Work

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

Year: 2025

Type: article

Abstract: Background/Objective 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. Case Description 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 (AVM). One month prior to this admission, he had undergone surgical evacuation of an intracranial hemorrhage— a complication of his AVM—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 two-month follow-up, due to sustained glycemic control, his treatment was simplified to sitagliptin 100 mg monotherapy. Discussion Although sulfonylureas are typically the first-line treatment for HNF1A -MODY, individualized therapy was required due to the patient's neurological comorbidities. DPP-4 inhibitor therapy provided effective glycemic control and offered potential neurocognitive benefits. Conclusion 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.

Source: AACE Endocrinology and Diabetes

DOI: 10.1016/j.aed.2025.10.006

Authors: Ardy Wildan, Fergie Marie Joe Grizella Runtu, Mentari Kasih, Selvi Nafisa Shahab, Dicky Levenus Tahapary

Institutions: University of Indonesia, Rumah Sakit Umum Pusat Nasional Dr. Cipto Mangunkusumo

Language: English

Topic: Diabetes and associated disorders

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Funder: Ministry of Health of the Republic of Indonesia