Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene
2007

HNF4A Mutations and Their Impact on Birthweight and Neonatal Hypoglycaemia

Sample size: 242 publication Evidence: high

Author Information

Author(s): Ewan R. Pearson, Sylvia F. Boj, Anna M. Steele, Timothy Barrett, Karen Stals, Julian P. Shield, Sian Ellard, Jorge Ferrer, Andew T. Hattersley

Primary Institution: Peninsula Medical School, Exeter, United Kingdom

Hypothesis

Mutations in the HNF4A gene increase foetal insulin secretion, leading to higher birthweight and neonatal hypoglycaemia.

Conclusion

HNF4A mutations are associated with a considerable increase in birthweight and macrosomia, and are a novel cause of neonatal hypoglycaemia.

Supporting Evidence

  • HNF4A-mutation carriers had a median birthweight increase of 790 g compared to non-mutation carriers.
  • 56% of HNF4A-mutation carriers were macrosomic compared to 13% of non-mutation carriers.
  • Transient hypoglycaemia was reported in 8 out of 54 infants with HNF4A mutations.

Takeaway

Babies with certain gene mutations can be much heavier than normal and may have low blood sugar right after birth.

Methodology

The study examined birthweight and hypoglycaemia in patients with HNF4A and HNF1A mutations, comparing them to unaffected family members.

Potential Biases

The retrospective nature of the study may lead to underreporting of hypoglycaemia cases.

Limitations

Data on birthweight and gestational age were primarily obtained by maternal recall, which may introduce bias.

Participant Demographics

108 patients with HNF4A mutations and 134 patients with HNF1A mutations from multiple families.

Statistical Information

P-Value

p<0.001

Statistical Significance

p<0.001

Digital Object Identifier (DOI)

10.1371/journal.pmed.0040118

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