A Nonsense GATA6 Mutation Explains History of Congenital Heart Defects and 10 Years of Poorly-Controlled Diabetes Lacking DKA in a Non-Obese 30 Year-Old Incidentally Found to Have Pancreatic Hypoplasia

ABSTRACT Objective To report a case of diabetes mellitus (DM) associated with partial pancreatic agenesis and congenital heart disease (CHD) in a patient found to have a nonsense mutation of the GATA6 gene. Methods We present the imaging, laboratory, and genetic findings, and describe the clinical course of a patient with an atypical presentation of DM as well as CHD, who was found to have partial pancreatic agenesis on computed tomography (CT) imaging. Genetic testing was performed to identify monogenic DM. Results A 30-year-old nonobese female with a waxing and waning pattern of insulin-dependent DM diagnosed at the age of 20 was found to have partial pancreatic agenesis on CT scan. It was unclear whether the patient was experiencing undetected hyperglycemia prior to initial diagnosis of DM. She had no history of diabetic ketoacidosis (DKA) despite poorly-controlled diabetes and years without insulin treatment. The patient also had congenital tricuspid atresia, ventricular septal defect, and transposition of the great vessels with surgical correction in childhood. Partial pancreatic agenesis and CHD with atypical DM prompted genetic testing for monogenic DM, and a nonsense mutation of the GATA6 (c.1242C>A, p.C414*) gene was found. Conclusion GATA6 mutations are associated with a broad spectrum of diabetic phenotypes, pancreatic agenesis, and a variety of CHDs. This case highlights the importance of considering monogenic diabetes in young, nonobese patients with diabetes, particularly with negative pancreatic antibodies and no history of DKA. Further, this case demonstrates the importance of testing for GATA6 mutations in any young patient with diabetes and CHD.