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Diazoxide-responsive hyperinsulinemic hypoglycemia caused by HNF4A gene mutations
S E Flanagan1, R R Kapoor, G Mali
1Peninsula Medical School, Institute of Biomedical and Clinical Science, University of Exeter, Exeter, UK.
European Journal of Endocrinology
|February 19, 2010
Summary
HNF4A gene mutations are a common cause of diazoxide-responsive hyperinsulinemic hypoglycemia (HH) in newborns. Genetic testing for HNF4A is recommended for infants with HH, even without a family history of diabetes.
Area of Science:
- Genetics
- Endocrinology
- Neonatal Medicine
Background:
- Heterozygous HNF4A mutations are linked to diazoxide-responsive neonatal hypoglycemia and MODY.
- Previous HNF4A mutation screening focused on patients with a family history of MODY.
Purpose of the Study:
- To determine the prevalence of HNF4A mutations in a large cohort of patients with diazoxide-responsive hyperinsulinemic hypoglycemia (HH).
Main Methods:
- Sequencing of ABCC8, KCNJ11, GCK, GLUD1, and HNF4A genes in 220 patients with diazoxide-responsive HH.
- Genetic testing order was based on clinical phenotype.
Main Results:
- Genetic diagnosis was achieved in 27% of patients.
- HNF4A mutations were identified in 5% of patients.
- Seven of 11 patients with HNF4A mutations lacked a family history of diabetes; four de novo mutations were confirmed.
Conclusions:
- HNF4A mutations are the third most frequent cause of diazoxide-responsive HH.
- HNF4A sequencing should be considered for all neonates with diazoxide-responsive HH diagnosed within the first week of life, regardless of family history, after excluding K(ATP) channel mutations.
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