Format

Send to

Choose Destination
J Clin Endocrinol Metab. 2020 Apr 1;105(4). pii: dgz271. doi: 10.1210/clinem/dgz271.

Clinical and Genetic Characterization of 153 Patients with Persistent or Transient Congenital Hyperinsulinism.

Author information

1
Department of Pediatrics, University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland.
2
Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland.
3
Institute of Clinical Medicine, Internal Medicine, and Institute of Biomedicine, Bioinformatics Center, University of Eastern Finland, Kuopio, Finland.
4
Children's Hospital, University of Helsinki, and Helsinki University Hospital, Helsinki, Finland.
5
Department of Pediatrics, Kuopio University Hospital, Kuopio, Finland.
6
Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, and Kuopio University Hospital Kuopio, Finland.

Abstract

CONTEXT:

Major advances have been made in the genetics and classification of congenital hyperinsulinism (CHI).

OBJECTIVE:

To examine the genetics and clinical characteristics of 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 153 patients with persistent (n = 95) and transient (n = 58) CHI diagnosed between 1972 and 2015. Of these, 86 patients with persistent and 58 with transient CHI participated in the analysis of the selected 104 genes affecting glucose metabolism, including 10 CHI-associated genes, and 9 patients with persistent CHI were included because of their previously confirmed genetic diagnosis.

MAIN OUTCOME MEASURES:

Targeted next-generation sequencing results and genotype-phenotype associations.

RESULTS:

Five novel and 21 previously reported pathogenic or likely pathogenic variants in ABCC8, KCNJ11, GLUD1, GCK, HNF4A, and SLC16A1 genes were found in 68% (n = 65) and 0% of the patients with persistent and transient CHI, respectively. KATP channel mutations explained 82% of the mutation positive cases.

CONCLUSIONS:

The genetic variants found in this nationwide CHI cohort are in agreement with previous studies, mutations in the KATP channel genes being the major causes of the disease. Pathogenic CHI-associated variants were not identified in patients who were both diazoxide responsive and able to discontinue medication within the first 4 months. Therefore, our results support the notion that genetic testing should be focused on patients with inadequate response or prolonged need for medication.

KEYWORDS:

genetics; genotype–phenotype correlation; hyperinsulinemic hypoglycemia

PMID:
32170320
DOI:
10.1210/clinem/dgz271

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center