MODY3 and Pancreatic Transplant: Making a Case for Universal MODY Screening Before Transplant

ABSTRACT Objective: Maturity onset diabetes of the young (MODY) comprise a group of autosomal dominant forms of diabetes and account for approximately 1 to 2% of diabetes. Of these, MODY3 is the most common form, and patients are often misdiagnosed as having type 1 diabetes mellitus (T1D). Moreover, many of these patients develop end-stage renal disease. Because of this, there is frequent clinical discussion as to whether simultaneous pancreas and kidney transplantation is warranted. Although MODY3 can often be treated with sulfonylureas, many of these patients have never received this class of drugs. This raises an important clinical question: should sulfonylureanaïve MODY3 patients undergo pancreas transplants? Methods: We present the case of a 31-year-old female with a history of T1D and end-stage renal disease. Results: After receiving a living-donor kidney transplant, the patient's C-peptide level was detectable during evaluation for a pancreas transplant. Genetic testing was performed due to an extensive family history of T1D. She was positive for a mutation in the hepatocyte nuclear factor-1α (HNF1A) gene (R272H), which was consistent with MODY3. Initiation of sulfonylurea treatment allowed her to transition off insulin and be managed with only a sulfonylurea. Thanks to her diagnosis, 2 family members were subsequently diagnosed with MODY3 and transitioned off insulin. Conclusions: This clinical scenario prompted us to suggest that sulfonylurea-naïve MODY3 patients should be treated with sulfonylureas prior to consideration for a pancreas transplant. Moreover, it may also be warranted to screen for MODY in patients with presumed T1D who are being considered for pancreas transplant. Abbreviations: HNF1A hepatocyte nuclear factor-1α MODY maturity onset diabetes of the young T1D type 1 diabetes mellitus