title: A multi-center comparison of diagnostic methods for the biochemical evaluation of suspected mitochondrial disorders.
abstract: A multicenter comparison of mitochondrial respiratory chain and complex V enzyme activity tests was performed. The average reproducibility of the enzyme assays is 16% in human muscle samples. In a blinded diagnostic accuracy test in patient fibroblasts and SURF1 knock-out mouse muscle, each lab made the correct diagnosis except for two complex I results. We recommend that enzyme activities be evaluated based on ratios, e.g. with complex IV or citrate synthase activity. In spite of large variations in observed enzyme activities, we show that inter-laboratory comparison of patient sample test results is possible by using normalization against a control sample.
authors.affiliation: 774 Nijmegen Centre for Mitochondrial Disorders, Department of Pediatrics, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands. r.rodenburg@cukz.umcn.nl
authors.forename: R J T
authors.initials: RJ
authors.lastname: Rodenburg
authors.forename: G C
authors.initials: GC
authors.lastname: Schoonderwoerd
authors.forename: V
authors.initials: V
authors.lastname: Tiranti
authors.forename: R W
authors.initials: RW
authors.lastname: Taylor
authors.forename: A
authors.initials: A
authors.lastname: Rötig
authors.forename: L
authors.initials: L
authors.lastname: Valente
authors.forename: F
authors.initials: F
authors.lastname: Invernizzi
authors.forename: D
authors.initials: D
authors.lastname: Chretien
authors.forename: L
authors.initials: L
authors.lastname: He
authors.forename: G P B M
authors.initials: GP
authors.lastname: Backx
authors.forename: K J G M
authors.initials: KJ
authors.lastname: Janssen
authors.forename: P F
authors.initials: PF
authors.lastname: Chinnery
authors.forename: H J
authors.initials: HJ
authors.lastname: Smeets
authors.forename: I F
authors.initials: IF
authors.lastname: de Coo
authors.forename: L P
authors.initials: LP
authors.lastname: van den Heuvel
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D019411:Clinical Laboratory Techniques / Q000379:methods*; D003955:Diagnostic Tests, Routine / Q000379:methods*; D004579:Electron Transport; D006801:Humans; D059021:Laboratory Proficiency Testing; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000175:diagnosis*; D025261:Mitochondrial Proton-Translocating ATPases
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D000251:Adenosine Triphosphatases; D025261:Mitochondrial Proton-Translocating ATPases; C020439:oligomycin sensitivity-conferring protein