Disclosure of a putative biosignature for respiratory chain disorders through a metabolomics approach

dc.contributor.authorSmuts, Izelle
dc.contributor.authorVan der Westhuizen, Francois Hendrikus
dc.contributor.authorLouw, Roan
dc.contributor.authorMienie, Lodewyk J.
dc.contributor.authorEngelke, Udo F.H.
dc.contributor.authorWevers, Ron A.
dc.contributor.authorMason, Shayne
dc.contributor.authorKoekemoer, Gerhard
dc.contributor.authorReinecke, Carolus J.
dc.date.accessioned2013-05-08T06:14:40Z
dc.date.available2013-05-08T06:14:40Z
dc.date.issued2013-04
dc.description.abstractThe 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_US
dc.description.librarianhj2013en_US
dc.description.librarianay2013en
dc.description.sponsorshipThe South African Department of Science and Technology, North-West University and S.W. Mason is a recipient of a Vrije Universiteit (VU) Amsterdam-National Research Foundation (NRF)- Desmond Tutu PhD Fellowship.en_US
dc.description.urihttp://www.springerlink.com/content/1573-3882/en_US
dc.identifier.citationSmuts, 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.en_US
dc.identifier.issn1573-3882 (print)
dc.identifier.issn1573-3890 (online
dc.identifier.other10.1007/s11306-012-0455-z
dc.identifier.urihttp://hdl.handle.net/2263/21453
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.rights© Springer Science+Business Media, LLC 2012. The original publication is available at www.springerlink.com.en_US
dc.subjectMetabolomicsen_US
dc.subjectRespiratory chain disordersen_US
dc.subjectUrinary organic acidsen_US
dc.subjectUrinary amino acidsen_US
dc.subjectData reductionen_US
dc.subjectBiosignatureen_US
dc.subject.lcshPediatric respiratory diseases -- South Africa -- Researchen
dc.titleDisclosure of a putative biosignature for respiratory chain disorders through a metabolomics approachen_US
dc.typePostprint Articleen_US

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