HNF1B-MODY (MODY-5): a rare form of diabetes with multisystemic features-two case reports

Maturity-Onset Diabetes of the Young (MODY) is a rare monogenic form of diabetes characterized by early onset and autosomal dominant inheritance. MODY-5, caused by HNF1B gene mutations, accounts for <5% of MODY cases and often presents with renal abnormalities and genitourinary malformations.

We describe two patients with HNF1B-related MODY confirmed by heterozygous 17q12 microdeletions. The first case, a 29-year-old woman, presented with diabetes, hypertension, bilateral renal cysts, mild chronic kidney disease (CKD), hypomagnesemia, mild liver enzyme elevations, and a complex Müllerian anomaly requiring surgical correction. She has maintained excellent metabolic control on metformin alone, with no diabetic complications after four years of follow-up. The second case, a 40-year-old man, had a history of diabetes, neonatal left nephrectomy for cystic dysplasia, CKD stage G3bA2, persistent liver enzyme elevation, dorsal pancreatic agenesis, hypomagnesemia, hyperuricemia, mild cognitive impairment, and infertility. He initially achieved good glycemic control with a combination of insulin, metformin, liraglutide, and dapagliflozin, though control subsequently fluctuated. To date, microalbuminuria remains his only diabetes-related complication.

These cases underscore the broad phenotypic spectrum of MODY 5 and highlight the importance of considering HNF1B mutations in young-onset diabetes associated with renal or genitourinary anomalies. Hypomagnesemia and abnormal liver function tests are additional features that may guide suspicion. Early recognition and genetic confirmation are essential for tailored management, complication surveillance, and family screening.