Indolyl-3-acryloylglycine (IAG) is a putative diagnostic urinary marker for autism spectrum disorders

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.

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.

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.

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.