis to Precision: Genetic Testing Reveals MODY in Adolescents Initially Treated as Type 1 Diabetes

Maturity-Onset Diabetes of the Young (MODY) is a heterogeneous form of clinical monogenic diabetes caused by genetic abnormalities resulting in an autosomal dominant mode of inheritance. MODY accounts for approximately 4.8-10.9% of diabetes cases worldwide; its clinical characteristics often resemble those of Type 1 Diabetes Mellitus (T1DM) and Type 2 Diabetes Mellitus (T2DM), causing underdiagnosis. In this study, we have presented three cases, initially diagnosed with T1DM but later identified as Monogenic Diabetes (MODY) caused by mutations in the HNF1A and HNF4A genes. All patients, despite insulin therapy, suffered from recurrent Diabetic Ketoacidosis (DKA) and poor glycaemic control, prompting further investigation. Genetic analysis revealed two instances of HNF1A (MODY3) mutations and one case of HNF4A (MODY1) mutation. These findings were pivotal in reclassifying the patients' conditions from T1DM to MODY. Understanding the genetic mutations, the patients were switched to a minimal sulfonylurea regimen, resulting in significant improvement in blood glucose control and a reduction in DKA episodes. The studies emphasise the significance of genetic testing in accurately diagnosing MODY and tailoring a personalised treatment with oral sulfonylureas.