SummaryNeonatal hypoglycemia is a serious condition that can have a major impact on the growing neonatal brain. The differential diagnosis of neonatal hypoglycemia is broad and includes hyperinsulinism as well as panhypopituitarism. TheFOXA2gene has been involved in the development of the pancreas as well as the pituitary gland. Six cases have been reported thus far withFOXA2mutations presenting with variable degrees of hypopituitarism, and only two patients had permanent hyperinsulinism; other cases have been reported with microdeletions in 20p11, the location that encompassesFOXA2, and those patients presented with a wider phenotype. A full-term female infant presented with severe hypoglycemia. Critical sampling showed an insulin of 1 mIU/mL, suppressed beta-hydroxybutyric acids, and suppressed free fatty acids. Blood glucose responded to glucagon administration. Growth hormone (GH) stimulation test later showed undetectable GH in all samples, and cortisol failed to respond appropriately to stimulation. Gonadotropins were undetectable at 1 month of life, and MRI showed ectopic posterior pituitary, interrupted stalk, hypoplastic anterior pituitary, cavum septum pellucidum, and diminutive appearance of optic nerves. Whole-exome sequencing revealed a likely pathogenicde novo c.604 T>C, p.Tyr202His FOXA2mutation. We expand the known phenotype onFOXA2mutations and report a likely pathogenic, novel mutation associated with hyperinsulinism and panhypopituitarism.Learning pointsFOXA2has been shown to play an important role in the neuroectodermal and endodermal development.FOXA2mutation may lead to the rare combination of hyperinsulinism and panhypopituitarism.Patients reported so far all responded well to diazoxide. Dysmorphology may be subtle, and liver functions should be monitored.