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Deficiency in SLC25A1, encoding the mitochondrial citrate carrier, causes combined D-2- and L-2-hydroxyglutaric aciduria.

Authors: Nota, Benjamin  Struys, Eduard A  Pop, Ana  Jansen, Erwin E  Fernandez Ojeda, Matilde R  Kanhai, Warsha A  Kranendijk, Martijn  van Dooren, Silvy J M  Bevova, Marianna R  Sistermans, Erik A  Nieuwint, Aggie W M  Barth, Magalie  Ben-Omran, Tawfeg  Hoffmann, Georg F  de Lonlay, Pascale  McDonald, Marie T  Meberg, Alf  Muntau, Ania C  Nuoffer, Jean-Marc  Parini, Rossella  Read, Marie-Hélène  Renneberg, Axel  Santer, René  Strahleck, Thomas  van Schaftingen, Emile  van der Knaap, Marjo S  Jakobs, Cornelis  Salomons, Gajja S 
Citation: Nota B, etal., Am J Hum Genet. 2013 Apr 4;92(4):627-31. doi: 10.1016/j.ajhg.2013.03.009.
Pubmed: (View Article at PubMed) PMID:23561848
DOI: Full-text: DOI:10.1016/j.ajhg.2013.03.009

The Krebs cycle is of fundamental importance for the generation of the energetic and molecular needs of both prokaryotic and eukaryotic cells. Both enantiomers of metabolite 2-hydroxyglutarate are directly linked to this pivotal biochemical pathway and are found elevated not only in several cancers, but also in different variants of the neurometabolic disease 2-hydroxyglutaric aciduria. Recently we showed that cancer-associated IDH2 germline mutations cause one variant of 2-hydroxyglutaric aciduria. Complementary to these findings, we now report recessive mutations in SLC25A1, the mitochondrial citrate carrier, in 12 out of 12 individuals with combined D-2- and L-2-hydroxyglutaric aciduria. Impaired mitochondrial citrate efflux, demonstrated by stable isotope labeling experiments and the absence of SLC25A1 in fibroblasts harboring certain mutations, suggest that SLC25A1 deficiency is pathogenic. Our results identify defects in SLC25A1 as a cause of combined D-2- and L-2-hydroxyglutaric aciduria.


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RGD Object Information
RGD ID: 13506826
Created: 2018-02-20
Species: All species
Last Modified: 2018-02-20
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.