title: Indolyl-3-acryloylglycine (IAG) is a putative diagnostic urinary marker for autism spectrum disorders.
abstract: BACKGROUND
  Autism is a heterogeneous pervasive developmental disorder with a poorly defined aetiology and pathophysiology. There are indications that the incidence of the disease is rising but still no definitive diagnostic biochemical markers have been isolated. Here we have addressed the hypothesis that urinary levels of trans -indolyl-3-acryloylglycine (IAG) are abnormal in patients diagnosed with autism spectrum disorders (ASD) compared to age-matched controls.
  
  
  METHODS
  Urine samples were collected on an opportunistic basis and analysed for IAG concentration (normalised against creatinine content to account for changes in urinary volume) using reversed phase HPLC with UV detection.
  
  
  RESULTS
  Statistical analysis (Mann-Whitney tests) showed highly significant increases (p=0.0002) in the levels of urinary IAG in the ASD group (median 942 microV per mmol/L of creatinine [interquartile range 521-1729], n=22) compared to asymptomatic controls (331 [163-456], n=18). Detailed retrospective analysis showed that gender (boys 625 microV per mmol/L of creatinine [294-1133], n=29; girls 460 [282-1193], n=11: P=0.79) and age (control donor median 10 years [8-14], n=15; ASD median 9 years [7-11] n=22: P=0.54) were not significantly correlated with IAG levels in this non-blinded volunteer study.
  
  
  CONCLUSIONS
  Our results strongly suggest that urinary titres of IAG may constitute an objective diagnostic indicator for ASD. Mechanisms for the involvement of IAG in ASD are discussed together with future strategies to address its specificity.
authors.affiliation: Sunderland General Hospital, Sunderland, UK.
authors.forename: Gillian
authors.initials: G
authors.lastname: Bull
authors.forename: Paul
authors.initials: P
authors.lastname: Shattock
authors.forename: Paul
authors.initials: P
authors.lastname: Whiteley
authors.forename: Roz
authors.initials: R
authors.lastname: Anderson
authors.forename: Paul W
authors.initials: PW
authors.lastname: Groundwater
authors.forename: John W
authors.initials: JW
authors.lastname: Lough
authors.forename: George
authors.initials: G
authors.lastname: Lees
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001321:Autistic Disorder / Q000175:diagnosis* / Q000235:genetics / Q000652:urine*; D001681:Biological Assay; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D003401:Creatine / Q000652:urine; D003404:Creatinine / Q000652:urine; D002658:Developmental Disabilities / Q000235:genetics; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000652:urine*; D006801:Humans; D008297:Male; D012680:Sensitivity and Specificity; D014466:Ultraviolet Rays
chemical_list: C001807:indolylacryloylglycine; D003404:Creatinine; D003401:Creatine; D005998:Glycine