Novel Hypoglycemia Phenotype in Congenital Hyperinsulinism Due to Dominant Mutations of Uncoupling Protein 2 (UCP2).

Context:The rarest genetic form of congenital hyperinsulinism (HI) has been associated with dominant inactivating mutations in uncoupling protein 2 (UCP2), a mitochondrial inner membrane carrier that modulates the oxidation of glucose vs amino acids.Objective:To evaluate the frequency of UCP2 mutations in children with HI and phenotypic features of this form of HI.Design:We examined 211 children with diazoxide-responsive HI seen at The Children’s Hospital of Philadelphia (CHOP) between 1997 and October 2016.Setting:CHOP Clinical and Translational Research Center.Results:We identified five unrelated children with UCP2 mutations out of 211 cases of diazoxide-responsive HI (5/211, 2.4%). These five children were diagnosed with HI before six months of age; diazoxide treatment was only partly effective in three of the five. Among the five cases, four unique mutations were identified: three missense and one splicing mutation. Three mutations were novel and one was previously reported. In-vitro functional assays...