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Hexose-6-phosphate Dehydrogenase Deficiency

MedGen UID:
1391920
•Concept ID:
C4330259
•
Disease or Syndrome

Definition

Decreased activity of hexose-6-phosphatase due to autosomal recessive mutation(s) in the H6PD gene. This enzyme is necessary to generate NADPH, a cofactor in the 11-beta-hydroxysteroid dehydrogenase pathway required for conversion of cortisone to cortisol. The condition is characterized by hyperandrogenism as a result of increased adrenocorticotropic hormone stimulation of the adrenal gland due to failure of cortisol-mediated down-regulation, and is clinically indistinguishable from 11-beta HSD type 1 deficiency. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHexose-6-phosphate Dehydrogenase Deficiency

Recent clinical studies

Etiology

A follow-up history of young man with apparent cortisone reductase deficiency (ACRD) - several years after diagnosis.
Zajkowska A, Rydzewska M, Wojtkielewicz K, Pomaski J, Romer T, Bossowski A
Pediatr Endocrinol Diabetes Metab 2017;23(1):42-48. doi: 10.18544/PEDM-23.01.0073. PMID: 29073307
Mutations of the hexose-6-phosphate dehydrogenase gene rarely cause hyperandrogenemic polycystic ovary syndrome.
Qin K, Rosenfield RL
Steroids 2011 Jan;76(1-2):135-9. Epub 2010 Nov 2 doi: 10.1016/j.steroids.2010.10.001. PMID: 21050867Free PMC Article
Hexose-6-phosphate dehydrogenase: a new risk gene for multiple sclerosis.
Alcina A, Ramagopalan SV, Fernández O, Catalá-Rabasa A, Fedetz M, Ndagire D, Leyva L, Arnal C, Delgado C, Lucas M, Izquierdo G, Ebers GC, Matesanz F
Eur J Hum Genet 2010 May;18(5):618-20. Epub 2009 Nov 25 doi: 10.1038/ejhg.2009.213. PMID: 19935835Free PMC Article
Genotypes at 11beta-hydroxysteroid dehydrogenase type 11B1 and hexose-6-phosphate dehydrogenase loci are not risk factors for apparent cortisone reductase deficiency in a large population-based sample.
White PC
J Clin Endocrinol Metab 2005 Oct;90(10):5880-3. Epub 2005 Aug 9 doi: 10.1210/jc.2005-0942. PMID: 16091483

Diagnosis

Novel H6PDH mutations in two girls with premature adrenarche: 'apparent' and 'true' CRD can be differentiated by urinary steroid profiling.
Lavery GG, Idkowiak J, Sherlock M, Bujalska I, Ride JP, Saqib K, Hartmann MF, Hughes B, Wudy SA, De Schepper J, Arlt W, Krone N, Shackleton CH, Walker EA, Stewart PM
Eur J Endocrinol 2013 Feb;168(2):K19-26. Epub 2013 Feb 1 doi: 10.1530/EJE-12-0628. PMID: 23132696Free PMC Article
Altered redox state of luminal pyridine nucleotides facilitates the sensitivity towards oxidative injury and leads to endoplasmic reticulum stress dependent autophagy in HepG2 cells.
Száraz P, Bánhegyi G, Benedetti A
Int J Biochem Cell Biol 2010 Jan;42(1):157-66. Epub 2009 Oct 9 doi: 10.1016/j.biocel.2009.10.004. PMID: 19819344
Physiological roles of 11 beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase.
White PC, Rogoff D, McMillan DR
Curr Opin Pediatr 2008 Aug;20(4):453-7. doi: 10.1097/MOP.0b013e328305e439. PMID: 18622204
11beta-Hydroxysteroid Dehydrogenase Type 1 Regulation by Intracellular Glucose 6-Phosphate Provides Evidence for a Novel Link between Glucose Metabolism and Hypothalamo-Pituitary-Adrenal Axis Function.
Walker EA, Ahmed A, Lavery GG, Tomlinson JW, Kim SY, Cooper MS, Ride JP, Hughes BA, Shackleton CHL, McKiernan P, Elias E, Chou JY, Stewart PM
J Biol Chem 2007 Sep 14;282(37):27030-27036. Epub 2007 Jun 22 doi: 10.1074/jbc.M704144200. PMID: 17588937
Genotypes at 11beta-hydroxysteroid dehydrogenase type 11B1 and hexose-6-phosphate dehydrogenase loci are not risk factors for apparent cortisone reductase deficiency in a large population-based sample.
White PC
J Clin Endocrinol Metab 2005 Oct;90(10):5880-3. Epub 2005 Aug 9 doi: 10.1210/jc.2005-0942. PMID: 16091483

Therapy

A follow-up history of young man with apparent cortisone reductase deficiency (ACRD) - several years after diagnosis.
Zajkowska A, Rydzewska M, Wojtkielewicz K, Pomaski J, Romer T, Bossowski A
Pediatr Endocrinol Diabetes Metab 2017;23(1):42-48. doi: 10.18544/PEDM-23.01.0073. PMID: 29073307
Changing glucocorticoid action: 11β-hydroxysteroid dehydrogenase type 1 in acute and chronic inflammation.
Chapman KE, Coutinho AE, Zhang Z, Kipari T, Savill JS, Seckl JR
J Steroid Biochem Mol Biol 2013 Sep;137:82-92. Epub 2013 Feb 19 doi: 10.1016/j.jsbmb.2013.02.002. PMID: 23435016Free PMC Article

Prognosis

A follow-up history of young man with apparent cortisone reductase deficiency (ACRD) - several years after diagnosis.
Zajkowska A, Rydzewska M, Wojtkielewicz K, Pomaski J, Romer T, Bossowski A
Pediatr Endocrinol Diabetes Metab 2017;23(1):42-48. doi: 10.18544/PEDM-23.01.0073. PMID: 29073307

Clinical prediction guides

Mutations of the hexose-6-phosphate dehydrogenase gene rarely cause hyperandrogenemic polycystic ovary syndrome.
Qin K, Rosenfield RL
Steroids 2011 Jan;76(1-2):135-9. Epub 2010 Nov 2 doi: 10.1016/j.steroids.2010.10.001. PMID: 21050867Free PMC Article
Hexose-6-phosphate dehydrogenase: a new risk gene for multiple sclerosis.
Alcina A, Ramagopalan SV, Fernández O, Catalá-Rabasa A, Fedetz M, Ndagire D, Leyva L, Arnal C, Delgado C, Lucas M, Izquierdo G, Ebers GC, Matesanz F
Eur J Hum Genet 2010 May;18(5):618-20. Epub 2009 Nov 25 doi: 10.1038/ejhg.2009.213. PMID: 19935835Free PMC Article
Altered redox state of luminal pyridine nucleotides facilitates the sensitivity towards oxidative injury and leads to endoplasmic reticulum stress dependent autophagy in HepG2 cells.
Száraz P, Bánhegyi G, Benedetti A
Int J Biochem Cell Biol 2010 Jan;42(1):157-66. Epub 2009 Oct 9 doi: 10.1016/j.biocel.2009.10.004. PMID: 19819344
Lack of Association of the 11beta-hydroxysteroid dehydrogenase type 1 gene 83,557insA and hexose-6-phosphate dehydrogenase gene R453Q polymorphisms with body composition, adrenal androgen production, blood pressure, glucose metabolism, and dementia.
Smit P, Dekker MJ, de Jong FJ, van den Beld AW, Koper JW, Pols HA, Brinkmann AO, de Jong FH, Breteler MM, Lamberts SW
J Clin Endocrinol Metab 2007 Jan;92(1):359-62. Epub 2006 Oct 24 doi: 10.1210/jc.2006-1349. PMID: 17062770
A study of the hexose-6-phosphate dehydrogenase gene R453Q and 11beta-hydroxysteroid dehydrogenase type 1 gene 83557insA polymorphisms in the polycystic ovary syndrome.
San Millán JL, Botella-Carretero JI, Alvarez-Blasco F, Luque-Ramírez M, Sancho J, Moghetti P, Escobar-Morreale HF
J Clin Endocrinol Metab 2005 Jul;90(7):4157-62. Epub 2005 Apr 12 doi: 10.1210/jc.2004-1523. PMID: 15827106

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