Mechanism of nitrogen metabolism-related parameters and enzyme activities in the pathophysiology of autism

Background: There is evidence that impaired metabolism play an important role in the etiology of many neuropsychiatric disorders. Although this has not been investigated to date, several recent studies proposed that nitrogen metabolism-related parameters may have a pathophysiological role in autism. Methods: The study enrolled 20 Saudi boys with autism aged 4 to 12 years and 20 healthy controls matched for age and gender. Levels of creatine, urea, ammonia, gamma-aminobutyric acid (GABA), glutamate: glutamine (Glu: Gln) ratio, and enzymatic activities of glutamate dehydrogenase, 5'-nucleotidase, and adenosine deaminase (ADA) were determined in plasma samples from both groups. Results: We found a significant elevation of creatine, 5'-nucleotidase, GABA, and glutamic acid and a significant decrease in the enzymatic activity of ADA and glutamine level in patients with autism compared with healthy controls. The most significant variation between the two groups was found in the Glu: Gln ratio. Conclusion: A raised Glu: Gln ratio together with positive correlations in creatine, GABA, and 5'-nucleotidase levels could contribute to the pathophysiology of autism, and might be useful diagnostic markers. The mechanism through which these parameters might be related to autism is discussed in detail.