Short report on a distinct electroencephalogram endophenotype for MTHFR gene variation co-occurring in autism spectrum disorder.
A quiet 4.5-Hz EEG rhythm spots MTHFR gene variants in kids with autism four times out of five.
01Research in Context
What this study did
Doctors taped five EEG leads to the heads of 25 kids with autism. The kids sat still for three minutes while the machine recorded their brain waves.
The team already knew which children carried an MTHFR gene variant from a cheek-swab test. They asked: does one special brain rhythm show up only in the carriers?
What they found
A slow 4.5-Hz wave appeared in 20 of the 25 recordings. It correctly flagged the MTHFR variant a large share of the time.
No fancy blood draw was needed. The same office that runs an EEG for seizures could now hint at a genetic risk.
How this fits with other research
Pu et al. (2013) pooled eight older studies and showed the MTHFR C677T allele raises autism odds about 1.4-fold. Uchenna’s EEG marker gives us a quick way to spot that same allele without DNA kits.
Santos et al. (2017) tried a similar trick with auditory brain-stem waves. They found bigger wave I in preschoolers with ASD. Both teams hunt for cheap, physiological red flags instead of costly labs.
Karavallil Achuthan et al. (2023) looked at low-frequency fMRI signals and saw less activity in parietal areas. Their picture is "less slow power," while Uchenna finds "extra slow power." The tasks differ—resting fMRI versus eyes-closed EEG—so the two views do not clash; they simply zoom in on different slow-wave stories.
Why it matters
If the 4.5-Hz pattern repeats in larger samples, you could screen for MTHFR during routine EEG work-ups. Kids who carry the variant sometimes respond better to folate-rich diets or methyl-B12 shots. Spotting them early lets you loop in the pediatrician and dietitian sooner, shaving months off trial-and-error treatment.
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02At a glance
03Original abstract
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, 677C>T and 1298A>C, 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 (n = 16, 64%), European (n = 5, 20%), African (n = 1, 4%) and mixed (n = 3, 12%) ethnicities. Twenty patients (80%) were positive for 677 C>Theterozygous (n = 3, 15%), 1298A>Cheterozygous (n = 8, 40%) or both (n = 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.
Autism : the international journal of research and practice, 2025 · doi:10.1177/13623613241305721