Abstract:
Metabolomic analysis of the urinary organic acids from 39 selected children with defined respiratory chain
deficiencies (RCDs) was performed using untargeted gas chromatography–mass spectrometry, revealing the
presence of 255 endogenous and 46 exogenous substances. Variable reduction identified 92 variables from the
endogenous substances, which could be analysed by univariate and multivariate statistical methods. Using
these methods, no characteristic organic acid biomarker profile could be defined of practical value for diagnostic
purposes for complex I (CI), complex III (CIII) and multiple complex (CM) deficiencies. The statistical procedures
used did, however, disclose 24 metabolites that were practical highly (d > 0.75) and statistically (p < 0.05)
significant for the combined and clinically closely related group of RCDs. Several of these metabolites occur in
single enzyme inherited metabolic diseases, but most were not previously reported to be linked to the metabolic
perturbations that are due to RCDs. Ultimately, we constructed a global metabolic profile of carbohydrate, amino
acid and fatty acid catabolism, illuminating the diverse and complex biochemical consequences of these
disorders. This metabolomics investigation disclosed a metabolite profile that has the potential to define an extended and characteristic biosignature for RCDs and the development of a non-invasive screening procedure
for these disorders.
