Smuts, IzelleVan der Westhuizen, Francois HendrikusLouw, RoanMienie, Lodewyk J.Engelke, Udo F.H.Wevers, Ron A.Mason, ShayneKoekemoer, GerhardReinecke, Carolus J.2013-05-082013-05-082013-04Smuts, I, Van der Westhuizen, FH, Louw, R, Mienie, LJ, Engelke, UFH, Wevers, RA, Mason, S, Koekemoer, G & Reinecke, CJ 2013, 'Disclosure of a putative biosignature for respiratory chain disorders through a metabolomics approach', Metabolomics, vol. 9, no. 2, pp. 379-391.1573-3882 (print)1573-3890 (online10.1007/s11306-012-0455-zhttp://hdl.handle.net/2263/21453The diagnosis of respiratory chain deficiencies (RCDs) is complicated and the need for a diagnostic biomarker or biosignature has been widely expressed. In this study, the metabolic profile of a selected group of 29 RCD patients,with a predominantly muscle disease phenotype, and 22 controls were investigated using targeted and untargeted analyses of three sub-sections of the human metabolome, including urinary organic acids and amino acids [measured by gas chromatography–mass spectrometry (GC–MS)], as well as acylcarnitines (measured by electrospray ionization tandem MS). Although MS technologies are highly sensitive and selective, they are restrictive by being applied only to subsections of the metabolome; an untargeted nuclear magnetic resonance (NMR) spectroscopy approach was therefore also included. After data reduction and pre-treatment, a biosignature comprising six organic acids (lactic, succinic, 2-hydroxyglutaric, 3-hydroxyisobutyric, 3-hydroxyisovaleric and 3-hydroxy-3-methylglutaric acids), six amino acids (alanine, glycine, glutamic acid, serine, tyrosine and a-aminoadipic acid) and creatine,was constructed fromuni- and multivariate statistical analyses and verified by cross-validation. The results presented here provide the first proof-of-concept that the metabolomics approach is capable of defining a biosignature for RCDs. We postulate that the composite of organic acids & amino acids[creatine[betaine[carnitines represents the basic biosignature for RCDs. Validated through a prospective study, this could offer an improved ability to assign individual patients to a group with defined RCD characteristics and improve case selection for biopsy procedures, especially in infants and children.en© Springer Science+Business Media, LLC 2012. The original publication is available at www.springerlink.com.MetabolomicsRespiratory chain disordersUrinary organic acidsUrinary amino acidsData reductionBiosignaturePediatric respiratory diseases -- South Africa -- ResearchPostprint Article