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Clinical and Genetic Characterization of 153 Patients with Persistent or Transient Congenital Hyperinsulinism
- Source :
- The Journal of Clinical Endocrinology & Metabolism. 105:e1686-e1694
- Publication Year :
- 2020
- Publisher :
- The Endocrine Society, 2020.
-
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.
- Subjects :
- Male
Pathology
Endocrinology, Diabetes and Metabolism
Clinical Biochemistry
INFANTS
CHILDREN
Disease
Sulfonylurea Receptors
medicine.disease_cause
Biochemistry
Germinal Center Kinases
0302 clinical medicine
Endocrinology
Glutamate Dehydrogenase
genetics
Child
Finland
0303 health sciences
GLUTAMATE-DEHYDROGENASE
Symporters
medicine.diagnostic_test
biology
Prognosis
3. Good health
Hepatocyte Nuclear Factor 4
Child, Preschool
Cohort
Female
Monocarboxylic Acid Transporters
medicine.medical_specialty
030209 endocrinology & metabolism
Context (language use)
genotype-phenotype correlation
Hypoglycemia
DIAGNOSIS
ABCC8
HYPOGLYCEMIA
03 medical and health sciences
030225 pediatrics
Internal medicine
MANAGEMENT
medicine
Humans
Transient (computer programming)
Potassium Channels, Inwardly Rectifying
Hyperinsulinemic hypoglycemia
Genetic Association Studies
Retrospective Studies
030304 developmental biology
Genetic testing
MUTATIONS
business.industry
Biochemistry (medical)
Infant, Newborn
Infant
medicine.disease
Cross-Sectional Studies
INSULIN-RESPONSE TESTS
3121 General medicine, internal medicine and other clinical medicine
Mutation
biology.protein
Congenital hyperinsulinism
hyperinsulinemic hypoglycemia
Congenital Hyperinsulinism
business
HYPERAMMONEMIA
Biomarkers
Follow-Up Studies
Subjects
Details
- ISSN :
- 19457197 and 0021972X
- Volume :
- 105
- Database :
- OpenAIRE
- Journal :
- The Journal of Clinical Endocrinology & Metabolism
- Accession number :
- edsair.doi.dedup.....def39c6919ce2c40c2abb17f72f5114b