Journal of Inherited Metabolic Disease

, Volume 32, Issue 2, pp 135–142 | Cite as

l-2-Hydroxyglutaric aciduria, a disorder of metabolite repair

  • E. Van Schaftingen
  • R. Rzem
  • M. Veiga-da-Cunha
Ssiem Symposium 2008


The neurometabolic disorder l-2-hydroxyglutaric aciduria is caused by mutations in a gene present on chromosome 14q22.1 and encoding l-2-hydroxyglutarate dehydrogenase. This FAD-linked mitochondrial enzyme catalyses the irreversible conversion of l-2-hydroxyglutarate to alpha-ketoglutarate. The formation of l-2-hydroxyglutarate results from a side-activity of mitochondrial l-malate dehydrogenase, the enzyme that interconverts oxaloacetate and l-malate, but which also catalyses, very slowly, the NADH-dependent conversion of alpha-ketoglutarate to l-2-hydroxyglutarate. l-2-Hydroxyglutarate has no known physiological function in eukaryotes and most prokaryotes. Its accumulation is toxic to the mammalian brain, causing a leukoencephalopathy and increasing the susceptibility to develop tumours. l-2-Hydroxyglutaric aciduria appears to be the first disease of ‘metabolite repair’.


Saccharopine Neurometabolic Disorder Dicarboxylic Aciduria Pyruvate Carboxylase Deficiency Riboflavin Supplement 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



l-2-hydroxyglutarate dehydrogenase gene



Work in the authors’ laboratory is supported by the Interuniversity Attraction Pole Programme, Belgian Science Policy (network P6/05), the Fonds de la Recherche Scientifique Médicale, the Actions de Recherche Concertées of the French Community of Belgium, and by a grant of Asco industries. M.V.D.C. is Chercheur Qualifié of the Fonds National de la Recherche Scientifique.


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Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • E. Van Schaftingen
    • 1
    • 2
  • R. Rzem
    • 1
  • M. Veiga-da-Cunha
    • 1
  1. Duve InstituteUniversité catholique de LouvainBrusselsBelgium
  2. 2.BrusselsBelgium

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