Heterozygous somatic mutations in the genes encoding isocitrate dehydrogenase-1 and -2 (IDH1 and IDH2) were recently discovered in human neoplastic disorders. These mutations disable the enzymes' normal ability to convert isocitrate to 2-ketoglutarate (2-KG) and confer on the enzymes a new function: the ability to convert 2-KG to d-2-hydroxyglutarate (D-2-HG). We have detected heterozygous germline mutations in IDH2 that alter enzyme residue Arg(140) in 15 unrelated patients with d-2-hydroxyglutaric aciduria (D-2-HGA), a rare neurometabolic disorder characterized by supraphysiological levels of D-2-HG. These findings provide additional impetus for investigating the role of D-2-HG in the pathophysiology of metabolic disease and cancer.
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Bibliographic reference
Kranendijk, Martijn ; Struys, Eduard A ; Van Schaftingen, Emile ; Gibson, K Michael ; Kanhai, Warsha A ; et. al. IDH2 mutations in patients with D-2-hydroxyglutaric aciduria. In: Science, Vol. 330, no. 6002, p. 336 (2010)
