Context: Major advances have been made in the genetics and classification of congenital hyperinsulinism (CHI; OMIM #256450).
Objective: To examine the molecular and clinical characteristics of the Finnish patients with persistent and transient CHI.
Design: A cross-sectional study with the register data and targeted sequencing of 104 genes affecting glucose metabolism.
Patients: Genetic and phenotypic data were collected from 148 patients with persistent (n=92) and transient (n=56) CHI diagnosed between 1972 and 2015. A total of 88 patients with persistent and 56 with transient CHI were included in the analysis of 104 genes affecting glucose metabolism, including ten CHI-associated genes.
Main outcome measures: Targeted next-generation sequencing results and genotype-phenotype associations.
Results: Sixnovel and 20 previously reported pathogenic or likely pathogenic variants in ABCC8, KCNJ11, GLUD1, GCK, HNF4A and SLC16A1 genes were found in 70% (n=64) and 0% of the patients with persistent and transient CHI, respectively. KATP channel variants explained 58% of the mutation positive cases.
Conclusions: KATPchannel gene mutations explained a majority of the genetic etiology of CHI in our study. Genotype-phenotype associations showed wide phenotypic diversity. Therefore, next generation sequencing should be applied in the diagnostics of CHI.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology