Clinical and Laboratory ObservationHepatocyte Nuclear Factor 4α Gene Mutation Associated with Familial Neonatal Hyperinsulinism and Maturity-Onset Diabetes of the Young
Section snippets
Case History
A 17-year-old normal-weight (body mass index, 25.0 kg/m2) Caucasian female with hyperglycemia had a history of birth at 37 weeks gestation with a birth weight of 4454 g (>97th percentile). At 3 days of life, she had symptomatic hypoglycemia (0.33 mmol/L) with elevated plasma insulin (41 μU/mL), leading to a diagnosis of neonatal hyperinsulinism. Treatment with diazoxide was considered, but the parents opted for frequent feeds. Glycemia and frequency of feeding were normal by 3 years of age.
MODY
Discussion
Mutations in HNF4A are a direct cause of MODY, a form of impaired insulin secretion with autosomal dominant inheritance.1 Decreased functional HNF4α impairs β cell function,10 manifesting as alterations in the dose‒response relationship between plasma glucose concentration and insulin secretion rate.11 However, HNF4α proteins exist as part of a transcription control network.12 HNF4α regulates expression of HNF1A, mutations in which are associated with HNF1α-MODY, the most common cause of
References (15)
- et al.
Standardization of the oral glucose tolerance test and the criteria for diagnosis of chemical diabetes in children
Metabolism
(1973) - et al.
The maturity-onset diabetes of the young (MODY1) transcription factor HNF4α regulates expression of genes required for glucose transport and metabolism
Proc Natl Acad Sci USA
(1997) - et al.
Species-specific differences in the expression of the HNF1A, HNF1B and HNF4A genes
PLoS One
(2009) - et al.
Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young
N Engl J Med
(2001) - et al.
Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene
PLoS Med
(2007) - et al.
Persistent hyperinsulinemic hypoglycemia and maturity-onset diabetes of the young due to heterozygous HNF4A mutations
Diabetes
(2008) - et al.
Diazoxide-responsive hyperinsulinemic hypoglycemia caused by HNF4A gene mutations
Eur J Endocrinol
(2010)
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The authors declare no conflicts of interest.