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Transmethylation and Oxidative Biomarkers in Children with Autism Spectrum Disorder: A Cross Sectional Study

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Title: Transmethylation and Oxidative Biomarkers in Children with Autism Spectrum Disorder: A Cross Sectional Study
Language: English
Authors: Sheffali Gulati (ORCID 0000-0003-1439-9959), Chinthana L. Narayan, Aakash Mahesan, Gautam Kamila, Seema Kapoor, Pradeep K. Chaturvedi, Vinod Scaria, Thirumurthy Velpandian, Prashant Jauhari, Biswaroop Chakrabarty, Sudip K. R. Datta, R. M. Pandey
Source: Journal of Autism and Developmental Disorders. 2026 56(1):269-277.
Availability: Springer. Available from: Springer Nature. One New York Plaza, Suite 4600, New York, NY 10004. Tel: 800-777-4643; Tel: 212-460-1500; Fax: 212-460-1700; e-mail: customerservice@springernature.com; Web site: https://link.springer.com/
Peer Reviewed: Y
Page Count: 9
Publication Date: 2026
Document Type: Journal Articles
Reports - Research
Descriptors: Autism Spectrum Disorders, Metabolism, Physiology, Children, Severity (of Disability), Perceptual Impairments, Behavior Problems, Correlation, Biochemistry
Assessment and Survey Identifiers: Childhood Autism Rating Scale
DOI: 10.1007/s10803-024-06542-9
ISSN: 0162-3257
1573-3432
Abstract: We aimed to investigate the potential role of biomarkers of transmethylation, oxidative stress, and mitochondrial dysfunction in children with Autism Spectrum Disorder (ASD) by comparing them with that of typically developing children (TDC) controls. We also tried to correlate them with severity of autism, sensory issues, behavioural comorbidities and developmental quotients 119 with ASD and 52 age and sex matched typically developing children (TDC) controls were enrolled excluding those with chronic-illness or on any antioxidant therapy/multivitamins/anti-epileptic drugs. Median levels of biomarkers - serum homocysteine, cysteine, methionine, urine uric acid-to-creatinine ratio, arterial lactate, serum vitamin E, vitamin B12, folate, Nε-carboxymethyllysine, Nω- carboxymethylarginine (CMA), dityrosine and MTHFR C677T polymorphism were calculated. Children with ASD were further characterised using Childhood Autism Rating Scale-2, Childhood behavioural checklist, child sensory profile 2 caregiver questionnaire, Developmental Profile 3 for any correlation with the various biomarker levels. The median level of serum homocysteine in ASD group was 9 μmol/L(Range, 7- 16μmol/L), which was significantly higher than controls 7 μmol/L(Range, 4- 11μmol/L)(p=0.01). The prevalence of hyper-homocystinemia(>15μmol/L) was 13.4% in ASD as compared to 3.8% in controls with a significant difference(p=0.04). Dityrosine level was higher among ASD children when compared to TDC (9.8 vs 2.2 counts per second(cps), p<0.001). No significant correlation was found between prevalence of hyperhomocysteinemia and severity of autism/DQ/behavioural issues. No significant difference was found between the median levels of other biomarkers. Results support possible role of transmethylation defects and oxidative stress in ASD pathogenesis. Further studies are warranted for a better understanding of ASD pathogenesis.
Abstractor: As Provided
Entry Date: 2026
Accession Number: EJ1504714
Database: ERIC
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  Value: &lt;anid&gt;AN0191290301;aut01jan.26;2026Feb04.02:38;v2.2.500&lt;/anid&gt; &lt;title id=&quot;AN0191290301-1&quot;&gt;Transmethylation and Oxidative Biomarkers in Children with Autism Spectrum Disorder: A Cross Sectional Study&#160;&lt;/title&gt; &lt;p&gt;We aimed to investigate the potential role of biomarkers of transmethylation, oxidative stress, and mitochondrial dysfunction in children with Autism Spectrum Disorder (ASD) by comparing them with that of typically developing children (TDC) controls. We also tried to correlate them with severity of autism, sensory issues, behavioural comorbidities and developmental quotients 119 with ASD and 52 age and sex matched typically developing children (TDC) controls were enrolled excluding those with chronic-illness or on any antioxidant therapy/multivitamins/anti-epileptic drugs. Median levels of biomarkers - serum homocysteine, cysteine, methionine, urine uric acid-to-creatinine ratio, arterial lactate, serum vitamin E, vitamin B12, folate, Nε-carboxymethyllysine, Nω- carboxymethylarginine (CMA), dityrosine and MTHFR C677T polymorphism were calculated. Children with ASD were further characterised using Childhood Autism Rating Scale-2, Childhood behavioural checklist, child sensory profile 2 caregiver questionnaire, Developmental Profile 3 for any correlation with the various biomarker levels. The median level of serum homocysteine in ASD group was 9 μmol/L(Range, 7- 16μmol/L), which was significantly higher than controls 7 μmol/L(Range, 4- 11μmol/L)(p=0.01). The prevalence of hyper-homocystinemia(&amp;gt;15μmol/L) was 13.4% in ASD as compared to 3.8% in controls with a significant difference(p=0.04). Dityrosine level was higher among ASD children when compared to TDC (9.8 vs 2.2 counts per second(cps), p&amp;lt;0.001). No significant correlation was found between prevalence of hyperhomocysteinemia and severity of autism/DQ/behavioural issues. No significant difference was found between the median levels of other biomarkers. Results support possible role of transmethylation defects and oxidative stress in ASD pathogenesis. Further studies are warranted for a better understanding of ASD pathogenesis.&lt;/p&gt; &lt;p&gt;Keywords: Biomarkers; Autism spectrum disorder; Transmethylation; Oxidative stress; Medical and Health Sciences Clinical Sciences&lt;/p&gt; &lt;p&gt;Copyright comment Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.&lt;/p&gt; &lt;hd id=&quot;AN0191290301-2&quot;&gt;Introduction&lt;/hd&gt; &lt;p&gt;Autism Spectrum Disorder (ASD) is a heterogenous neurodevelopmental disorder characterised by abnormalities in social relationships with restricted or repetitive behavioural patterns (American Psychiatric Association, [&lt;reflink idref=&quot;bib7&quot; id=&quot;ref1&quot;&gt;7&lt;/reflink&gt;]). The prevalence of ASD has been on the rise accounting for a Disability Adjusted Life Year (DALY) of 38.7% with a worldwide prevalence of 0.6% as compared to 0.4% in Asia (Salari et al., [&lt;reflink idref=&quot;bib43&quot; id=&quot;ref2&quot;&gt;43&lt;/reflink&gt;])(Y.-A. Li et al., [&lt;reflink idref=&quot;bib31&quot; id=&quot;ref3&quot;&gt;31&lt;/reflink&gt;]). As per Centre for Disease Control and Prevention (CDC) estimates 1 in 36 children in USA have ASD and is 3.8 times more prevalent in boys (Maenner et al., [&lt;reflink idref=&quot;bib34&quot; id=&quot;ref4&quot;&gt;34&lt;/reflink&gt;]). The ASD prevalence in India as per the International Clinical Epidemiology Network (INCLEN) study is 1 in 89 children and was the commonest co-occurring disorder among the neurodevelopmental disorder spectrum (Arora et al., [&lt;reflink idref=&quot;bib10&quot; id=&quot;ref5&quot;&gt;10&lt;/reflink&gt;]). ASD is associated with a wide array of comorbidities including sleep disorders, epilepsy, obsessive compulsive disorder, inattention, hyperactivity, anxiety, irritability, phobias, sensory issues, self-harm, toileting problems, immune dysfunction, constipation, abdominal discomfort, selective eating, tantrums and endocrinal problems (Al-Beltagi, [&lt;reflink idref=&quot;bib2&quot; id=&quot;ref6&quot;&gt;2&lt;/reflink&gt;]). Till date, the exact etiopathogenesis behind ASD remains unresolved (Sauer et al., [&lt;reflink idref=&quot;bib46&quot; id=&quot;ref7&quot;&gt;46&lt;/reflink&gt;]). In a broad sense genetic, epigenetic and environmental factors are postulated to be involved in ASD.&lt;/p&gt; &lt;p&gt;Identifying a dependable biomarker to aid in the early diagnosis of ASD could be a transformative factor in addressing the current pandemic of ASD. Various biomarkers have been researched till date and are broadly categorised as genetic, oxidative stress, mitochondrial dysfunction, transmethylation, immune dysregulation, gut dysbiosis, neuropeptide, fatty acids and environmental toxicant biomarkers (Frye et al., [&lt;reflink idref=&quot;bib20&quot; id=&quot;ref8&quot;&gt;20&lt;/reflink&gt;]; Goldani et al., [&lt;reflink idref=&quot;bib22&quot; id=&quot;ref9&quot;&gt;22&lt;/reflink&gt;]; Jensen et al., [&lt;reflink idref=&quot;bib26&quot; id=&quot;ref10&quot;&gt;26&lt;/reflink&gt;]). An integrated multi-omics approach using genomics (DNA), metabalomics (small molecules) and proteomics (proteins) has been shown to be useful in ASD deep profiling. (Ristori et al., [&lt;reflink idref=&quot;bib41&quot; id=&quot;ref11&quot;&gt;41&lt;/reflink&gt;]). Among these, the role of oxidative stress and transmethylation and mitochondrial dysfunction related biomarkers in ASD is focussed here. Superoxide, hydrogen peroxide, peroxyl radicals are few of the examples of reactive oxygen species (ROS) produced by various pathways mediating the oxidative damage (Murphy et al., [&lt;reflink idref=&quot;bib36&quot; id=&quot;ref12&quot;&gt;36&lt;/reflink&gt;]; Sies et al., [&lt;reflink idref=&quot;bib48&quot; id=&quot;ref13&quot;&gt;48&lt;/reflink&gt;]). They are usually negated by antioxidants such as vitamin E and C, glutathione, superoxide dismutase, etc. protecting the vital genetic material from damage(Lobo et al., [&lt;reflink idref=&quot;bib33&quot; id=&quot;ref14&quot;&gt;33&lt;/reflink&gt;]). Factors that could alter this homeostasis, either increase of ROS or decrease of antioxidants, could result in subsequent mitochondrial dysfunction neuroinflammation, epigenetic dysregulation and improper synaptogenesis in a developing brain potentially leading to ASD (Liu et al., [&lt;reflink idref=&quot;bib32&quot; id=&quot;ref15&quot;&gt;32&lt;/reflink&gt;]). Various blood and urine biomarkers of oxidative damage are available. Serum glutathione, folate, vitamin B6, B9, B12, methionine, adenosine, cysteine, transferrin, ceruloplasmin cystathionine, poly-unsaturated fatty acids, advanced glycosylated end products (AGEs), plasma amino acids, isoprostanes, urine catalase activity, uric acid-to-creatine ratio etc. are a few notable ones (Goldani et al., [&lt;reflink idref=&quot;bib22&quot; id=&quot;ref16&quot;&gt;22&lt;/reflink&gt;]; Liu et al., [&lt;reflink idref=&quot;bib32&quot; id=&quot;ref17&quot;&gt;32&lt;/reflink&gt;]). Homocysteine, vitamin B12, folate are involved in DNA methylation, leading to epigenetic changes and ASD (Stanger et al., [&lt;reflink idref=&quot;bib49&quot; id=&quot;ref18&quot;&gt;49&lt;/reflink&gt;]). Studies have indicated increased prevalence of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism (substitution of cysteine to thymine with corresponding amino-acid change alanine to valine) that leads to less thermostable MTHFR enzyme leading to metabolic abnormalities in the folate/homocysteine pathway involved in DNA methylation (Sener et al., [&lt;reflink idref=&quot;bib47&quot; id=&quot;ref19&quot;&gt;47&lt;/reflink&gt;]). Uric acid levels in urine acts as surrogate marker of xanthine oxidase enzyme activity indirectly measuring the oxidative stress (Damodaran &amp;amp; Arumugam, [&lt;reflink idref=&quot;bib15&quot; id=&quot;ref20&quot;&gt;15&lt;/reflink&gt;]). AGEs (Nε-carboxymethyllysine (CML) and Nω-carboxymethylarginine (CMA) are reactive metabolites produced by the non-enzymatic glycosylation of sugars to biological macromolecules such as protein and is increased in oxidative stress along with oxidation adducts like dityrosine (DT) (Anwar et al., [&lt;reflink idref=&quot;bib9&quot; id=&quot;ref21&quot;&gt;9&lt;/reflink&gt;]). As detailed above, there are numerous biomarkers being studied in ASD but many limited by relatively small sample sizes, inconclusive evidences and non-availability of controls. In this study, we aim to investigate the potential roles of various biomarkers in children with ASD by comparing them with typically developing children (TDC). The biomarkers included those of oxidative stress (CML, CMA, DT, vitamin E, methionine, cysteine and urine uric acid/creatinine ratio), transmethylation (MTHFR C677T polymorphism, homocysteine, vitamin B12, folate) and mitochondrial dysfunction (arterial lactate).&lt;/p&gt; &lt;hd id=&quot;AN0191290301-3&quot;&gt;Methods&lt;/hd&gt; &lt;p&gt;A cross‑sectional assessment of metabolic biomarkers in children with ASD was performed and compared with TDC between June 2018 to May 2020. The Institute Ethics Committee had approved the study and it conforms to recognized standards. A written informed consent was taken from caregivers of all children involved in both the groups. Assent was taken wherever applicable.&lt;/p&gt; &lt;hd id=&quot;AN0191290301-4&quot;&gt;Participants&lt;/hd&gt; &lt;p&gt;The study was conducted in a tertiary care centre in Northern India among those children who had attended the general pediatric OPD and Autism specialty clinic. ASD group had children of 2–18 years of age, fulfilling DSM-V criteria for ASD, without any chronic underlying disease and not on any multivitamins or antioxidant supplements for atleast the past 2 months. Children attending general pediatric OPD and immunization services of the hospital with intelligence quotient (IQ) &lt;emph&gt;≥&lt;/emph&gt; 90 without any behavioural concerns, chronic underlying medical conditions and multivitamin antioxidant supplement in the past 2 months were considered as TDC. Children with ASD were further analysed for severity using Childhood Autism Rating Scale (CARS-2), a 15-item rating scale as mild-moderate (score 30 to 36.5) and severe (score &lt;emph&gt;≥&lt;/emph&gt; 37) (Vaughan, [&lt;reflink idref=&quot;bib51&quot; id=&quot;ref22&quot;&gt;51&lt;/reflink&gt;]). The childhood behavioural checklist (CBCL) was used to identify significant behavioural issues (T score &lt;emph&gt;≥&lt;/emph&gt; 65) (Achenbach, [&lt;reflink idref=&quot;bib1&quot; id=&quot;ref23&quot;&gt;1&lt;/reflink&gt;]). Sensory processing ability was assessed using Dunn&#39;s child sensory profile 2 (CSP-2) caregiver questionnaire as typical and non-typical sensory processing by trained personnel (Dunn, [&lt;reflink idref=&quot;bib18&quot; id=&quot;ref24&quot;&gt;18&lt;/reflink&gt;]). Based on Developmental Profile 3 (DP 3) for children aged 2–12 years and Vineland Adaptive Behaviour Scale (VABS) for adolescents aged 13–18 years, they were classified as having average and above (&lt;emph&gt;≥&lt;/emph&gt; 90) or borderline and delayed (&amp;lt; 90) IQ scores (Alpern, [&lt;reflink idref=&quot;bib6&quot; id=&quot;ref25&quot;&gt;6&lt;/reflink&gt;]).&lt;/p&gt; &lt;hd id=&quot;AN0191290301-5&quot;&gt;Sample size&lt;/hd&gt; &lt;p&gt;The sample size was calculated based on study by (James et al., [&lt;reflink idref=&quot;bib25&quot; id=&quot;ref26&quot;&gt;25&lt;/reflink&gt;]) with effect size in plasma homocysteine levels being 0.6 umol/L, 95% confidence interval, 80% power using the formula &lt;emph&gt;n = 2σ&lt;/emph&gt;&lt;sups&gt;2&lt;/sups&gt;(Z&lt;subs&gt;β&lt;/subs&gt;+Z&lt;subs&gt;α/2&lt;/subs&gt;)/Effect Size&lt;sups&gt;2&lt;/sups&gt;] [Zβ = Representative (Z statistic) of the desired power, Zα/2 = Representative (Z statistic) of desired level of statistical significance], which turned out to be100 children with ASD. The controls were enrolled in an age (2–5 years, 6–10 years, 11–18 years) and gender (males, females) matched ratio of ASD: TDC being 2:1.&lt;/p&gt; &lt;hd id=&quot;AN0191290301-6&quot;&gt;Procedure&lt;/hd&gt; &lt;p&gt;The children fulfilling inclusion criteria were enrolled and underwent evaluation by a child psychologist for administering CARS-2, DP-3/VABS, CSP 2 and CBCL. After the 100 children with ASD were enrolled, age and sex matched TDC were screened and evaluated by the child psychologist using DP-3 and CBCL. Fifty such TDC fulfilling the inclusion criteria were enrolled in the study. Ethylenediaminetetra-acetic acid (EDTA) tubes were used for blood collection from the participants of both the groups (ASD and TDC), which was collected early in the morning with minimum 4 h of fasting. Immediate centrifugation of the blood sample at 2000 rpm for 10 min separated the plasma from the cells, which was stored at − 80 &#176;C and transferred to respective labs on dry ice maintaining the cold chain. EDTA samples for sanger sequencing of the MTHFR gene for C667T polymorphism were kept separately. Atleast 2 ml of midstream morning urine sample was also collected in a sterile plain vial. Arterial lactate was assessed immediately using an automated blood gas analyser.&lt;/p&gt; &lt;hd id=&quot;AN0191290301-7&quot;&gt;Assay of Biomarkers&lt;/hd&gt; &lt;p&gt;The MTHFR C677T polymorphism analysis was done using Sanger sequencing. The normal variants were labelled CC and CT, while TT variants were the thermolabile variants, with polymorphism in position 677 of MTHFR gene resulting in substitution of alanine to valine. Folic acid, vitamin B12, vitamin E, homocysteine, methionine and cysteine levels were analysed using high performance liquid chromatography (HPLC). AGEs (CMA, CML) and oxidation adduct DT levels were also analysed using liquid chromatography and mass spectrometry. Multiple reaction monitoring mode was used. Absolute quantification was performed for CML and relative quantification was used for CMA and DT. The MTHFR C677T polymorphism analysis was done using Sanger sequencing. The normal variants were labelled CC and CT, while TT variants were the thermolabile variants, with polymorphism in position 677 of MTHFR gene resulting in substitution of alanine to valine. Urine uric acid/creatinine ratio was calculated using spectrophotometry. The details of AGEs and MTHFR analysis are provided in Supplementary File 1.&lt;/p&gt; &lt;hd id=&quot;AN0191290301-8&quot;&gt;Statistical Analysis&lt;/hd&gt; &lt;p&gt;Data was entered in MS excel spread sheet and statistical analysis was done using Stata 14.2 (Stata Corp, College Station, TX). Kolmogorov–Smirnov test was used to check normality of the data distribution. Significance was evaluated by Student&#39;s t test for parametrical and by Mann–Whitney U test for nonparametrically distributed data. For analysis of multiple analytes without pre-conceived hypothesis, Bonferroni correction was made. Odds ratio (OR) and 95% confidence intervals (CI) were calculated to analyse the strength of correlation of MTHFR (C677T) polymorphism with the risk of ASD. Chi-Square test was used to test the Hardy-Weinberg principle in both the groups. Chi-Square test was used to test the Hardy-Weinberg principle in both the groups.&lt;/p&gt; &lt;hd id=&quot;AN0191290301-9&quot;&gt;Community Involvement&lt;/hd&gt; &lt;p&gt;There was no community involvement in the reported study.&lt;/p&gt; &lt;hd id=&quot;AN0191290301-10&quot;&gt;Results&lt;/hd&gt; &lt;p&gt;A total of 162 children with ASD and 72 TDC were screened during the study period, out of which 119 children with ASD and 52 TDC were enrolled. The study flow is depicted in Fig. 1. The ASD group was age stratified into 3 groups 2–5 years, 6–10 years and 11–18 years. The TDC group was matched with stratified age group and sex of ASD participants.&lt;/p&gt; &lt;p&gt;Graph: Fig. 1 Participant flow chart&lt;/p&gt; &lt;p&gt;The mean age (SD) of the children was 7.3 (&#177; 3.2) years and 6.9 (&lt;emph&gt;&#177;&lt;/emph&gt; 3.3) years, in the ASD and TDC groups respectively. The mean IQ in ASD group was significantly lower than the TDC group (64.2 vs. 98) (p- &amp;lt;0.001). The male: female ratio for ASD group was 4.4:1 which was comparable to 4.7:1 in the control group. Severe autism was noted in 54.6%, sensory issues in 75.6%, behaviour issues in 84.9% and below average intelligence in 77.3% ASD children. The baseline demographic details are outlined in Table 1.&lt;/p&gt; &lt;p&gt;Table 1 Baseline demographic details of ASD and TDC groups&lt;/p&gt; &lt;p&gt; &lt;ephtml&gt; &amp;lt;table rules=&quot;groups&quot;&amp;gt;&amp;lt;thead&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;th align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;Characteristic&amp;lt;/p&amp;gt;&amp;lt;/th&amp;gt;&amp;lt;th align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;ASD (&amp;lt;italic&amp;gt;n&amp;lt;/italic&amp;gt; = 119)&amp;lt;/p&amp;gt;&amp;lt;/th&amp;gt;&amp;lt;th align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;Controls (&amp;lt;italic&amp;gt;n&amp;lt;/italic&amp;gt; = 52)&amp;lt;/p&amp;gt;&amp;lt;/th&amp;gt;&amp;lt;th align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;italic&amp;gt;p&amp;lt;/italic&amp;gt;-value&amp;lt;/p&amp;gt;&amp;lt;/th&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;/thead&amp;gt;&amp;lt;tbody&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;bold&amp;gt;Mean age&amp;lt;/bold&amp;gt; (Years, &amp;lt;italic&amp;gt;&amp;amp;#177;&amp;lt;/italic&amp;gt; SD)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td char=&quot;&amp;amp;#177;&quot; align=&quot;char&quot;&amp;gt;&amp;lt;p&amp;gt;7.3 &amp;lt;italic&amp;gt;&amp;amp;#177;&amp;lt;/italic&amp;gt; 3.2&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td char=&quot;&amp;amp;#177;&quot; align=&quot;char&quot;&amp;gt;&amp;lt;p&amp;gt;6.9 &amp;lt;italic&amp;gt;&amp;amp;#177;&amp;lt;/italic&amp;gt; 3.3&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;0.7&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;bold&amp;gt;Age subgroup&amp;lt;/bold&amp;gt;&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;2 &amp;lt;italic&amp;gt;&amp;amp;#8804;&amp;lt;/italic&amp;gt; 5 years&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;6 &amp;lt;italic&amp;gt;&amp;amp;#8804;&amp;lt;/italic&amp;gt; 10 years&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;11 &amp;lt;italic&amp;gt;&amp;amp;#8804;&amp;lt;/italic&amp;gt; 18 years&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;36 (30.2%)&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;66 (55.4%)&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;17 (14.2%)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;16 (30.7%)&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;28 (53.8%)&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;8 (15.3%)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;0.94&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;bold&amp;gt;Sex&amp;lt;/bold&amp;gt;&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;Male&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;Female&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;Male: Female&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;97 (81.5%)&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;22 (18.5%)&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;4.4:1&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;43 (82.6%)&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;9 (17.4%)&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;4.7:1&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;0.92&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;bold&amp;gt;Intelligence quotient&amp;lt;/bold&amp;gt;&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td char=&quot;&amp;amp;#177;&quot; align=&quot;char&quot;&amp;gt;&amp;lt;p&amp;gt;64.2 &amp;lt;italic&amp;gt;&amp;amp;#177;&amp;lt;/italic&amp;gt; 7.2&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td char=&quot;&amp;amp;#177;&quot; align=&quot;char&quot;&amp;gt;&amp;lt;p&amp;gt;98 &amp;lt;italic&amp;gt;&amp;amp;#177;&amp;lt;/italic&amp;gt; 8.8&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;amp;#60; 0.001&amp;amp;#42;&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;bold&amp;gt;Severity of Autism&amp;lt;/bold&amp;gt;&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;Mild to moderate&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;Severe Autism&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;54 (45.4%)&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;65 (54.6%)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;-&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;-&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;bold&amp;gt;Intelligence quotient&amp;lt;/bold&amp;gt;&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;Average &amp;amp; above average&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;Borderline &amp;amp; delayed&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;27 (22.7%)&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;92 (77.3%)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;-&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;-&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;bold&amp;gt;Sensory profile 2&amp;lt;/bold&amp;gt;&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;No sensory issues&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;Sensory issues present&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;29 (22.4%)&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;90 (75.6%)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;-&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;-&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;bold&amp;gt;Behavioural issues CBCL T score&amp;lt;/bold&amp;gt;&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;Normal range&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;Borderline &amp;amp; Clinical range&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;18 (15.1%)&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;101(84.9%)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;-&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;-&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;/tbody&amp;gt;&amp;lt;/table&amp;gt; &lt;/ephtml&gt; &lt;/p&gt; &lt;p&gt;In view of non-availability of additional PCR probes, only the first 100 of ASD and 50 of TDC groups blood samples were evaluated for MTHFR C677T polymorphism. The frequencies of CC, CT and TT genotypes in ASD group were 84%, 14% and 2% respectively and in TDC group were 86%, 12% and 2% respectively which was not statistically significant. (Fig. 2) The genotype frequencies were in concordance with the Hardy-Weinberg equilibrium in both the ASD and TDC groups. (Table 2) All the 119 samples of children with ASD and 52 samples of TDC were processed for the other biomarkers of transmethylation and oxidative stress. The median level (range) of serum homocysteine in ASD group was 9 (7–16) &#181;mol/L compared to a significantly lower level of 7 (4–11) &#181;mol/L in the TDC group (&lt;emph&gt;p&lt;/emph&gt; = 0.01). The proportion of children who had hyperhomocysteinemia (&amp;gt; 15 &#181;mol/L) was significantly higher in ASD group compared to TDC (13.4% vs. 3.8%; &lt;emph&gt;p&lt;/emph&gt; = 0.04). The level of severity of autism, developmental/intelligence quotient, presence of sensory and behavioural issues did not show any correlation with hyperhomocysteinemia (Table 3). No statistically significant difference was observed in the median levels of plasma cysteine, methionine, vitamin B12 and folate between the two groups. The prevalence of vitamin B12 deficiency (&amp;lt; 25 pmol/L) (15.9% vs. 15.3%, &lt;emph&gt;p&lt;/emph&gt; = 0.57) and folate deficiency (&amp;lt; 3.5 ng/ml) (11.7% vs. 9.6%, &lt;emph&gt;p&lt;/emph&gt; = 0.55) was similar in both the groups. Among the oxidative biomarkers, DT levels was significantly higher among ASD children when compared to TDC (9.8 vs. 2.2 counts per second (cps); &lt;emph&gt;p&lt;/emph&gt; &amp;lt; 0.001). CMA, CML, serum vitamin E levels, urine uric acid/creatinine ratio and arterial blood lactate levels were similar in both the groups. The findings are summarised in Table 4.&lt;/p&gt; &lt;p&gt;Graph: Fig. 2 Bar diagram showing distribution of CC, CT, TT genotypes in both ASD and TDC groups&lt;/p&gt; &lt;p&gt;Table 2 Genotype and allelic frequencies of MTHFR C677T gene polymorphisms in ASD and TDC groups along with Hardy Weinberg Equilibrium testing&lt;/p&gt; &lt;p&gt; &lt;ephtml&gt; &amp;lt;table rules=&quot;groups&quot;&amp;gt;&amp;lt;thead&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;th align=&quot;left&quot; /&amp;gt;&amp;lt;th align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;ASD (&amp;lt;italic&amp;gt;n&amp;lt;/italic&amp;gt; = 100)&amp;lt;/p&amp;gt;&amp;lt;/th&amp;gt;&amp;lt;th align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;TDC (&amp;lt;italic&amp;gt;n&amp;lt;/italic&amp;gt; = 50)&amp;lt;/p&amp;gt;&amp;lt;/th&amp;gt;&amp;lt;th align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;Odds ratio (95% CI)&amp;lt;/p&amp;gt;&amp;lt;/th&amp;gt;&amp;lt;th align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;italic&amp;gt;P&amp;lt;/italic&amp;gt; value&amp;lt;/p&amp;gt;&amp;lt;/th&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;/thead&amp;gt;&amp;lt;tbody&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot; colspan=&quot;5&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;bold&amp;gt;Genotype frequency&amp;lt;/bold&amp;gt;&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;bold&amp;gt;CC&amp;lt;/bold&amp;gt;&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;84 (84%)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;43 (86%)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;0.85 (0.32-2.23)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;0.75&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;bold&amp;gt;CT&amp;lt;/bold&amp;gt;&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;14 (14%)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;6 (12%)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;1.19 (0.48-3.00)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;0.73&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;bold&amp;gt;TT&amp;lt;/bold&amp;gt;&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;2(2%)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;1(2%)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;1.02 (0.07&amp;amp;#8211;14.40)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;1.00&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot; colspan=&quot;5&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;bold&amp;gt;Allele frequency&amp;lt;/bold&amp;gt;&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;bold&amp;gt;C&amp;lt;/bold&amp;gt;&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;182 (91%)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;92 (92%)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;0.88 (0.37-2.10)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;0.77&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;bold&amp;gt;T&amp;lt;/bold&amp;gt;&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;18 (9%)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;8 (8%)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;1.13(0.37&amp;amp;#8211;3.54)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;0.50&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot; colspan=&quot;5&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;bold&amp;gt;MTHFR C677T Genotype frequency&amp;lt;/bold&amp;gt;&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;bold&amp;gt;Genotype&amp;lt;/bold&amp;gt;&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot; colspan=&quot;2&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;bold&amp;gt;Observed frequency&amp;lt;/bold&amp;gt;&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot; colspan=&quot;2&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;bold&amp;gt;Hardy weinberg equilibrium&amp;lt;/bold&amp;gt;&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;&amp;lt;bold&amp;gt;Expected frequency&amp;lt;/bold&amp;gt;&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot; colspan=&quot;5&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;bold&amp;gt;ASD&amp;lt;/bold&amp;gt;&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;bold&amp;gt;CC&amp;lt;/bold&amp;gt;&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot; colspan=&quot;2&quot;&amp;gt;&amp;lt;p&amp;gt;84&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot; colspan=&quot;2&quot;&amp;gt;&amp;lt;p&amp;gt;82.81&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;bold&amp;gt;CT&amp;lt;/bold&amp;gt;&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot; colspan=&quot;2&quot;&amp;gt;&amp;lt;p&amp;gt;14&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot; colspan=&quot;2&quot;&amp;gt;&amp;lt;p&amp;gt;16.38&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;bold&amp;gt;TT&amp;lt;/bold&amp;gt;&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot; colspan=&quot;2&quot;&amp;gt;&amp;lt;p&amp;gt;2&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot; colspan=&quot;2&quot;&amp;gt;&amp;lt;p&amp;gt;0.81&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot; colspan=&quot;5&quot;&amp;gt;&amp;lt;p&amp;gt;X&amp;lt;sup&amp;gt;2&amp;lt;/sup&amp;gt; = 2.10&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot; colspan=&quot;5&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;bold&amp;gt;TDC&amp;lt;/bold&amp;gt;&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;bold&amp;gt;CC&amp;lt;/bold&amp;gt;&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot; colspan=&quot;2&quot;&amp;gt;&amp;lt;p&amp;gt;43&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot; colspan=&quot;2&quot;&amp;gt;&amp;lt;p&amp;gt;42.32&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;bold&amp;gt;CT&amp;lt;/bold&amp;gt;&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot; colspan=&quot;2&quot;&amp;gt;&amp;lt;p&amp;gt;6&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot; colspan=&quot;2&quot;&amp;gt;&amp;lt;p&amp;gt;7.36&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;bold&amp;gt;TT&amp;lt;/bold&amp;gt;&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot; colspan=&quot;2&quot;&amp;gt;&amp;lt;p&amp;gt;1&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot; colspan=&quot;2&quot;&amp;gt;&amp;lt;p&amp;gt;0.32&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot; colspan=&quot;5&quot;&amp;gt;&amp;lt;p&amp;gt;X&amp;lt;sup&amp;gt;2&amp;lt;/sup&amp;gt; = 1.70&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;/tbody&amp;gt;&amp;lt;/table&amp;gt; &lt;/ephtml&gt; &lt;/p&gt; &lt;p&gt;Table 3 Correlation between hyperhomocyteinemia and severity levels of ASD, IQ scores, sensory and behavioural issues&lt;/p&gt; &lt;p&gt; &lt;ephtml&gt; &amp;lt;table rules=&quot;groups&quot;&amp;gt;&amp;lt;thead&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;th align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;Parameters&amp;lt;/p&amp;gt;&amp;lt;/th&amp;gt;&amp;lt;th align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;Hyperhomocysteinemia [&amp;lt;italic&amp;gt;n&amp;lt;/italic&amp;gt; (%)]&amp;lt;/p&amp;gt;&amp;lt;/th&amp;gt;&amp;lt;th align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;italic&amp;gt;P&amp;lt;/italic&amp;gt;-value&amp;lt;/p&amp;gt;&amp;lt;/th&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;/thead&amp;gt;&amp;lt;tbody&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot; colspan=&quot;3&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;bold&amp;gt;Severity of ASD (CARS-2)&amp;lt;/bold&amp;gt;&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;Mild to moderate Autism (&amp;lt;italic&amp;gt;n&amp;lt;/italic&amp;gt; = 54)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;7 (13%)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot; rowspan=&quot;2&quot;&amp;gt;&amp;lt;p&amp;gt;0.90&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;Severe Autism (&amp;lt;italic&amp;gt;n&amp;lt;/italic&amp;gt; = 65)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;9 (13.8%)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot; colspan=&quot;3&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;bold&amp;gt;IQ scores (DP-3/VABS)&amp;lt;/bold&amp;gt;&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;Average and above (&amp;lt;italic&amp;gt;&amp;amp;#8805;&amp;lt;/italic&amp;gt; 90) (&amp;lt;italic&amp;gt;n&amp;lt;/italic&amp;gt; = 27)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;4 (14.8%)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot; rowspan=&quot;2&quot;&amp;gt;&amp;lt;p&amp;gt;0.13&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;Boderline and below(&amp;amp;#60; 90) (&amp;lt;italic&amp;gt;n&amp;lt;/italic&amp;gt; = 92)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;12(13%)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot; colspan=&quot;3&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;bold&amp;gt;Sensory issues (CSP-2)&amp;lt;/bold&amp;gt;&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;Absent (&amp;lt;italic&amp;gt;n&amp;lt;/italic&amp;gt; = 29)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;5(17.2%)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot; rowspan=&quot;2&quot;&amp;gt;&amp;lt;p&amp;gt;0.45&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;Present (&amp;lt;italic&amp;gt;n&amp;lt;/italic&amp;gt; = 90)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;11(12.2%)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot; colspan=&quot;3&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;bold&amp;gt;Behavioural issues (CBCL)&amp;lt;/bold&amp;gt;&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;Absent (&amp;lt;italic&amp;gt;n&amp;lt;/italic&amp;gt; = 18)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;2(11.1%)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot; rowspan=&quot;2&quot;&amp;gt;&amp;lt;p&amp;gt;0.60&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;Present (&amp;lt;italic&amp;gt;n&amp;lt;/italic&amp;gt; = 101)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;10(9.9%)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;/tbody&amp;gt;&amp;lt;/table&amp;gt; &lt;/ephtml&gt; &lt;/p&gt; &lt;p&gt;Table 4 Comparison of transmethylation and oxidative biomarkers between ASD and TDC groups&lt;/p&gt; &lt;p&gt; &lt;ephtml&gt; &amp;lt;table rules=&quot;groups&quot;&amp;gt;&amp;lt;thead&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;th align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;Variable&amp;lt;/p&amp;gt;&amp;lt;/th&amp;gt;&amp;lt;th align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;ASD Cases (&amp;lt;italic&amp;gt;n&amp;lt;/italic&amp;gt; = 119)&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;Median (Range)&amp;lt;/p&amp;gt;&amp;lt;/th&amp;gt;&amp;lt;th align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;Control (&amp;lt;italic&amp;gt;n&amp;lt;/italic&amp;gt; = 52)&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;Median (Range)&amp;lt;/p&amp;gt;&amp;lt;/th&amp;gt;&amp;lt;th align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;lt;italic&amp;gt;P&amp;lt;/italic&amp;gt; value&amp;lt;/p&amp;gt;&amp;lt;/th&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;/thead&amp;gt;&amp;lt;tbody&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;Serum Homocysteine (&amp;amp;#181;mol/L)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;9 (7&amp;amp;#8211;16)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;7 (4&amp;amp;#8211;11)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;0.01&amp;amp;#42;&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;Plasma Cysteine (&amp;amp;#181;mol/L)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;343.3 (216&amp;amp;#8211;685)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;366.5 (243&amp;amp;#8211;698)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;0.43&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;Plasma Methionine (&amp;amp;#181;mol/L)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;26.4 (19&amp;amp;#8211;34)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;27.6 (20&amp;amp;#8211;38)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;0.56&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;Vitamin B 12 (pmol/L)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;95 (49&amp;amp;#8211;130)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;95 (68&amp;amp;#8211;182)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;0.82&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;Folate l (ng/ml)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;8 (6&amp;amp;#8211;10)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;8 (7&amp;amp;#8211;13)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;0.10&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;Urine uric acid/ creatinine ratio&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;0.49 (0.38-56)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;0.42 (0.34-54)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;0.57&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;N&amp;amp;#949;-Carboxymethyl lysine (ng/ml)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;7.4 (6.1&amp;amp;#8211;9.8)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;7.6 (6.2&amp;amp;#8211;10.0)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;0.89&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;N&amp;amp;#969;-Carboxymethyl arginine(cps)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;14.9 (8.6&amp;amp;#8211;26.6)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;12.8(7.6&amp;amp;#8211;24.8)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;0.56&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;Dityrosine (cps)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;9.8 (2.1&amp;amp;#8211;18.8)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;2.2 (1.5&amp;amp;#8211;4.9)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;&amp;amp;#60; 0.001&amp;amp;#42;&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;Arterial lactate (mmol/L)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;0.5 (0.4&amp;amp;#8211;0.6)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;0.5(0.4&amp;amp;#8211;0.6)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;0.74&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;tr&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;Serum Vitamin E (&amp;amp;#181;g/ml)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;10.6 (6.8&amp;amp;#8211;14.5)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;11.6 (7.3&amp;amp;#8211;16.2)&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;td align=&quot;left&quot;&amp;gt;&amp;lt;p&amp;gt;0.38&amp;lt;/p&amp;gt;&amp;lt;/td&amp;gt;&amp;lt;/tr&amp;gt;&amp;lt;/tbody&amp;gt;&amp;lt;/table&amp;gt; &lt;/ephtml&gt; &lt;/p&gt; &lt;p&gt;*significant p value, cps- counts per second, &#181;g/ml- microgram/millilitre, &#181;mol/L- micromoles/litre, mmol/L- millimoles/litre, ng/ml- nanogram/millilitre, pmol/l- picomoles per litre,&lt;/p&gt; &lt;hd id=&quot;AN0191290301-11&quot;&gt;Discussion&lt;/hd&gt; &lt;p&gt;The current cross sectional study compares the levels of some of the transmethylation and oxidative biomarkers between ASD and TDC groups. MTHFR C677T single nucleotide polymorphism reduces the thermostability of the MTHFR enzyme at higher temperatures, leading to alteration of DNA methylation and gene expression (Sener et al., [&lt;reflink idref=&quot;bib47&quot; id=&quot;ref27&quot;&gt;47&lt;/reflink&gt;]). The T allele frequency has been evaluated worldwide. The Japanese, Chinese, Caucasians, Hispanics showed relatively high T allele frequency of 35–45% with Mexican population having the highest frequency of 59% (Mutchinick et al., [&lt;reflink idref=&quot;bib37&quot; id=&quot;ref28&quot;&gt;37&lt;/reflink&gt;]; Guo et al., [&lt;reflink idref=&quot;bib23&quot; id=&quot;ref29&quot;&gt;23&lt;/reflink&gt;]; Yadav et al., [&lt;reflink idref=&quot;bib52&quot; id=&quot;ref30&quot;&gt;52&lt;/reflink&gt;]). The Indian, African and Indonesian population have a lower T allele frequency ranging from 6 to 14% (Chillemi et al., [&lt;reflink idref=&quot;bib14&quot; id=&quot;ref31&quot;&gt;14&lt;/reflink&gt;]; Sadewa et al., [&lt;reflink idref=&quot;bib42&quot; id=&quot;ref32&quot;&gt;42&lt;/reflink&gt;]). The studies from the Indian subcontinent show a frequency ranging from 8 to 16% which is similar to our study (ASD − 9% and controls − 8%) (Saraswathy et al., [&lt;reflink idref=&quot;bib45&quot; id=&quot;ref33&quot;&gt;45&lt;/reflink&gt;]; Yadav et al., [&lt;reflink idref=&quot;bib52&quot; id=&quot;ref34&quot;&gt;52&lt;/reflink&gt;]). A meta-analysis on MTHFR C677T polymorphism and ASD reported a significant association of homozygous TT genotype with ASD when compared to CC genotype with an odds ratio of 2.26 (C.I.- 1.3–3.9). The heterozygous CT genotype too had significantly higher odds ratio of 1.57 (C.I.- 1.14–2.16) compared to CC genotype (Frustaci et al., [&lt;reflink idref=&quot;bib19&quot; id=&quot;ref35&quot;&gt;19&lt;/reflink&gt;]). However, our data did not support this hypothesis and did not demonstrate a possible risk association of MTHFR C677T polymorphism with ASD, which is consistent with few other studies (Paşca et al., [&lt;reflink idref=&quot;bib40&quot; id=&quot;ref36&quot;&gt;40&lt;/reflink&gt;]; Santos et al., [&lt;reflink idref=&quot;bib44&quot; id=&quot;ref37&quot;&gt;44&lt;/reflink&gt;]; Sener et al., [&lt;reflink idref=&quot;bib47&quot; id=&quot;ref38&quot;&gt;47&lt;/reflink&gt;]).&lt;/p&gt; &lt;p&gt;A defect in methionine cycle affects S-adenosyl methionine production which is needed for normal methylation activity as well as antioxidant activity mediated via cysteine and glutathione, potentially leading to various neuropsychiatric disorders (Gao et al., [&lt;reflink idref=&quot;bib21&quot; id=&quot;ref39&quot;&gt;21&lt;/reflink&gt;]). Hence, we evaluated the defect in transmethylation pathway by analysing the homocysteine, methionine, cysteine, folate and vitamin B12 levels. The median serum homocysteine levels were significantly high among the autistic children when compared to the age and gender matched healthy controls, which was in accordance with the previous studies (Ali et al., [&lt;reflink idref=&quot;bib5&quot; id=&quot;ref40&quot;&gt;5&lt;/reflink&gt;]; B. Li et al., [&lt;reflink idref=&quot;bib31&quot; id=&quot;ref41&quot;&gt;31&lt;/reflink&gt;]; Kałużna-Czaplińska et al., [&lt;reflink idref=&quot;bib27&quot; id=&quot;ref42&quot;&gt;27&lt;/reflink&gt;]). An updated metanalysis of 31 studies also showed significantly increased peripheral blood levels of homocysteine in children with ASD (B.-Q. Guo et al., [&lt;reflink idref=&quot;bib24&quot; id=&quot;ref43&quot;&gt;24&lt;/reflink&gt;]). Elevated serum levels of homocysteine can be due to various causes including both genetic (like MTHFR C677T polymorphism) and nutritional (like deficient folate and vitamin B12 levels) (Al-Farsi et al., [&lt;reflink idref=&quot;bib3&quot; id=&quot;ref44&quot;&gt;3&lt;/reflink&gt;]); Kumar et al., [&lt;reflink idref=&quot;bib29&quot; id=&quot;ref45&quot;&gt;29&lt;/reflink&gt;]). Our study did not show any difference in MTHFR C677T polymorphism, median levels of folate and vitamin B12 between the two groups indicating homocysteine as a potentially independent biomarker for ASD. Although there have been conflicting results, a recent meta-analysis of 87 studies showed reduced methionine and cysteine levels in children with ASD (Chen et al., [&lt;reflink idref=&quot;bib13&quot; id=&quot;ref46&quot;&gt;13&lt;/reflink&gt;]). Our study did not show significant difference in median methionine, cysteine, vitamin B12 or folate levels similar to a study done among 64 ASD cases (Vargason et al., [&lt;reflink idref=&quot;bib50&quot; id=&quot;ref47&quot;&gt;50&lt;/reflink&gt;]).&lt;/p&gt; &lt;p&gt;The oxidative stress biomarkers assessed in the study were AGEs like CMA &amp;amp; CML and protein oxidation adducts like DT, urine uric acid/creatinine ratio, vitamin E and arterial blood lactate. A study conducted on 38 children with ASD showed increased levels of CML, CMA and DT in plasma compared to TDC (Anwar et al., [&lt;reflink idref=&quot;bib9&quot; id=&quot;ref48&quot;&gt;9&lt;/reflink&gt;]). Another study in 139 children with ASD showed urinary 8-Hydroxy-2′-Deoxyguanosine and DT levels to be good predictors of ASD (Osredkar, [&lt;reflink idref=&quot;bib39&quot; id=&quot;ref49&quot;&gt;39&lt;/reflink&gt;]). In our study, only DT level was significantly higher in ASD compared to TDC, even after Bonferroni correction. Both ROS and dual oxygenase regulatory pathway (DUOX) lead to formation of tyrosine protein oxidation adducts. DUOX activity plays an important role in gut mucosal immunity and homeostasis with the gut microbiota, thus hinting a role of gut microbiota in the development of ASD (Bae et al., [&lt;reflink idref=&quot;bib11&quot; id=&quot;ref50&quot;&gt;11&lt;/reflink&gt;]; Chang et al., [&lt;reflink idref=&quot;bib12&quot; id=&quot;ref51&quot;&gt;12&lt;/reflink&gt;]). Uric acid, an end product of purine metabolism, marker of xanthine oxidase activity which promotes superoxide production, was found to be increased in the urine of children with ASD (Damodaran &amp;amp; Arumugam, [&lt;reflink idref=&quot;bib15&quot; id=&quot;ref52&quot;&gt;15&lt;/reflink&gt;]). However, our study did not reveal any significant difference in the urine uric acid/creatinine ratio between both the groups. Vitamin E, a natural antioxidant has been shown to be low in few studies in children with ASD (Al-Gadani et al., [&lt;reflink idref=&quot;bib4&quot; id=&quot;ref53&quot;&gt;4&lt;/reflink&gt;]; Krajcovicova-Kudlackova et al., [&lt;reflink idref=&quot;bib28&quot; id=&quot;ref54&quot;&gt;28&lt;/reflink&gt;]). Our study did not support the findings of these previous studies with both the groups showing similar levels of vitamin E.&lt;/p&gt; &lt;p&gt;Elevated arterial lactate as a marker of mitochondrial dysfunction which could potentially lead to ASD has been noted in few studies (Dhillon et al., [&lt;reflink idref=&quot;bib17&quot; id=&quot;ref55&quot;&gt;17&lt;/reflink&gt;]; Oh et al., [&lt;reflink idref=&quot;bib38&quot; id=&quot;ref56&quot;&gt;38&lt;/reflink&gt;]). But, the same could not be replicated in our study.&lt;/p&gt; &lt;p&gt;A meta-analysis of 33 RCTs has shown early intervention in ASD showed positive outcomes for cognitive ability, daily living skills, and motor skills (Daniolou et al., [&lt;reflink idref=&quot;bib16&quot; id=&quot;ref57&quot;&gt;16&lt;/reflink&gt;]). Another meta-analysis of 13 double blinded RCTs showed a positive role of antioxidants like N-Acetyl cysteine compared to placebo in improving irritability, communication and stereotypic behaviour in children with ASD. These studies altogether signify the role of biomarkers discussed above in our study having potential role in earlier diagnosis and better treatment of ASD going forward. Our study had certain limitations, like inability to analyse the association between presence of comorbidities and the biomarker levels, and the causality could not be ascertained due to cross-sectional nature of the study. VABS, an adaptive scale, measures an individual&#39;s adaptive functioning, with scores that often closely correlate with IQ. However, recent findings suggest that with advancing age, the correlation between IQ and adaptive functioning scores may diminish (McQuaid et al., [&lt;reflink idref=&quot;bib35&quot; id=&quot;ref58&quot;&gt;35&lt;/reflink&gt;]). Consequently, VABS may not be a precise surrogate for IQ. In our study, VABS was used for adolescents aged 13–18 years, where the DP-3 was not applicable, while DP-3 was employed for the other age groups. Strengths of the study were that the study population was heterogeneous, and the parameters were analysed in a good sample size of children with ASD, which was compared with age and sex matched TDC. We were also able to analyse multiple oxidative stress and transmethylation pathway biomarkers.&lt;/p&gt; &lt;hd id=&quot;AN0191290301-12&quot;&gt;Conclusion&lt;/hd&gt; &lt;p&gt;Our study showed increased homocysteine and DT levels in ASD group compared to TDC. Hyperhomocysteinemia was independent of MTHFR C677T gene polymorphism, vitamin B12 and folate levels suggesting hyperhomocysteinemia as an independent biomarker. Increased DT may indicate gut microbiota dysfunction mediated by increased DUOX activity. CMA, CML, vitamin E, methionine, cysteine and arterial lactate levels were normal. Results support the plausible role of oxidative stress and transmethylation defects in ASD pathogenesis. Such biomarkers may hold the key for developing earlier diagnostic algorithms and support future studies in the role of antioxidants in treatment of ASD.&lt;/p&gt; &lt;hd id=&quot;AN0191290301-13&quot;&gt;Acknowledgements&lt;/hd&gt; &lt;p&gt;None.&lt;/p&gt; &lt;hd id=&quot;AN0191290301-14&quot;&gt;Data Availability&lt;/hd&gt; &lt;p&gt;The data that support the findings of this study are available on request from the corresponding author [SG].&lt;/p&gt; &lt;hd id=&quot;AN0191290301-15&quot;&gt;Declarations&lt;/hd&gt; &lt;p&gt;&lt;/p&gt; &lt;hd id=&quot;AN0191290301-16&quot;&gt;Ethical Approval&lt;/hd&gt; &lt;p&gt;The study was approved by the institute ethics committee (IECPG‑218/21.06.2018).&lt;/p&gt; &lt;hd id=&quot;AN0191290301-17&quot;&gt;Conflict of Interests&lt;/hd&gt; &lt;p&gt;None.&lt;/p&gt; &lt;hd id=&quot;AN0191290301-18&quot;&gt;Abbreviations&lt;/hd&gt; &lt;p&gt;&lt;/p&gt; &lt;p&gt;• AGE&lt;/p&gt; &lt;p&gt;&lt;/p&gt; &lt;ulist&gt; &lt;item&gt; Advanced glycated end poducts&lt;/item&gt; &lt;p&gt;&lt;/p&gt; &lt;/ulist&gt; &lt;p&gt;• ASD&lt;/p&gt; &lt;p&gt;&lt;/p&gt; &lt;ulist&gt; &lt;item&gt; Autism spectrum disorder&lt;/item&gt; &lt;p&gt;&lt;/p&gt; &lt;/ulist&gt; &lt;p&gt;• CARS-2&lt;/p&gt; &lt;p&gt;&lt;/p&gt; &lt;ulist&gt; &lt;item&gt; Childhood Autism Rating Scale 2&lt;/item&gt; &lt;p&gt;&lt;/p&gt; &lt;/ulist&gt; &lt;p&gt;• CDC&lt;/p&gt; &lt;p&gt;&lt;/p&gt; &lt;ulist&gt; &lt;item&gt; Centers for disease control and prevention&lt;/item&gt; &lt;p&gt;&lt;/p&gt; &lt;/ulist&gt; &lt;p&gt;• CBCL&lt;/p&gt; &lt;p&gt;&lt;/p&gt; &lt;ulist&gt; &lt;item&gt; Childhood behavioural check list&lt;/item&gt; &lt;p&gt;&lt;/p&gt; &lt;/ulist&gt; &lt;p&gt;• CSP-2&lt;/p&gt; &lt;p&gt;&lt;/p&gt; &lt;ulist&gt; &lt;item&gt; Child sensory profile-2&lt;/item&gt; &lt;p&gt;&lt;/p&gt; &lt;/ulist&gt; &lt;p&gt;• CMA&lt;/p&gt; &lt;p&gt;&lt;/p&gt; &lt;ulist&gt; &lt;item&gt; Nω-carboxymethylarginine&lt;/item&gt; &lt;p&gt;&lt;/p&gt; &lt;/ulist&gt; &lt;p&gt;• CML&lt;/p&gt; &lt;p&gt;&lt;/p&gt; &lt;ulist&gt; &lt;item&gt; Nε-carboxymethyllysine&lt;/item&gt; &lt;p&gt;&lt;/p&gt; &lt;/ulist&gt; &lt;p&gt;• DALY&lt;/p&gt; &lt;p&gt;&lt;/p&gt; &lt;ulist&gt; &lt;item&gt; Disability adjusted life year&lt;/item&gt; &lt;p&gt;&lt;/p&gt; &lt;/ulist&gt; &lt;p&gt;• DNA&lt;/p&gt; &lt;p&gt;&lt;/p&gt; &lt;ulist&gt; &lt;item&gt; Deoxyribonucleic acid&lt;/item&gt; &lt;p&gt;&lt;/p&gt; &lt;/ulist&gt; &lt;p&gt;• DP-3&lt;/p&gt; &lt;p&gt;&lt;/p&gt; &lt;ulist&gt; &lt;item&gt; Developmental profile 3&lt;/item&gt; &lt;p&gt;&lt;/p&gt; &lt;/ulist&gt; &lt;p&gt;• DSM V&lt;/p&gt; &lt;p&gt;&lt;/p&gt; &lt;ulist&gt; &lt;item&gt; Diagnostic and statistical manual of mental disorders 5th edition&lt;/item&gt; &lt;p&gt;&lt;/p&gt; &lt;/ulist&gt; &lt;p&gt;• DT&lt;/p&gt; &lt;p&gt;&lt;/p&gt; &lt;ulist&gt; &lt;item&gt; Dityrosine&lt;/item&gt; &lt;p&gt;&lt;/p&gt; &lt;/ulist&gt; &lt;p&gt;• EDTA&lt;/p&gt; &lt;p&gt;&lt;/p&gt; &lt;ulist&gt; &lt;item&gt; Ethylenediaminetetra-acetic acid&lt;/item&gt; &lt;p&gt;&lt;/p&gt; &lt;/ulist&gt; &lt;p&gt;• HPLC&lt;/p&gt; &lt;p&gt;&lt;/p&gt; &lt;ulist&gt; &lt;item&gt; High performance liquid chromatography&lt;/item&gt; &lt;p&gt;&lt;/p&gt; &lt;/ulist&gt; &lt;p&gt;• INCLEN&lt;/p&gt; &lt;p&gt;&lt;/p&gt; &lt;ulist&gt; &lt;item&gt; International clinical epidemiology network&lt;/item&gt; &lt;p&gt;&lt;/p&gt; &lt;item&gt; INDT-ASD&lt;/item&gt; &lt;p&gt;&lt;/p&gt; &lt;item&gt; INCLEN Diagnostic Tool for Autism Spectrum Disorder&lt;/item&gt; &lt;p&gt;&lt;/p&gt; &lt;/ulist&gt; &lt;p&gt;• IQ&lt;/p&gt; &lt;p&gt;&lt;/p&gt; &lt;ulist&gt; &lt;item&gt; Intelligence quotient&lt;/item&gt; &lt;p&gt;&lt;/p&gt; &lt;/ulist&gt; &lt;p&gt;• ISAA&lt;/p&gt; &lt;p&gt;&lt;/p&gt; &lt;ulist&gt; &lt;item&gt; Indian Scale for Assessment of Autism&lt;/item&gt; &lt;p&gt;&lt;/p&gt; &lt;/ulist&gt; &lt;p&gt;• M-CHAT&lt;/p&gt; &lt;p&gt;&lt;/p&gt; &lt;ulist&gt; &lt;item&gt; Modified Checklist for Autism in Toddlers&lt;/item&gt; &lt;p&gt;&lt;/p&gt; &lt;/ulist&gt; &lt;p&gt;• MTHFR&lt;/p&gt; &lt;p&gt;&lt;/p&gt; &lt;ulist&gt; &lt;item&gt; Methylene tetrahydrofolate reductase&lt;/item&gt; &lt;p&gt;&lt;/p&gt; &lt;/ulist&gt; &lt;p&gt;• PCR&lt;/p&gt; &lt;p&gt;&lt;/p&gt; &lt;ulist&gt; &lt;item&gt; Polymerase chain reaction&lt;/item&gt; &lt;p&gt;&lt;/p&gt; &lt;/ulist&gt; &lt;p&gt;• RNA&lt;/p&gt; &lt;p&gt;&lt;/p&gt; &lt;ulist&gt; &lt;item&gt; Ribonucleic acid&lt;/item&gt; &lt;p&gt;&lt;/p&gt; &lt;/ulist&gt; &lt;p&gt;• ROS&lt;/p&gt; &lt;p&gt;&lt;/p&gt; &lt;ulist&gt; &lt;item&gt; Reactive oxygen species&lt;/item&gt; &lt;p&gt;&lt;/p&gt; &lt;/ulist&gt; &lt;p&gt;• TDC&lt;/p&gt; &lt;p&gt;&lt;/p&gt; &lt;ulist&gt; &lt;item&gt; Typically developing children&lt;/item&gt; &lt;p&gt;&lt;/p&gt; &lt;/ulist&gt; &lt;p&gt;• VABS&lt;/p&gt; &lt;p&gt;&lt;/p&gt; &lt;ulist&gt; &lt;item&gt; Vineland adaptive behaviour scale&lt;/item&gt; &lt;/ulist&gt; &lt;hd id=&quot;AN0191290301-19&quot;&gt;Publisher&#39;s Note&lt;/hd&gt; &lt;p&gt;Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.&lt;/p&gt; &lt;ref id=&quot;AN0191290301-20&quot;&gt; 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  Group: Ti
  Data: Transmethylation and Oxidative Biomarkers in Children with Autism Spectrum Disorder: A Cross Sectional Study
– Name: Language
  Label: Language
  Group: Lang
  Data: English
– Name: Author
  Label: Authors
  Group: Au
  Data: &lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Sheffali+Gulati%22&quot;&gt;Sheffali Gulati&lt;/searchLink&gt; (ORCID &lt;externalLink term=&quot;http://orcid.org/0000-0003-1439-9959&quot;&gt;0000-0003-1439-9959&lt;/externalLink&gt;)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Chinthana+L%2E+Narayan%22&quot;&gt;Chinthana L. Narayan&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Aakash+Mahesan%22&quot;&gt;Aakash Mahesan&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Gautam+Kamila%22&quot;&gt;Gautam Kamila&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Seema+Kapoor%22&quot;&gt;Seema Kapoor&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Pradeep+K%2E+Chaturvedi%22&quot;&gt;Pradeep K. Chaturvedi&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Vinod+Scaria%22&quot;&gt;Vinod Scaria&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Thirumurthy+Velpandian%22&quot;&gt;Thirumurthy Velpandian&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Prashant+Jauhari%22&quot;&gt;Prashant Jauhari&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Biswaroop+Chakrabarty%22&quot;&gt;Biswaroop Chakrabarty&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Sudip+K%2E+R%2E+Datta%22&quot;&gt;Sudip K. R. Datta&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22R%2E+M%2E+Pandey%22&quot;&gt;R. M. Pandey&lt;/searchLink&gt;
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  Data: &lt;searchLink fieldCode=&quot;SO&quot; term=&quot;%22Journal+of+Autism+and+Developmental+Disorders%22&quot;&gt;&lt;i&gt;Journal of Autism and Developmental Disorders&lt;/i&gt;&lt;/searchLink&gt;. 2026 56(1):269-277.
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  Data: Springer. Available from: Springer Nature. One New York Plaza, Suite 4600, New York, NY 10004. Tel: 800-777-4643; Tel: 212-460-1500; Fax: 212-460-1700; e-mail: customerservice@springernature.com; Web site: https://link.springer.com/
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  Data: Y
– Name: Pages
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  Data: 9
– Name: DatePubCY
  Label: Publication Date
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  Data: 2026
– Name: TypeDocument
  Label: Document Type
  Group: TypDoc
  Data: Journal Articles&lt;br /&gt;Reports - Research
– Name: Subject
  Label: Descriptors
  Group: Su
  Data: &lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22Autism+Spectrum+Disorders%22&quot;&gt;Autism Spectrum Disorders&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22Metabolism%22&quot;&gt;Metabolism&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22Physiology%22&quot;&gt;Physiology&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22Children%22&quot;&gt;Children&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22Severity+%28of+Disability%29%22&quot;&gt;Severity (of Disability)&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22Perceptual+Impairments%22&quot;&gt;Perceptual Impairments&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22Behavior+Problems%22&quot;&gt;Behavior Problems&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22Correlation%22&quot;&gt;Correlation&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22Biochemistry%22&quot;&gt;Biochemistry&lt;/searchLink&gt;
– Name: SubjectThesaurus
  Label: Assessment and Survey Identifiers
  Group: Su
  Data: &lt;searchLink fieldCode=&quot;SU&quot; term=&quot;%22Childhood+Autism+Rating+Scale%22&quot;&gt;Childhood Autism Rating Scale&lt;/searchLink&gt;
– Name: DOI
  Label: DOI
  Group: ID
  Data: 10.1007/s10803-024-06542-9
– Name: ISSN
  Label: ISSN
  Group: ISSN
  Data: 0162-3257&lt;br /&gt;1573-3432
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: We aimed to investigate the potential role of biomarkers of transmethylation, oxidative stress, and mitochondrial dysfunction in children with Autism Spectrum Disorder (ASD) by comparing them with that of typically developing children (TDC) controls. We also tried to correlate them with severity of autism, sensory issues, behavioural comorbidities and developmental quotients 119 with ASD and 52 age and sex matched typically developing children (TDC) controls were enrolled excluding those with chronic-illness or on any antioxidant therapy/multivitamins/anti-epileptic drugs. Median levels of biomarkers - serum homocysteine, cysteine, methionine, urine uric acid-to-creatinine ratio, arterial lactate, serum vitamin E, vitamin B12, folate, Nε-carboxymethyllysine, Nω- carboxymethylarginine (CMA), dityrosine and MTHFR C677T polymorphism were calculated. Children with ASD were further characterised using Childhood Autism Rating Scale-2, Childhood behavioural checklist, child sensory profile 2 caregiver questionnaire, Developmental Profile 3 for any correlation with the various biomarker levels. The median level of serum homocysteine in ASD group was 9 μmol/L(Range, 7- 16μmol/L), which was significantly higher than controls 7 μmol/L(Range, 4- 11μmol/L)(p=0.01). The prevalence of hyper-homocystinemia(&gt;15μmol/L) was 13.4% in ASD as compared to 3.8% in controls with a significant difference(p=0.04). Dityrosine level was higher among ASD children when compared to TDC (9.8 vs 2.2 counts per second(cps), p&lt;0.001). No significant correlation was found between prevalence of hyperhomocysteinemia and severity of autism/DQ/behavioural issues. No significant difference was found between the median levels of other biomarkers. Results support possible role of transmethylation defects and oxidative stress in ASD pathogenesis. Further studies are warranted for a better understanding of ASD pathogenesis.
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  Label: Abstractor
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  Data: As Provided
– Name: DateEntry
  Label: Entry Date
  Group: Date
  Data: 2026
– Name: AN
  Label: Accession Number
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  Data: EJ1504714
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=eric&AN=EJ1504714
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1007/s10803-024-06542-9
    Languages:
      – Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 9
        StartPage: 269
    Subjects:
      – SubjectFull: Autism Spectrum Disorders
        Type: general
      – SubjectFull: Metabolism
        Type: general
      – SubjectFull: Physiology
        Type: general
      – SubjectFull: Children
        Type: general
      – SubjectFull: Severity (of Disability)
        Type: general
      – SubjectFull: Perceptual Impairments
        Type: general
      – SubjectFull: Behavior Problems
        Type: general
      – SubjectFull: Correlation
        Type: general
      – SubjectFull: Biochemistry
        Type: general
      – SubjectFull: Childhood Autism Rating Scale
        Type: general
    Titles:
      – TitleFull: Transmethylation and Oxidative Biomarkers in Children with Autism Spectrum Disorder: A Cross Sectional Study
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Sheffali Gulati
      – PersonEntity:
          Name:
            NameFull: Chinthana L. Narayan
      – PersonEntity:
          Name:
            NameFull: Aakash Mahesan
      – PersonEntity:
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            NameFull: Gautam Kamila
      – PersonEntity:
          Name:
            NameFull: Seema Kapoor
      – PersonEntity:
          Name:
            NameFull: Pradeep K. Chaturvedi
      – PersonEntity:
          Name:
            NameFull: Vinod Scaria
      – PersonEntity:
          Name:
            NameFull: Thirumurthy Velpandian
      – PersonEntity:
          Name:
            NameFull: Prashant Jauhari
      – PersonEntity:
          Name:
            NameFull: Biswaroop Chakrabarty
      – PersonEntity:
          Name:
            NameFull: Sudip K. R. Datta
      – PersonEntity:
          Name:
            NameFull: R. M. Pandey
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          Dates:
            – D: 01
              M: 01
              Type: published
              Y: 2026
          Identifiers:
            – Type: issn-print
              Value: 0162-3257
            – Type: issn-electronic
              Value: 1573-3432
          Numbering:
            – Type: volume
              Value: 56
            – Type: issue
              Value: 1
          Titles:
            – TitleFull: Journal of Autism and Developmental Disorders
              Type: main
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