Identification of likely associations between cerebral folate deficiency and complex genetic- and metabolic pathogenesis of autism spectrum disorders by utilization of a pilot interaction modeling approach.
Computer modeling points to folate-linked serine and lysine paths as new lab targets in autism.
01Research in Context
What this study did
Drevon et al. (2017) built a computer model. It looked for links between autism genes and folate pathways.
The model tested how these genes might disturb folate, serine, lysine, and purine metabolism.
What they found
Two gene clusters popped out. One handles serine. The other handles lysine and purine.
Both clusters tie back to folate. The team says these paths are worth testing in kids with ASD.
How this fits with other research
Moretti et al. (2008) first saw autistic traits in kids with cerebral folate deficiency. Daniel’s model now gives a why.
Pu et al. (2013) showed the MTHFR C677T allele raises autism risk. Daniel’s network includes that same gene.
Quadros et al. (2018) found folate receptor autoantibodies cluster in ASD families. Daniel’s paths sit downstream of those antibodies.
Why it matters
You can’t fix genes with ABA, but you can spot kids who might need metabolic labs. If a child has autism plus regression, seizures, or odd movements, ask the pediatrician about folate, MTHFR, or receptor antibody tests. Early folate therapy could protect brain myelin while you keep doing behavior plans.
Want CEUs on This Topic?
The ABA Clubhouse has 60+ free CEUs — live every Wednesday. Ethics, supervision & clinical topics.
Join Free →Add one question to your intake: ‘Any regression, seizures, or odd movements?’ If yes, flag for medical follow-up.
02At a glance
03Original abstract
Recently, cerebral folate deficiency (CFD) was suggested to be involved in the pathogenesis of autism spectrum disorders (ASD). However, the exact role of folate metabolism in the pathogenesis of ASD, identification of underlying pathogenic mechanisms and impaired metabolic pathways remain unexplained. The aim of our study was to develop and test a novel, unbiased, bioinformatics approach in order to identify links between ASD and disturbed cerebral metabolism by focusing on abnormal folate metabolism, which could foster patient stratification and novel therapeutic interventions. An unbiased, automatable, computational workflow interaction model was developed using available data from public databases. The interaction network model of ASD-associated genes with known cerebral expression and function (SFARI) and metabolic networks (MetScape), including connections to known metabolic substrates, metabolites and cofactors involving folates, was established. Intersection of bioinformatically created networks resulted in a limited amount of interaction modules pointing to common disturbed metabolic pathways, linking ASD to CFD. Two independent interaction modules (comprising three pathways) covering enzymes encoded by ASD-related genes and folate cofactors utilizing enzymes were generated. Module 1 suggested possible interference of CFD with serine and lysine metabolism, while module 2 identified correlations with purine metabolism and inosine monophosphate production. Since our approach was primarily conceived as a proof of principle, further amendments of the presented initial model are necessary to obtain additional actionable outcomes. Our modelling strategy identified not only previously known interactions supported by evidence-based analyses, but also novel plausible interactions, which could be validated in subsequent functional and/or clinical studies. Autism Res 2017, 10: 1424-1435. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
Autism research : official journal of the International Society for Autism Research, 2017 · doi:10.1002/aur.1780