Abstract
Although developmental delays affect learning, language, and behavior, some evidence suggests the presence of disturbances in metabolism are associated with psychiatric disorders. Here, the plasma metabolic phenotype of children with autism spectrum disorder (ASD, n = 167), idiopathic-developmental delay (i-DD, n = 51), and Down syndrome (DS, n = 31), as compared to typically developed (TD, n = 193) controls was investigated in a subset of children from the case–control Childhood Autism Risk from Genetics and the Environment (CHARGE) Study. Metabolome profiles were obtained using nuclear magnetic resonance spectroscopy and analyzed in an untargeted manner. Forty-nine metabolites were identified and quantified in each sample that included amino acids, organic acids, sugars, and other compounds. Multiple linear regression analysis revealed significant associations between 11 plasma metabolites and neurodevelopmental outcome. Despite the varied origins of these developmental disabilities, we observed similar perturbation in one-carbon metabolism pathways among DS and ASD cases. Similarities were also observed in the DS and i-DD cases in the energy-related tricarboxylic acid cycle. Other metabolites and pathways were uniquely associated with DS or ASD. By comparing metabolic signatures between these conditions, the current study expands on extant literature demonstrating metabolic alterations associated with developmental disabilities and provides a better understanding of overlapping vs specific biological perturbations associated with these disorders.
Highlights
It is estimated that about one in six children between the ages of 3 and 17 years in the United States have one or more developmental disability[1]
I-delay but not ASD (DD) and Down syndrome (DS) children were more likely to be female than were typically developed (TD) children
This was because the TD sex distribution was matched to the projected autism spectrum disorder (ASD) sex ratio of 4:1, but the DD group was not matched
Summary
It is estimated that about one in six children between the ages of 3 and 17 years in the United States have one or more developmental disability[1]. Developmental delays may impact day-to-day functioning, and usually last throughout a person’s lifetime. Some developmental delays have a known cause, such as the atypical cell division resulting in an extra portion of chromosome 21 (HSA21) that results in Down syndrome (DS). Most developmental disabilities are thought to be caused by a combination of factors that include genetics and/or environment. One such example is autism spectrum disorder (ASD), which has been linked with genetic mutations and environmental exposures and has a complex gene-environmental origin[2,3]. ASD has been associated with increased oxidative stress[5,6], decreased methylation capacity[6,7], impaired sulfur metabolism[8,9], gut microbiome dysbiosis[10,11], and altered energy metabolism[12,13]
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