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

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.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.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.Autism is a complex disorder that is heterogeneous in nature, with varying degrees of severity, and for which no specific biological marker has been identified. A recent epidemiological study in Saudi Arabia established the autism prevalence at 6:1000 (Talat; unpublished data, personal communication). The increasing prevalence of autism is raising public-health concerns [1]. As indicated by several biological parameters, a hallmark of autism is its substantial heterogeneity. Although the core deficits may fall in the similar domains, no two people with autism have exactly the same profile. Such a wide range of clinical features makes the diagnosis and treatment of autism very challenging. The overlapping of different biological and genetic etiologies and the individual variations in patients with autism makes it difficult to establish unified diagnostic biomarkers and therapeutic strategies [2,3].Autism involves many metabolic derangements, such as those involving the trans-sulfation pathway that synthesizes cystei