FRI637 Missed MODY With Complex Mutation

Abstract

Abstract Disclosure: S. Bulchandani: None. S. Majety: None. P. Kundra: None. Introduction: The prevalence range of Maturity-Onset Diabetes of the Young (MODY) is 1-5% among all patients diagnosed with diabetes. Strong family history of diabetes is suggestive of autosomal dominant inheritance. The symptoms of MODY range from mild asymptomatic hyperglycemia to overt insulinopenia requiring insulin therapy. Clinical Case: 33-year-old male presented to the endocrinology clinic for evaluation. He was diagnosed with type 2 diabetes mellitus at the age of 13 years and was initially treated with insulin which was subsequently transitioned to repaglinide and metformin. Reported history of hypoglycemia at birth in self and recently born daughter. Family History was significant for diabetes mellitus diagnosed in biological father at the age of 16 years. Genetic testing for monogenic diabetes revealed pathogenic variant in hepatocyte nuclear factor 4 alpha (HNF4a) and variant of unknown significance in Paired Box Gene 4 (PAX4). Therapy was switched to glipizide 2.5 mg orally which resulted in adequate glycemic control. Genetic testing was recommended for his daughter. Conclusion: MODY is a rare condition and because of its wide clinical presentation, it is common for it to be missed. There are about 14 subtypes of MODY with different genetic mutations, each affecting the beta cell function in a different way. Our case is unique given that our patient had two genetic mutations. Amongst all forms of MODY, HNF4a with a prevalence of 5% to 10% is the third most common mutation of MODY. PAX4 is a transcription factor that is critical for the formation of beta cells, and is important as a regulator in commitment of progenitor cells to mature islet cells. Mutations in PAX gene associated with monogenic diabetes were first identified in two patients of Thai origin, who did not present with mutations in the other known MODY genes. There should be high vigilance and low threshold for genetic testing for MODY in patients who have high likelihood of possessing a form of MODY, particularly as the treatment can be tailored to the clinical presentation of the patient.