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Clinical heterogeneity of hyperinsulinism due to HNF1A and HNF4A mutations
Author(s) -
Tung Joanna Yuetling,
Boodhansingh Kara,
Stanley Charles A,
De León Diva D
Publication year - 2018
Publication title -
pediatric diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.678
H-Index - 75
eISSN - 1399-5448
pISSN - 1399-543X
DOI - 10.1111/pedi.12655
Subject(s) - congenital hyperinsulinism , medicine , hnf1a , proband , hyperinsulinemic hypoglycemia , hyperinsulinism , pediatrics , hypoglycemia , diabetes mellitus , endocrinology , mutation , genetics , gene , insulin resistance , biology
Background Dominant inactivating mutations in HNF1A and HNF4A have been described to cause hyperinsulinism (HI) before evolving to diabetes. However, information available in the literature regarding the clinical phenotype is limited. Objective To report the prevalence of HNF1A and HNF4A mutations in a large cohort of children with HI, and to describe their genotypes and phenotypes. Design Retrospective descriptive study. Methods Medical records were reviewed to extract clinical information. Mutation analysis was carried out for 8 genes associated with HI ( ABCC8, KCNJ11 , GLUD1 , GCK , HADH , HNF4A , HNF1A , and UCP2 ). Results HNF1A and HNF4A mutations were identified in 5.9% (12 out of 204; HNF1A = 7, HNF4A = 5) of diazoxide‐responsive HI probands. The clinical phenotypes were extremely variable. Two children showed evidence of ketone production during hypoglycemia, a biochemical profile atypical for hyperinsulinism. At the time of analysis, diazoxide was discontinued in 5 children at a median age of 6.8 years. None had developed diabetes mellitus at a median age of 7.0 years. Conclusions Given the heterogeneous clinical phenotypes of HNF1A‐ and HNF4A‐ HI, all children with transient, diazoxide‐responsive HI without clear history of perinatal stress, should be screened for HNF1A and HNF4A mutations as it predicts the clinical course and affects the subsequent management plan.