title: GC-MS-based urine metabolic profiling of autism spectrum disorders.
abstract: Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders resulting from multiple factors. Diagnosis is based on behavioural and developmental signs detected before 3 years of age, and there is no reliable biological marker. The purpose of this study was to evaluate the value of gas chromatography combined with mass spectroscopy (GC-MS) associated with multivariate statistical modeling to capture the global biochemical signature of autistic individuals. GC-MS urinary metabolic profiles of 26 autistic and 24 healthy children were obtained by liq/liq extraction, and were or were not subjected to an oximation step, and then were subjected to a persilylation step. These metabolic profiles were then processed by multivariate analysis, in particular orthogonal partial least-squares discriminant analysis (OPLS-DA, R(2)Y(cum) = 0.97, Q(2)(cum) = 0.88). Discriminating metabolites were identified. The relative concentrations of the succinate and glycolate were higher for autistic than healthy children, whereas those of hippurate, 3-hydroxyphenylacetate, vanillylhydracrylate, 3-hydroxyhippurate, 4-hydroxyphenyl-2-hydroxyacetate, 1H-indole-3-acetate, phosphate, palmitate, stearate, and 3-methyladipate were lower. Eight other metabolites, which were not identified but characterized by a retention time plus a quantifier and its qualifier ion masses, were found to differ between the two groups. Comparison of statistical models leads to the conclusion that the combination of data obtained from both derivatization techniques leads to the model best discriminating between autistic and healthy groups of children.
authors.affiliation: INSERM U930, Equipe neurogénétique et neurométabolomique, CHRU de Tours, Hôpital Bretonneau, Université François-Rabelais, 10 Bv Tonnellé, 37044 Tours, France. patrick.emond@univ-tours.fr
authors.forename: Patrick
authors.initials: P
authors.lastname: Emond
authors.forename: Sylvie
authors.initials: S
authors.lastname: Mavel
authors.forename: Nacima
authors.initials: N
authors.lastname: Aïdoud
authors.forename: Lydie
authors.initials: L
authors.lastname: Nadal-Desbarats
authors.forename: Frédéric
authors.initials: F
authors.lastname: Montigny
authors.forename: Frédérique
authors.initials: F
authors.lastname: Bonnet-Brilhault
authors.forename: Catherine
authors.initials: C
authors.lastname: Barthélémy
authors.forename: Marc
authors.initials: M
authors.lastname: Merten
authors.forename: Pierre
authors.initials: P
authors.lastname: Sarda
authors.forename: Frédéric
authors.initials: F
authors.lastname: Laumonnier
authors.forename: Patrick
authors.initials: P
authors.lastname: Vourc'h
authors.forename: Hélène
authors.initials: H
authors.lastname: Blasco
authors.forename: Christian R
authors.initials: CR
authors.lastname: Andres
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D005591:Chemical Fractionation; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000652:urine*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D008297:Male; D055432:Metabolomics / Q000379:methods*