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D2HGDH gene

D-2-hydroxyglutarate dehydrogenase

Normal Function

The D2HGDH gene provides instructions for making an enzyme called D-2-hydroxyglutarate dehydrogenase. This enzyme is found in mitochondria, which are the energy-producing centers within cells. Within mitochondria, the enzyme participates in reactions that produce energy for cell activities. Specifically, D-2-hydroxyglutarate dehydrogenase converts a compound called D-2-hydroxyglutarate to another compound called 2-ketoglutarate. A series of additional enzymes further process 2-ketoglutarate to produce energy.

Health Conditions Related to Genetic Changes

2-hydroxyglutaric aciduria

Researchers have identified more than 30 D2HGDH gene mutations that cause a type of 2-hydroxyglutaric aciduria known as D-2-hydroxyglutaric aciduria (D-2-HGA) type I. This condition has a variety of signs and symptoms that result primarily from progressive damage to the brain beginning early in life.

Some D2HGDH gene mutations change single protein building blocks (amino acids) in the D-2-hydroxyglutarate dehydrogenase enzyme, which likely impairs its function. Other mutations lead to the production of an abnormally short, nonfunctional version of the enzyme. With a shortage of functional enzyme, D-2-hydroxyglutarate is not broken down but instead builds up in cells. At high levels, this compound can damage cells and lead to cell death. Brain cells appear to be the most vulnerable to the toxic effects of this compound, which may explain why the signs and symptoms of D-2-HGA type I primarily involve the brain.

More About This Health Condition

Other Names for This Gene

  • 2-hydroxypentanedioic acid
  • D2HGD
  • FLJ42195
  • MGC25181

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases


  • Kranendijk M, Struys EA, Gibson KM, Wickenhagen WV, Abdenur JE, Buechner J, Christensen E, de Kremer RD, Errami A, Gissen P, Gradowska W, Hobson E, Islam L, Korman SH, Kurczynski T, Maranda B, Meli C, Rizzo C, Sansaricq C, Trefz FK, Webster R, Jakobs C, Salomons GS. Evidence for genetic heterogeneity in D-2-hydroxyglutaric aciduria. Hum Mutat. 2010 Mar;31(3):279-83. doi: 10.1002/humu.21186. Citation on PubMed
  • Kranendijk M, Struys EA, Salomons GS, Van der Knaap MS, Jakobs C. Progress in understanding 2-hydroxyglutaric acidurias. J Inherit Metab Dis. 2012 Jul;35(4):571-87. doi: 10.1007/s10545-012-9462-5. Epub 2012 Mar 6. Citation on PubMed or Free article on PubMed Central
  • Struys EA, Korman SH, Salomons GS, Darmin PS, Achouri Y, van Schaftingen E, Verhoeven NM, Jakobs C. Mutations in phenotypically mild D-2-hydroxyglutaric aciduria. Ann Neurol. 2005 Oct;58(4):626-30. doi: 10.1002/ana.20559. Citation on PubMed
  • Struys EA, Salomons GS, Achouri Y, Van Schaftingen E, Grosso S, Craigen WJ, Verhoeven NM, Jakobs C. Mutations in the D-2-hydroxyglutarate dehydrogenase gene cause D-2-hydroxyglutaric aciduria. Am J Hum Genet. 2005 Feb;76(2):358-60. doi: 10.1086/427890. Epub 2004 Dec 17. Citation on PubMed or Free article on PubMed Central
  • Struys EA. D-2-Hydroxyglutaric aciduria: unravelling the biochemical pathway and the genetic defect. J Inherit Metab Dis. 2006 Feb;29(1):21-9. doi: 10.1007/s10545-006-0317-9. Citation on PubMed

The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.