Rapid analysis of low levels of indolyl-3-acryloylglycine in human urine by high-performance liquid chromatography

Identification of indolyl-3-acryloylglycine in the urine of people with autism

“…The major component extracted from the urine samples was freeze-dried, then reconstituted in acetonitrile : 0.1 % (v}v) aqueous formic acid (18 : 82, v}v) and injected into the mass spectrometer (Mills et al 1998).…”

“…For many years there has been interest in the analysis of body¯uids from people with autism in the search for unusual correlates which could be used as markers for the disorder, and which would provide evidence for a physiological dysfunction (Panksepp 1979;Gillberg 1988;Adrien et al 1989;Knivsberg et al 1990;Shattock et al 1990). As a result of an ongoing programme in this laboratory, screening the urine from people with autism by high-performance liquid chromatography (HPLC), it was noted that there was a particular peak present in all the chromatograms from the sample population (Mills et al 1998). This peak was often present in greatly increased concentrations, based on peak height and area by HPLC, compared with those found in controls.…”

Is the presence of urinary indolyl-3-acryloylglycine associated with autism spectrum disorder?

“…IAG was synthesized by a method adapted from Mills et al (1998), which involved esterification of indole-3-acrylic acid with glycine methyl ester using dicyclohexylcarbodiimide and hydroxybenzotriazole in dichloromethane. In addition, a dideuterated analogue of IAG was synthesized by the same route according to a method by Tilley et al (1994).…”

“…There is no proven association between gluten enteropathy, coeliac disease, and autism with conventional diagnostic methods (McCarthy and Coleman 1979, Pavone et al 1997, Fitzgerald 1999. A research group in Sunderland, UK (Shattock et al 1990(Shattock et al , 1991Mills et al 1998) hypothesized that not only are endogenous opioid peptides implicated in the aetiology of children with autism spectrum disorders (ASDs) but that an excess of indolyl-3acryloylglycine (IAG) in the urine is a marker for autism and the presence of excess opioid peptides. This is supported by analysis of urine samples, which indicates that children with autistic spectrum disorders have high levels of IAG (Anderson et al 2002).…”

Can urinary indolylacroylglycine levels be used to determine whether children with autism will benefit from dietary intervention?

“…IAG:creatinine ratios were calculated to control for variations caused by body mass, urine concentration, and other metabolic factors. IAG was synthesised by a method adapted from (40), which involved esterification of indole-3-acrylic acid with glycine methyl ester using dicyclohexylcarbodiimide and hydroxybenzotriazole in dichloromethane. In addition, a dideuterated analogue of IAG was synthesised by the same route according to a method by Tilley and associates (41).…”