Co-inheritance of Rare Variants of Maturity-Onset Diabetes of the Young (MODY): A Case Report and Review of the Literature

Maturity onset diabetes of the young (MODY) is a rare, monogenic autosomal dominant form of diabetes that is characterized by early-onset, non-insulin-dependent hyperglycemia, strong family history, and is often misdiagnosed as type 1 or type 2 diabetes. Co-inheritance of multiple MODY genes, however, is rare. We describe here a case of MODY involving co-inherited rare variants in the ABCC8 and B-lymphocyte kinase (BLK) genes. A 55-year-old non-obese man with a past medical history of dyslipidemia and premature ischemic heart disease was initially misdiagnosed with type 2 diabetes for more than 18 years. He is a smoker with a strong family history of diabetes affecting both of his parents and most of his siblings. Despite treatment with different oral antihyperglycemics, his diabetes remained uncontrolled with glycated hemoglobin (HBA1c) between 8 and 10% until the addition of gliclazide, which improved his HBA1c to 5.7%. Based on all the previous information, MODY was suspected, and genetic testing was done, which showed rare variants in the BLK and ABCC8 genes and suggested a co-occurrence of MODY11 and MODY12. This case highlights the importance of accurate genetic testing, which is crucial for proper MODY subtyping, enabling tailored treatment strategies and potentially improving patient outcomes. Moreover, the consistent presence of the BLK gene variant in limited cases of co-inheritance raises questions about its causative role in MODY, suggesting a need for further investigation into its clinical significance.