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

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• 作者：Izelle Smuts (1)
  Francois H. van der Westhuizen (2)
  Roan Louw (2)
  Lodewyk J. Mienie (2)
  Udo F. H. Engelke (3)
  Ron A. Wevers (3)
  Shayne Mason (2)
  Gerhard Koekemoer (4)
  Carolus J. Reinecke (2)
  
• 关键词：Metabolomics ; Respiratory chain disorders ; Urinary organic acids ; Urinary amino acids ; Data reduction ; Biosignature
• 刊名：Metabolomics
• 出版年：2013
• 出版时间：April 2013
• 年：2013
• 卷：9
• 期：2
• 页码：379-391
• 全文大小：479KB
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• 作者单位：Izelle Smuts (1)
  Francois H. van der Westhuizen (2)
  Roan Louw (2)
  Lodewyk J. Mienie (2)
  Udo F. H. Engelke (3)
  Ron A. Wevers (3)
  Shayne Mason (2)
  Gerhard Koekemoer (4)
  Carolus J. Reinecke (2)
  
  1. Department of Paediatrics and Child Health, Steve Biko Academic Hospital, University of Pretoria, Pretoria, South Africa
  2. Centre for Human Metabonomics, North-West University, Potchefstroom Campus, Private Bag X6001, Potchefstroom, 2520, South Africa
  3. Laboratory for Genetic, Endocrine and Metabolic Diseases, Department of Laboratory Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  4. Statistical Consultation Services, North-West University, Potchefstroom Campus, Potchefstroom, South Africa
  
• ISSN：1573-3890

文摘

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 sub-sections 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 α-aminoadipic acid) and creatine, was constructed from uni- 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.