2 research outputs found
Corrigendum for: Novel hypoglycemia phenotype in congenital hyperinsulinism due to dominant mutations of uncoupling protein 2 (Journal of Clinical Endocrinology and Metabolism (2017) 102:3 (942-949) DOI: 10.1210/jc.2016-3164)
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 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: Of 211 cases of diazoxide-responsive HI, we identified 5 unrelated children with UCP2
mutations (5 of 211; 2.4%). All 5 were diagnosed with HI before 6 months of age; diazoxide
treatment was only partly effective in 3 of the 5. Among the 5 cases, 4 unique mutations (3 missense
and 1 splicing) were identified. Three mutations were novel; 1 was previously reported. In vitro
functional assays showed 30% to 75% decrease in UCP2 activity. Two of the children, when not
taking diazoxide, developed hypoketotic-hypoglycemia after fasting 15 to 20 hours; a similar trend
toward hypoglycemia after fasting 24 hours occurred in 4 adult carriers. In contrast, both children
and 2 of the 4 carriers developed symptomatic hypoglycemia 4 hours following oral glucose.
Unusual oscillating glucose and insulin responses to oral glucose were seen in both cases and
carriers.
Conclusions: These data indicate that dominant UCP2 mutations are a more important cause of HI
than has been recognized and that affected individuals are markedly hypersensitive to glucoseinduced
hypoglycemia. (J Clin Endocrinol Metab 102: 942–949, 2017