Disclosure of a putative biosignature for respiratory chain disorders through a metabolomics approach
dc.contributor.author | Smuts, Izelle | |
dc.contributor.author | Van der Westhuizen, Francois Hendrikus | |
dc.contributor.author | Louw, Roan | |
dc.contributor.author | Mienie, Lodewyk J. | |
dc.contributor.author | Engelke, Udo F.H. | |
dc.contributor.author | Wevers, Ron A. | |
dc.contributor.author | Mason, Shayne | |
dc.contributor.author | Koekemoer, Gerhard | |
dc.contributor.author | Reinecke, Carolus J. | |
dc.date.accessioned | 2013-05-08T06:14:40Z | |
dc.date.available | 2013-05-08T06:14:40Z | |
dc.date.issued | 2013-04 | |
dc.description.abstract | The 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.librarian | hj2013 | en_US |
dc.description.librarian | ay2013 | en |
dc.description.sponsorship | The 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.uri | http://www.springerlink.com/content/1573-3882/ | en_US |
dc.identifier.citation | Smuts, 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.issn | 1573-3882 (print) | |
dc.identifier.issn | 1573-3890 (online | |
dc.identifier.other | 10.1007/s11306-012-0455-z | |
dc.identifier.uri | http://hdl.handle.net/2263/21453 | |
dc.language.iso | en | en_US |
dc.publisher | Springer | en_US |
dc.rights | © Springer Science+Business Media, LLC 2012. The original publication is available at www.springerlink.com. | en_US |
dc.subject | Metabolomics | en_US |
dc.subject | Respiratory chain disorders | en_US |
dc.subject | Urinary organic acids | en_US |
dc.subject | Urinary amino acids | en_US |
dc.subject | Data reduction | en_US |
dc.subject | Biosignature | en_US |
dc.subject.lcsh | Pediatric respiratory diseases -- South Africa -- Research | en |
dc.title | Disclosure of a putative biosignature for respiratory chain disorders through a metabolomics approach | en_US |
dc.type | Postprint Article | en_US |