Quantitation of plasma thiamine, related metabolites and plasma protein oxidative damage markers in children with autism spectrum disorder and healthy controls.
OBJECTIVE
To assess thiamine and related metabolite status by analysis of plasma and urine in autistic children and healthy controls, correlations to clinical characteristics and link to plasma protein markers of oxidative damage.


METHODS
27 children with autism (21 males and 6 females) and 21 (15 males and 6 females) age-matched healthy control children were recruited. The concentration of thiamine and related phosphorylated metabolites in plasma and urine and plasma protein content of dityrosine, N-formylkynurenine and 3-nitrotyrosine was determined.


RESULTS
Plasma thiamine and thiamine monophosphate concentrations were similar in both study groups (median [lower-upper quartile]): autistic children - 6.60 nM (4.48-8.91) and 7.00 nM (5.51-8.55), and healthy controls - 6.82 nM (4.47-7.02) and 6.82 nM (5.84-8.91), respectively. Thiamine pyrophosphate (TPP) was decreased 24% in autistic children compared to healthy controls: 6.82 nM (5.81-8.52) versus 9.00 nM (8.41-10.71), p < .01. Urinary excretion of thiamine and fractional renal clearance of thiamine did not change between the groups. No correlation was observed between clinical markers and the plasma and urine thiamine concentration. Plasma protein dityrosine content was increased 88% in ASD. Other oxidative markers were unchanged.


CONCLUSIONS
Autistic children had normal plasma and urinary thiamine levels whereas plasma TPP concentration was decreased. The latter may be linked to abnormal tissue handling and/or absorption from gut microbiota of TPP which warrants further investigation. Increased plasma protein dityrosine may reflect increased dual oxidase activity in response to change in mucosal immunity and host-microbe homeostasis.
a Warwick Medical School, Clinical Sciences Research Laboratories , University of Warwick, University Hospital Coventry , Coventry , UK.
Attia
A
Anwar
b Department of Experimental, Diagnostic and Specialty Medicine , School of Medicine, University of Bologna , Bologna , Italy.|c Don Carlo Gnocchi Foundation ONLUS, IRCCS "S. Maria Nascente" , Milan , Italy.
Marina
M
Marini
b Department of Experimental, Diagnostic and Specialty Medicine , School of Medicine, University of Bologna , Bologna , Italy.|c Don Carlo Gnocchi Foundation ONLUS, IRCCS "S. Maria Nascente" , Milan , Italy.
Provvidenza Maria
PM
Abruzzo
b Department of Experimental, Diagnostic and Specialty Medicine , School of Medicine, University of Bologna , Bologna , Italy.|c Don Carlo Gnocchi Foundation ONLUS, IRCCS "S. Maria Nascente" , Milan , Italy.
Alessandra
A
Bolotta
b Department of Experimental, Diagnostic and Specialty Medicine , School of Medicine, University of Bologna , Bologna , Italy.
Alessandro
A
Ghezzo
d Child Neurology and Psychiatry Unit , IRCCS Institute of Neurological Sciences , Bologna , Italy.
Paola
P
Visconti
a Warwick Medical School, Clinical Sciences Research Laboratories , University of Warwick, University Hospital Coventry , Coventry , UK.|e Warwick Systems Biology, Clinical Sciences Research Laboratories , University of Warwick, University Hospital Coventry , Coventry , UK.
Paul J
PJ
Thornalley
e Warwick Systems Biology, Clinical Sciences Research Laboratories , University of Warwick, University Hospital Coventry , Coventry , UK.
Naila
N
Rabbani
D000067877:Autism Spectrum Disorder / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D018384:Oxidative Stress; D013831:Thiamine / Q000378:metabolism*
D013831:Thiamine
Autism; dityrosine; thiamine; thiamine pyrophosphate