Combined 1H-NMR and 1H-13C HSQC-NMR to improve urinary screening in autism spectrum disorders.
Autism spectrum disorders (ASD) are neurodevelopmental diseases with complex genetic and environmental etiological factors. Although genetic causes play a significant part in the etiology of ASD, metabolic disturbances may also play a causal role or modulate the clinical features of ASD. The number of ASD studies involving metabolomics is increasing, and sometime with conflicting findings. We assessed the metabolomics profiling of urine samples to determine a comprehensive biochemical signature of ASD. Furthermore, to date no study has combined metabolic profiles obtained from different analytical techniques to distinguish patient with ASD from healthy individuals. We obtained (1)H-NMR spectra and 2D (1)H-(13)C HSQC NMR spectra from urine samples of patients with ASD or healthy controls. We analyzed these spectra by multivariate statistical data analysis. The OPLS-DA model obtained from (1)H NMR spectra showed a good discrimination between ASD samples and non-ASD samples (R(2)Y(cum) = 0.70 and Q(2) = 0.51). Combining the (1)H NMR spectra and the 2D (1)H-(13)C HSQC NMR spectra increased the overall quality and predictive value of the OPLS-DA model (R(2)Y(cum) = 0.84 and Q(2) = 0.71), leading to a better sensitivity and specificity. Urinary excretion of succinate, glutamate and 3-methyl-histidine differed significantly between ASD and non-ASD samples. Urinary screening of children with neurodevelopmental disorders by combining NMR spectroscopies (1D and 2D) in multivariate analysis is a better sensitive and a straightforward method that could help the diagnosis ASD.
Equipe neurogénétique et neurométabolomique INSERM U930, Université François Rabelais, PPF "Analyses des Systèmes Biologiques", UFR de Médecine, 10 BlvdTonnellé, 37044 Tours Cedex 9, 37000 Tours, France. nadal@med.univ-tours.fr.
Lydie
L
Nadal-Desbarats
Nacima
N
Aïdoud
Patrick
P
Emond
Hélène
H
Blasco
Isabelle
I
Filipiak
Pierre
P
Sarda
Frédérique
F
Bonnet-Brilhault
Sylvie
S
Mavel
Christian R
CR
Andres
D002648:Child; D002659:Child Development Disorders, Pervasive / Q000378:metabolism / Q000652:urine*; D005260:Female; D006801:Humans; D008297:Male; D055432:Metabolomics / Q000379:methods*; D015999:Multivariate Analysis; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods*; D016482:Urinalysis / Q000379:methods; D014556:Urine / Q000737:chemistry