Possible Metabolic Alterations among Autistic Male Children: Clinical and Biochemical Approaches

Autism is a behaviorally defined neurodevelopmental disorder usually diagnosed in early childhood that is characterized by impairment in reciprocal communication and speech, repetitive behaviors, and social withdrawal. Although both genetic and environmental factors are thought to be involved, none have been reproducibly identified. The metabolic phenotype of an individual reflects the influence of endogenous and exogenous factors on genotype. As such, it provides a window through which the interactive impact of genes and environment may be viewed and relevant susceptibility factors identified. Although abnormal methionine metabolism has been associated with other neurologic disorders, these pathways and related polymorphisms have not been evaluated in autistic children. Plasma levels of metabolites in methionine transmethylation and transsulfuration pathways were measured in 80 autistic and 73 control children. In addition, common polymorphic variants known to modulate these metabolic pathways were evaluated in 360 autistic children and 205 controls. The metabolic results indicated that plasma methionine and the ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH), an indicator of methylation capacity, were significantly decreased in the autistic children relative to age-matched controls. In addition, plasma levels of cysteine, glutathione, and the ratio of reduced to oxidized glutathione, an indication of antioxidant capacity and redox homeostasis, were significantly decreased. Differences in allele frequency and/or significant gene-gene interactions were found for relevant genes encoding the reduced folate carrier (RFC 80G > A), transcobalamin II (TCN2 776G > C), catechol-O-methyltransferase (COMT 472G > A), methylenetetrahydrofolate reductase (MTHFR 677C > T and 1298A > C), and glutathione-S-transferase (GST M1). We propose that an increased vulnerability to oxidative stress (endogenous or environmental) may contribute to the development and clinical manifestations of autism. (c) 2006 Wiley-Liss, Inc.

The Short Sensory Profile was used to assess parental report of sensory reactivity across four groups of young children (n = 102). Groups were autism (n = 26), fragile X syndrome (n = 20), developmental disabilities of mixed etiology (n = 32), and typically developing children (n = 24). Groups were comparable on overall mental age (x = 22 months), and clinical groups were comparable on chronological age (x = 31 months). Significant differences were detected at alpha <.01 for tactile sensitivity [F(3,99) = 10.01], taste/smell sensitivity [F(3,99) = 11.63], underreactive/seeks stimulation [F(3,99) = 4.56], auditory filtering [F(3,99) = 19.67], and low energy/weak muscles [F(3,99) = 14.21]. Both children with fragile X syndrome and children with autism had significantly more sensory symptoms overall than the two comparison groups, and children with autism did not differ significantly from children with fragile X syndrome. Both groups were more impaired than developmentally delayed and typically developing children in tactile sensitivity and auditory filtering. Children with autism were more abnormal in responses to taste and smell than all other groups. Children with fragile X syndrome were more abnormal than all other groups in low energy/weak muscles. Sensory reactivity of children with developmental delays was comparable to mental age-matched typically developing toddlers. Correlational analyses indicated that neither overall developmental level nor IQ was related to abnormal sensory reactivity in children with autism or general developmental disorders. However, abnormal sensory reactivity had a significant relationship with overall adaptive behavior.