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Monogenic Hyperinsulinemic Hypoglycemia Disorders

Editor(s): Stanley C.A. (Philadelphia, Pa.) 
De León D.D. (Philadelphia, Pa.) 
Cover

The Molecular Genetics and Pathophysiology of Congenital Hyperinsulinism Caused by Short-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency

Molven A.a,b · Helgeland G.a,c · Sandal T.a,b · Njølstad P.R.c,d

Author affiliations

aThe Gade Institute and Departments of bPathology, cClinical Medicine and dPediactrics, Haukeland University Hospital, University of Bergen, Bergen, Norway

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Stanley CA, De León DD (eds): Monogenic Hyperinsulinemic Hypoglycemia Disorders. Front Diabetes. Basel, Karger, 2012, vol 21, pp 137-145

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Article / Publication Details

First-Page Preview
Abstract of Paper

Published online: February 14, 2012
Cover Date: 2012

Number of Print Pages: 9
Number of Figures: 3
Number of Tables: 1

ISBN: 978-3-8055-9943-6 (Print)
eISBN: 978-3-8055-9944-3 (Online)

Abstract

Deficiency of the metabolic enzyme short-chain 3-hydroxyacyl-CoA (SCHAD) is a rare autosomal recessive form of congenital hyperinsulinism of infancy caused by mutations in the HADH gene on chromosome 4q. Most cases reported to date are from ethnicities where consanguineous marriages are relatively frequent. SCHAD-deficient patients have normal or slightly elevated birth weights. Hypoglycemia most often manifests within the first 6 months of life and is diazoxide-sensitive. Although SCHAD participates in the degradation of fatty acids, the patients usually do not present a clinical picture that would suggest a fatty acid oxidation disorder. Metabolic profiling may, however, reveal an increased level of 3-hydroxybutyryl-carnitine in blood and the presence of 3-hydroxyglutaric acid in urine. Recently, it was demonstrated that SCHAD serves to inhibit the activity of glutamate dehydrogenase in the pancreatic beta-cells, a finding that also explains why SCHAD-deficient patients tend to be protein-intolerant.

© 2012 S. Karger AG, Basel


References

  1. Clayton PT Eaton S Aynsley-Green A Edginton M Hussain K Krywawych S Datta V Malingre HE Berger R Van Den Berg IE: Hyperinsulinism in short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency reveals the importance of beta-oxidation in insulin secretion. J Clin Invest 2001; 108: 457-465
  2. Molven A Matre GE Duran M Wanders RJ Rishaug U Njølstad PR Jellum E Søvik O: Familial hyperinsulinemic hypoglycemia caused by a defect in the SCHAD enzyme of mitochondrial fatty acid oxidation. Diabetes 2004; 53: 221-227
  3. Vidnes J Øyasæter S: Glucagon deficiency causing severe neonatal hypoglycemia in a patient with normal insulin secretion. Pediatr Res 1977; 11: 943-949
  4. Molven A Rishaug U Matre GE Njølstad PR Søvik O: Hunting for a hypoglycemia gene: severe neonatal hypoglycemia in a consanguineous family. Am J Med Genet 2002; 113: 40-46
  5. Filling C Keller B Hirschberg D Marschall HU Jornvall H Bennett MJ Oppermann U: Role of short-chain hydroxyacyl CoA dehydrogenases in SCHAD deficiency. Biochem Biophys Res Commun 2008; 368: 6-11
  6. Martins E Cardoso ML Rodrigues E Barbot C Ramos A Bennett MJ Teles EL Vilarinho L: Shortchain 3-hydroxyacyl-CoA dehydrogenase deficiency: the clinical relevance of an early diagnosis and report of four new cases. J Inherit Metab Dis 2011; 34: 835-842
  7. Kapoor RR James C Flanagan SE Ellard S Eaton S Hussain K: 3-Hydroxyacyl-coenzyme A dehydrogenase deficiency and hyperinsulinemic hypoglycemia: characterization of a novel mutation and severe dietary protein sensitivity. J Clin Endocrinol Metab 2009; 94: 2221-2225
  8. Pearson ER Boj SF Steele AM Barrett T Stals K Shield JP Ellard S Ferrer J Hattersley AT: Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene. PLoS Med 2007; 4: e118
  9. Sandal T Laborie LB Brusgaard K Eide SA Christesen HB Søvik O Njølstad PR Molven A: The spectrum of ABCC8 mutations in Norwegian patients with congenital hyperinsulinism of infancy. Clin Genet 2009; 75: 440-448
  10. Bennett MJ Russell LK Tokunaga C Narayan SB Tan L Seegmiller A Boriack RL Strauss AW: Reyelike syndrome resulting from novel missense mutations in mitochondrial medium- and short-chain l-3-hydroxy-acyl-CoA dehydrogenase. Mol Genet Metab 2006; 89: 74-79
  11. Vredendaal PJ Van Den Berg IE Stroobants AK Van Der AD Malingre HE Berger R: Structural organization of the human short-chain L-3-hydroxyacyl-CoA dehydrogenase gene. Mamm Genome 1998; 9: 763-768
  12. Flanagan SE Patch AM Locke JM Akcay T Simsek E Alaei M Yekta Z Desai M Kapoor RR Hussain K Ellard S: Genome-wide homozygosity analysis reveals HADH mutations as a common cause of diazoxide-responsive hyperinsulinemic-hypoglycemia in consanguineous pedigrees. J Clin Endocrinol Metab 2011; 96: E498-E502
  13. Van Hove EC Hansen T Dekker JM Reiling E Nijpels G Jorgensen T Borch-Johnsen K Hamid YH Heine RJ Pedersen O Maassen JA T Hart LM: The HADHSC gene encoding short-chain L-3-hydroxyacyl-CoA dehydrogenase (SCHAD) and type 2 diabetes susceptibility: the DAMAGE study. Diabetes 2006; 55: 3193-3196
  14. McCarthy MI: Genomics, type 2 diabetes, and obesity. N Engl J Med 2010; 363: 2339-2350
  15. Molven A Njølstad PR: Role of molecular genetics in transforming diagnosis of diabetes mellitus. Expert Rev Mol Diagn 2011; 11: 313-320
  16. Martens GA Vervoort A Van De Casteele M Stange G Hellemans K Van Thi HV Schuit F Pipeleers D: Specificity in beta cell expression of L-3-hydroxyacyl-CoA dehydrogenase, short chain, and potential role in down-regulating insulin release. J Biol Chem 2007; 282: 21134-21144
  17. Lantz KA Vatamaniuk MZ Brestelli JE Friedman JR Matschinsky FM Kaestner KH: Foxa2 regulates multiple pathways of insulin secretion. J Clin Invest 2004; 114: 512-520
  18. Hardy OT Hohmeier HE Becker TC Manduchi E Doliba NM Gupta RK White P Stoeckert CJ, Jr Matschinsky FM Newgard CB Kaestner KH: Functional genomics of the beta-cell: short-chain 3-hydroxyacyl-coenzyme A dehydrogenase regulates insulin secretion independent of K+ currents. Mol Endocrinol 2007; 21: 765-773
  19. Pepin E Guay C Delghingaro-Augusto V Joly E Madiraju SR Prentki M: Short-chain 3-hydroxyacyl-CoA dehydrogenase is a negative regulator of insulin secretion in response to fuel and non-fuel stimuli in INS832/13 beta-cells. J Diabetes 2010; 2: 157-167
  20. Li C Chen P Palladino A Narayan S Russell LK Sayed S Xiong G Chen J Stokes D Butt YM Jones PM Collins HW Cohen NA Cohen AS Nissim I Smith TJ Strauss AW Matschinsky FM Bennett MJ Stanley CA: Mechanism of hyperinsulinism in short-chain 3-hydroxyacyl-CoA dehydrogenase deficiency involves activation of glutamate dehydrogenase. J Biol Chem 2010; 285: 31806-31818
  21. Hussain K Clayton PT Krywawych S Chatziandreou I Mills P Ginbey DW Geboers AJ Berger R Van Den Berg IE Eaton S: Hyperinsulinism of infancy associated with a novel splice site mutation in the SCHAD gene. J Pediatr 2005; 146: 706-708
  22. Di Candia S Gessi A Pepe G Sogno Valin P Mangano E Chiumello G Gianolli L Proverbio MC Mora S: Identification of a diffuse form of hyperinsulinemic hypoglycemia by 18-fluoro-L-3,4 dihydroxyphenylalanine positron emission tomography/CT in a patient carrying a novel mutation of the HADH gene. Eur J Endocrinol 2009; 160: 1019-1023

Article / Publication Details

First-Page Preview
Abstract of Paper

Published online: February 14, 2012
Cover Date: 2012

Number of Print Pages: 9
Number of Figures: 3
Number of Tables: 1

ISBN: 978-3-8055-9943-6 (Print)
eISBN: 978-3-8055-9944-3 (Online)


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