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

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Männistö , J M E , Maria , M , Raivo , J , Kuulasmaa , T , Otonkoski , T , Huopio , H & Laakso , M 2020 , ' Clinical and Genetic Characterization of 153 Patients with Persistent or Transient Congenital Hyperinsulinism ' , Journal of Clinical Endocrinology and Metabolism , vol. 105 , no. 4 , 271 . https://doi.org/10.1210/clinem/dgz271

Title: Clinical and Genetic Characterization of 153 Patients with Persistent or Transient Congenital Hyperinsulinism
Author: Männistö, Jonna M. E.; Maria, Maleeha; Raivo, Joose; Kuulasmaa, Teemu; Otonkoski, Timo; Huopio, Hanna; Laakso, Markku
Other contributor: University of Helsinki, Helsinki One Health (HOH)






Date: 2020-04
Language: eng
Number of pages: 9
Belongs to series: Journal of Clinical Endocrinology and Metabolism
ISSN: 0021-972X
DOI: https://doi.org/10.1210/clinem/dgz271
URI: http://hdl.handle.net/10138/327963
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. K-ATP 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.
Subject: hyperinsulinemic hypoglycemia
genetics
genotype-phenotype correlation
INSULIN-RESPONSE TESTS
GLUTAMATE-DEHYDROGENASE
HYPOGLYCEMIA
MUTATIONS
ABCC8
MANAGEMENT
DIAGNOSIS
INFANTS
HYPERAMMONEMIA
CHILDREN
3121 General medicine, internal medicine and other clinical medicine
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