Short report on a distinct electroencephalogram endophenotype for MTHFR gene variation co-occurring in autism spectrum disorder.

Researchers found a specific brain wave pattern on EEG scans that may help identify a gene variant (MTHFR) in autistic children. They studied 25 children and found this brain wave pattern correctly identified the gene variant 80% of the time. This could potentially lead to a simple, non-invasive test to screen for this genetic variation, which might help guide personalised nutrition treatments.

This preliminary study investigated a specific brain wave pattern (4.5-Hz rhythm) detected on EEG as a potential biomarker for MTHFR gene variants in children with autism. Researchers examined 25 children with autism (ages 2-12) who showed this distinct bilateral parieto-temporal brain wave pattern. Results indicated 80% precision in identifying MTHFR gene variants using this EEG pattern, with 20 of 25 children testing positive for MTHFR variants. The study suggests this non-invasive EEG marker could potentially serve as a screening tool for MTHFR mutations in autistic children, which may inform personalised nutritional interventions targeting folate metabolism.

If validated in larger studies, this EEG biomarker could enable non-invasive screening for MTHFR variants in autistic children, potentially informing personalised folate supplementation and nutritional interventions. However, clinical implementation requires replication in diverse populations and validation studies.

Very small sample size (n=25), single-centre study, lacks control group comparison, preliminary data only, no validation in independent cohort, unclear methodology details, and potential selection bias from clinic-based recruitment.

Anecdotal reports link a distinct, bilateral, parieto-temporally generated 4.5-Hz rhythm on an electroencephalogram to a methylenetetrahydrofolate reductase gene variant co-occurring in autism spectrum disorder, but the validation of its precision is needed. The electroencephalograms of children with autism spectrum disorder showing the distinct bilateral parieto-temporally generated 4.5-Hz rhythm and their clinical chart report on polymerase chain reaction screening for methylenetetrahydrofolate reductase gene variants,and, were retrieved from an outpatient clinic between February 2019 and April 2024. Twenty-five cases were identified. Patients were between 2 and 12 (7 ± 3) years old from Asian ( = 16, 64%), European ( = 5, 20%), African ( = 1, 4%) and mixed ( = 3, 12%) ethnicities.

Twenty patients (80%) were positive for ( = 3, 15%),( = 8, 40%) or both ( = 9, 45%). The polymerase chain reaction testing detected neither variant in 5 (20%) patients. Therefore, the electroencephalogram-endophenotype showed 80% precision in identifying methylenetetrahydrofolate reductase gene variant within the sample. This preliminary data support the precision of the proposed distinct, bilateral, parieto-temporally generated 4.5-Hz rhythm in identifying methylenetetrahydrofolate reductase gene variants and its potential clinical applications as a valuable, non-invasive and objective measure within the population.Lay abstractMethylenetetrahydrofolate reductase mutations refer to genetic variations in the methylenetetrahydrofolate reductase enzyme, which plays an important role in folate metabolism.

Folate is essential for neural development and signalling. Children with autism spectrum disorder have atypical neural signals compared with control. This study used a non-invasive method to identify a distinct neural signal that may be useful in future screening for methylenetetrahydrofolate reductase mutation in children with autism spectrum disorder. Given that the underlying causes of autism spectrum disorder have multiple genetic factors and often require subjective assessment, this study introduces a potential non-invasive screening method for methylenetetrahydrofolate reductase gene mutation.

This method could provide valuable biomarkers for screening and personalised treatments, offering hope for improved risk stratification and bespoke nutritional support and supplements to mitigate the impact on affected individuals and their descendants.