| Persistent hyperinsulinemic hypoglycemia and maturity-onset diabetes of the young due to heterozygous HNF4A mutations. | |
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MedLine Citation:
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PMID: 18268044 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: Mutations in the human HNF4A gene encoding the hepatocyte nuclear factor (HNF)-4alpha are known to cause maturity-onset diabetes of the young (MODY), which is characterized by autosomal-dominant inheritance and impaired glucose-stimulated insulin secretion from pancreatic beta-cells. HNF-4alpha has a key role in regulating the multiple transcriptional factor networks in the islet. Recently, heterozygous mutations in the HNF4A gene were reported to cause transient hyperinsulinemic hypoglycemia associated with macrosomia. RESEARCH DESIGN AND METHODS: Three infants presented with macrosomia and severe hypoglycemia with a positive family history of MODY. The hypoglycemia was confirmed to be due to hyperinsulinism, and all three patients required diazoxide therapy to maintain normoglycemia. Two of the three infants are still requiring diazoxide therapy at 8 and 18 months, whereas one of them had resolution of hyperinsulinemic hypoglycemia at 32 months of age. RESULTS: Sequencing of the HNF4A gene identified heterozygous mutations in all three families. In family 1, a frameshift mutation L330fsdel17ins9 (c.987 1003del17ins9; p.Leu330fs) was present in the proband; a mutation affecting the conserved A nucleotide of the intron 2 branch site (c.264-21A>G) was identified in the proband of family 2; and finally a nonsense mutation, Y16X (c.48C>G, p.Tyr16X), was found in the proband of family 3. CONCLUSIONS: Heterozygous HNF4A mutations can therefore cause both transient and persistent hyperinsulinemic hypoglycemia associated with macrosomia. We recommend that macrosomic infants with transient or persistent hyperinsulinemic hypoglycemia should be screened for HNF4A mutations if there is a family history of youth-onset diabetes. |
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Authors:
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Ritika R Kapoor; Jonathan Locke; Kevin Colclough; Jerry Wales; Jennifer J Conn; Andrew T Hattersley; Sian Ellard; Khalid Hussain |
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Publication Detail:
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Type: Case Reports; Journal Article; Research Support, Non-U.S. Gov't Date: 2008-02-11 |
Journal Detail:
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Title: Diabetes Volume: 57 ISSN: 1939-327X ISO Abbreviation: Diabetes Publication Date: 2008 Jun |
Date Detail:
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Created Date: 2008-05-30 Completed Date: 2008-08-01 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372763 Medline TA: Diabetes Country: United States |
Other Details:
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Languages: eng Pagination: 1659-63 Citation Subset: AIM; IM |
Affiliation:
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London Centre for Paediatric Endocrinology and Metabolism, Great Ormond Street Hospital for Children NHS Trust, and The Institute of Child Health, University College London, London, UK. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Age of Onset Birth Weight DNA Transposable Elements Diabetes Mellitus, Type 2 / genetics* Female Fetal Macrosomia / genetics Frameshift Mutation Hepatocyte Nuclear Factor 4 / genetics* Heterozygote Detection Humans Hyperinsulinism / genetics* Hypoglycemia / genetics* Infant Infant, Newborn Male Mutation* Pedigree Sequence Deletion |
| Grant Support | |
ID/Acronym/Agency:
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081188/A/06/Z//Wellcome Trust |
| Chemical | |
Reg. No./Substance:
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0/DNA Transposable Elements; 0/HNF4A protein, human; 0/Hepatocyte Nuclear Factor 4 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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