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Folate and methionine metabolism in autism: a systematic review
Penelope A E Main1, Manya T Angley, Philip Thomas
1Sansom Institute, University of South Australia, Adelaide, Australia. penelope.main@postgrads.unisa.edu.au <penelope.main@postgrads.unisa.edu.au>
Insights
Investigating autism and the folate-methionine pathway reveals conflicting evidence. More standardized research is needed to confirm if altered metabolism contributes to autism development.
Area of Science:
- Neuroscience
- Metabolic Disorders
- Genetics
Background:
- Autism spectrum disorder (ASD) is a significant public health concern.
- Emerging evidence suggests potential links between altered folate and methionine metabolism and ASD.
- The folate-methionine cycle is implicated as a potential factor in ASD etiology.
Purpose of the Study:
- To systematically review existing literature on folate-methionine metabolism alterations in autism.
- To examine evidence for the role of these metabolic pathways in the development of autism.
Main Methods:
- A systematic literature review was performed.
- Included studies focused on metabolites, interventions, or genes within the folate-methionine pathway in individuals with autism.
- Eighteen studies met the inclusion criteria, with data on metabolites, interventions, and genetic factors.
Main Results:
- Findings regarding folate-methionine metabolism in autism were inconsistent.
- Heterogeneity among participants, sampling variations, and diverse analytical methods contributed to conflicting results.
- Most genetic studies lacked sufficient power to establish definitive genetic associations.
Conclusions:
- Further research with standardized, adequately powered study designs is necessary.
- Definitive conclusions on the role of the folate-methionine pathway in autism etiology cannot yet be made.
- Investigating the functional benefits of correcting metabolic deficits in autism requires additional study.
Background:
Autism is a complex neurodevelopmental disorder that is increasingly being recognized as a public health issue. Recent evidence has emerged that children with autism may have altered folate or methionine metabolism, which suggests the folate-methionine cycle may play a key role in the etiology of autism.
Objective:
The objective was to conduct a systematic review to examine the evidence for the involvement of alterations in folate-methionine metabolism in the etiology of autism.
Design:
A systematic literature review was conducted of studies reporting data for metabolites, interventions, or genes of the folate-methionine pathway in autism. Eighteen studies met the inclusion criteria, 17 of which provided data on metabolites, 5 on interventions, and 6 on genes and their related polymorphisms.
Results:
The findings of the review were conflicting. The variance in results can be attributed to heterogeneity between subjects with autism, sampling issues, and the wide range of analytic techniques used. Most genetic studies were inadequately powered to provide more than an indication of likely genetic relations.
Conclusions:
The review concluded that further research is required with appropriately standardized and adequately powered study designs before any definitive conclusions can be made about the role for a dysfunctional folate-methionine pathway in the etiology of autism. There is also a need to determine whether functional benefits occur when correcting apparent deficits in folate-methionine metabolism in children with autism.
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