A Case of Maturity-Onset Diabetes of the Young With Complex Mutations

TL;DR

A 33-year-old man with a complex genetic case of maturity-onset diabetes of the young (MODY) is described, highlighting the importance of genetic testing for accurate diagnosis and treatment.

Contribution

The paper presents a rare MODY case involving mutations in two genes, emphasizing the need for genetic testing in similar clinical scenarios.

Findings

The patient had pathogenic variants in HNF4A and a variant of unknown significance in PAX4.

Switching treatment to glipizide improved glycemic control.

Genetic testing is recommended for family members due to inherited risk.

Abstract

Maturity-onset diabetes of the young (MODY) encompasses a group of rare monogenic forms of diabetes, with 14 subtypes described in the literature, each with a distinct underlying genetic mutation. We present a case with mutations in 2 different genes that are known to be responsible for MODY. A 33-year-old male individual presented to the endocrinology clinic for evaluation. He was diagnosed with type 2 diabetes mellitus at 13 years of age and was initially treated with insulin, which was subsequently switched to repaglinide and metformin. The patient reported a history of hypoglycemia at birth and in his daughter. His biological father was diagnosed with diabetes mellitus at 16 years of age. Genetic testing for monogenic diabetes revealed a pathogenic variant in hepatocyte nuclear factor 4 alpha and a variant of unknown significance in Paired Box Gene 4. The treatment was switched to glipizide 2.5 mg orally, which resulted in adequate glycemic control. Genetic testing was recommended for his daughter. MODY can be missed because of its broad clinical presentation. Heightened vigilance and a low threshold for genetic testing for MODY are required in patients with a high likelihood of having MODY, as the treatment can be tailored to individual patient needs.