Background:
A diagnosis of autism spectrum disorders (ASD) represents presentations with impairment
in communication and behaviour that vary considerably in their clinical manifestations and etiology as well
as in their likely pathophysiology. A growing body of data indicates that the deleterious effect of oxidative stress,
mitochondrial dysfunction, immune dysregulation and neuroinflammation, as well as their interconnections are
important aspects of the pathophysiology of ASD. Glutathione deficiency decreases the mitochondrial protection
against oxidants and tumor necrosis factor (TNF)-α; immune dysregulation and inflammation inhibit mitochondrial
function through TNF-α; autoantibodies against the folate receptors underpin cerebral folate deficiency,
resulting in disturbed methylation, and mitochondrial dysfunction. Such pathophysiological processes can arise
from environmental and epigenetic factors as well as their combined interactions, such as environmental toxicant
exposures in individuals with (epi)genetically impaired detoxification. The emerging evidence on biochemical
alterations in ASD is forming the basis for treatments aimed to target its biological underpinnings, which is of
some importance, given the uncertain and slow effects of the various educational interventions most commonly
used.
Methods:
Literature-based review of the biomedical treatment options for ASD that are derived from established
pathophysiological processes.
Results:
Most proposed biomedical treatments show significant clinical utility only in ASD subgroups, with
specified pre-treatment biomarkers that are ameliorated by the specified treatment. For example, folinic acid
supplementation has positive effects in ASD patients with identified folate receptor autoantibodies, whilst the
clinical utility of methylcobalamine is apparent in ASD patients with impaired methylation capacity. Mitochondrial
modulating cofactors should be considered when mitochondrial dysfunction is evident, although further
research is required to identify the most appropriate single or combined treatment. Multivitamins/multiminerals
formulas, as well as biotin, seem appropriate following the identification of metabolic abnormalities, with doses
tapered to individual requirements. A promising area, requiring further investigations, is the utilization of antipurinergic
therapies, such as low dose suramin.
Conclusion:
The assessment and identification of relevant physiological alterations and targeted intervention are
more likely to produce positive treatment outcomes. As such, current evidence indicates the utility of an approach
based on personalized and evidence-based medicine, rather than treatment targeted to all that may not always be
beneficial (primum non nocere).
A review of research trends in physiological abnormalities in autism spectrum disorders: immune dysregulation, inflammation, oxidative stress, mitochondrial dysfunction and environmental toxicant exposures
