Abstract
BackgroundPrevious research studies have demonstrated abnormalities in the metabolism of mothers of young children with autism.MethodsMetabolic analysis was performed on blood samples from 30 mothers of young children with Autism Spectrum Disorder (ASD-M) and from 29 mothers of young typically-developing children (TD-M). Targeted metabolic analysis focusing on the folate one-carbon metabolism (FOCM) and the transsulfuration pathway (TS) as well as broad metabolic analysis were performed. Statistical analysis of the data involved both univariate and multivariate statistical methods.ResultsUnivariate analysis revealed significant differences in 5 metabolites from the folate one-carbon metabolism and the transsulfuration pathway and differences in an additional 48 metabolites identified by broad metabolic analysis, including lower levels of many carnitine-conjugated molecules.Multivariate analysis with leave-one-out cross-validation allowed classification of samples as belonging to one of the two groups of mothers with 93% sensitivity and 97% specificity with five metabolites. Furthermore, each of these five metabolites correlated with 8–15 other metabolites indicating that there are five clusters of correlated metabolites. In fact, all but 5 of the 50 metabolites with the highest area under the receiver operating characteristic curve were associated with the five identified groups. Many of the abnormalities appear linked to low levels of folate, vitamin B12, and carnitine-conjugated molecules.ConclusionsMothers of children with ASD have many significantly different metabolite levels compared to mothers of typically developing children at 2–5 years after birth.
Highlights
Previous research studies have demonstrated abnormalities in the metabolism of mothers of young children with autism
One of these studies suggests that folic acid and B12 supplements are associated with Autism spectrum disorder (ASD) risk by a u-shaped curve, showing that too little and too much folic acid or B12 supplementation can both lead to an increased risk of ASD [11]
This paper focuses on analyzing the metabolic profile of mothers of young children with ASD and mothers of typically developing children, 2–5 years after birth
Summary
Previous research studies have demonstrated abnormalities in the metabolism of mothers of young children with autism. Previous studies have revealed significant abnormalities in the folate-one carbon metabolism and the transsulfuration pathways of children with ASD [2,3,4,5] and their mothers [6,7,8], resulting in decreased methylation capability, decreased glutathione levels, and increased oxidative stress. The MTHFR gene makes an enzyme, Methylenetetrahydrofolate reductase, which converts 5,10-methylenetetrahydrofolate, a form of folate, to 5methyltetrahydrofolate, a different form of folate. Other studies found that maternal gene variants in the one-carbon metabolism pathway were associated with increased ASD risk when there was no or only low levels of periconceptional prenatal vitamin intake [13, 14]
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