Pathogenic HNF1A Variant in an Indonesian Family: Atypical Management of MODY3 Guided by Patient Comorbidity

Maturity-onset diabetes of the young (MODY) is an autosomal dominant form of monogenic diabetes frequently misdiagnosed as type 1 or type 2 diabetes. Identifying the specific subtype is crucial, as several subtypes, such as HNF1A-MODY (MODY-3), are typically well-controlled with sulfonylureas.

A 19-year-old male with a history of diabetes presented with right-sided weakness, aphasia, and facial asymmetry. He was admitted for gamma knife radiosurgery to treat a left basal ganglia arteriovenous malformation. One month prior to this admission, he had undergone surgical evacuation of an intracranial hemorrhage-a complication of his arteriovenous malformation-at another hospital. He was discharged on a basal-bolus insulin regimen due to hyperglycemia during that hospitalization and was subsequently referred to our center. During the current admission, glycemic control was achieved, allowing gradual reduction of insulin dose and transition to oral sitagliptin/metformin XR upon discharge. Genetic testing later confirmed a pathogenic c.160C>T variant in the HNF1A gene, which was also identified in his mother and younger sibling. At the 2-month follow-up, due to sustained glycemic control, his treatment was simplified to sitagliptin 100 mg monotherapy.

Although sulfonylureas are typically the first-line treatment for HNF1A-MODY, individualized therapy was required due to the patient's neurological comorbidities. dipeptidyl peptidase-4 inhibitor therapy provided effective glycemic control and offered potential neurocognitive benefits.

This case underscores that while genetic confirmation of HNF1A-MODY guides therapy, treatment should be individualized based on comorbidities and prior medication history to optimize glycemic control.