title: Inborn errors of the Krebs cycle: a group of unusual mitochondrial diseases in human.
abstract: Krebs cycle disorders constitute a group of rare human diseases which present an amazing complexity considering our current knowledge on the Krebs cycle function and biogenesis. Acting as a turntable of cell metabolism, it is ubiquitously distributed in the organism and its enzyme components encoded by supposedly typical house-keeping genes. However, the investigation of patients presenting specific defects of Krebs cycle enzymes, resulting from deleterious mutations of the considered genes, leads to reconsider this simple envision by revealing organ-specific impairments, mostly affecting neuromuscular system. This often leaves aside organs the metabolism of which strongly depends on mitochondrial energy metabolism as well, such as heart, kidney or liver. Additionally, in some patients, a complex pattern of tissue-specific enzyme defect was also observed. The lack of functional additional copies of Krebs cycle genes suggests that the complex expression pattern should be ascribed to tissue-specific regulations of transcriptional and/or translational activities, together with a variable cell adaptability to Krebs cycle functional defects.
authors.affiliation: Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U-393, Hôpital des Enfants-Malades, Paris, France. rustin@necker.fr
authors.forename: P
authors.initials: P
authors.lastname: Rustin
authors.forename: T
authors.initials: T
authors.lastname: Bourgeron
authors.forename: B
authors.initials: B
authors.lastname: Parfait
authors.forename: D
authors.initials: D
authors.lastname: Chretien
authors.forename: A
authors.initials: A
authors.lastname: Munnich
authors.forename: A
authors.initials: A
authors.lastname: Rötig
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002952:Citric Acid Cycle / Q000235:genetics*; D005649:Fumarate Hydratase / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D007223:Infant; D007655:Ketoglutarate Dehydrogenase Complex / Q000172:deficiency* / Q000235:genetics; D008661:Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics* / Q000652:urine; D009154:Mutation; D013385:Succinate Dehydrogenase / Q000172:deficiency* / Q000235:genetics
chemical_list: D007655:Ketoglutarate Dehydrogenase Complex; D013385:Succinate Dehydrogenase; D005649:Fumarate Hydratase