IDH2, encoding mitochondrial isocitrate dehydrogenase 2 has been shown last year to be mutated in various tumors, providing a new link between intermediary metabolism and cancer. This prompted Martijn Kranendijk et al. to study this gene in patients with D-2-Hydroxyglutaric Aciduria. While some are asymptomatic, others have developmental delay, epilepsy, hypotonia, cardiomyopathy and dysmorphic features.Â A few have mutations in D2HGDH, encoding D-2-hydroxyglutarate dehydrogenase. The group sequenced IDH2 in 17 patients without D2HGDH mutations, and found germline IDH2 mutations in 15 of 17 patients (Kranendijk et al., 2010, Science 330:336). Another inborn error of metabolism caused by mutations in a mitochondrial protein is primary hyperoxaluria type III caused by mutations in DHDPSL. The gene encodes a protein which probably synthesizes glyoxalate in the mitochondria, and activating mutations would increase glyoxalate and then oxalate accumulation (Belostotsky et al., 2010, Am J Hum Genet 87:392-9).
Philippe Campeau, MD