Antenatal management of HNF4A-MODY and INSR mutations in pregnancy

We report the case of a pregnant woman with coexisting pathogenic hepatocyte nuclear factor 4 alpha (HNF4A) and insulin receptor (INSR) gene variants. A 25-year-old lean Caucasian gravida 1, para 0 (G1P0) woman with a history of early-onset diabetes and features of insulin resistance, was referred at 6 weeks' gestation. Molecular testing confirmed pathogenic variants in HNF4A and INSR. Noninvasive prenatal testing predicted fetal inheritance of the HNF4A variant. Despite good maternal glycemic control and relatively low insulin requirements, the infant was macrosomic and developed persistent postnatal hypoglycemia requiring prolonged diazoxide therapy. This case highlights the importance of early recognition of monogenic diabetes in pregnancy, the potential utility of noninvasive prenatal testing, and the observation of persistent hyperinsulinemia beyond the neonatal period in HNF4A-related diabetes.