Dataset Information

Interrelation between homocysteine metabolism and the development of autism spectrum disorder in children.

ABSTRACT: Evidence is emerging that dysregulation of circulating concentrations of homocysteine, an important intermediate in folate and vitamin B12 metabolism, is associated with autism spectrum disorder (ASD), but comprehensive assessments and correlations with disease characteristics have not been reported. Multivariate ordinal regression and restricted cubic spline (RCS) models were used to estimate independent correlations between serum homocysteine, folate, and vitamin B12 levels and clinical outcomes and severity of children with ASD. After adjusting for confounding factors, serum homocysteine levels were significantly higher in children with ASD than in healthy controls (β: 0.370; 95% CI: 0.299~0.441, p < 0.001). Moreover, homocysteine had a good diagnostic ability for distinguishing children with ASD from healthy subjects (AUC: 0.899, p < 0.001). The RCS model indicated a positive and linear association between serum homocysteine and the risk of ASD. The lowest quartile of folate was positively associated with ASD severity (OR: 4.227, 95% CI: 1.022~17.488, p = 0.041) compared to the highest quartile, and serum folate showed a negative and linear association with ASD severity. In addition, decreased concentrations of folate and vitamin B12 were associated with poor adaptive behavior developmental quotients of the Gesell Developmental Schedules (p < 0.05). Overall, an increased homocysteine level was associated with ASD in a linear manner and is thus a novel diagnostic biomarker for ASD. Decreased concentrations of folate and vitamin B12 were associated with poor clinical profiles of children with ASD. These findings suggest that homocysteine-lowering interventions or folate and vitamin B12 supplementation might be a viable treatment strategy for ASD.

SUBMITTER: Li B

PROVIDER: S-EPMC9421079 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Interrelation between homocysteine metabolism and the development of autism spectrum disorder in children.

Li Bingbing B Xu Yiran Y Pang Dizhou D Zhao Qiang Q Zhang Lingling L Li Ming M Li Wenhua W Duan Guiqin G Zhu Changlian C

Frontiers in molecular neuroscience 20220815

Evidence is emerging that dysregulation of circulating concentrations of homocysteine, an important intermediate in folate and vitamin B12 metabolism, is associated with autism spectrum disorder (ASD), but comprehensive assessments and correlations with disease characteristics have not been reported. Multivariate ordinal regression and restricted cubic spline (RCS) models were used to estimate independent correlations between serum homocysteine, folate, and vitamin B12 levels and clinical outcom ...[more]

PMID: 36046711

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Project description:Creatine deficiency syndrome (CDS) comprises three separate enzyme deficiencies with overlapping clinical presentations: arginine:glycine amidinotransferase (GATM gene, glycine amidinotransferase), guanidinoacetate methyltransferase (GAMT gene), and creatine transporter deficiency (SLC6A8 gene, solute carrier family 6 member 8). CDS presents with developmental delays/regression, intellectual disability, speech and language impairment, autistic behaviour, epileptic seizures, treatment-refractory epilepsy, and extrapyramidal movement disorders; symptoms that are also evident in children with autism. The objective of the study was to test the hypothesis that genetic variability in creatine metabolism genes is associated with autism. We sequenced GATM, GAMT and SLC6A8 genes in 166 patients with autism (coding sequence, introns and adjacent untranslated regions). A total of 29, 16 and 25 variants were identified in each gene, respectively. Four variants were novel in GATM, and 5 in SLC6A8 (not present in the 1000 Genomes, Exome Sequencing Project (ESP) or Exome Aggregation Consortium (ExAC) databases). A single variant in each gene was identified as non-synonymous, and computationally predicted to be potentially damaging. Nine variants in GATM were shown to have a lower minor allele frequency (MAF) in the autism population than in the 1000 Genomes database, specifically in the East Asian population (Fisher's exact test). Two variants also had lower MAFs in the European population. In summary, there were no apparent associations of variants in GAMT and SLC6A8 genes with autism. The data implying there could be a lower association of some specific GATM gene variants with autism is an observation that would need to be corroborated in a larger group of autism patients, and with sub-populations of Asian ethnicities. Overall, our findings suggest that the genetic variability of creatine synthesis/transport is unlikely to play a part in the pathogenesis of autism spectrum disorder (ASD) in children.

Project description:This project investigated the genetic and metabolic profiles of Lebanese children and adolescents with Autism Spectrum Disorder (ASD) to better understand the disorder’s etiology and identify potential biomarkers. Specifically, the study focused on methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms (rs1801133 and rs1801131) and their relationship with homocysteine metabolism, as well as plasma levels of vitamin B9, vitamin B12, glucose, and lipid profiles. A total of 172 participants (86 individuals with ASD and 86 age-, sex-, and region-matched neurotypical controls) aged between 3 and 18 years were recruited across Lebanon between June 2022 and June 2023. ASD diagnosis was confirmed using DSM-5 criteria and the Childhood Autism Rating Scale (CARS). Blood samples were collected under fasting conditions to measure biochemical parameters (homocysteine, vitamin B9, vitamin B12, glucose, lipid panel), while DNA was extracted for genotyping of the MTHFR variants using PCR and Sanger sequencing. The results revealed that while the MTHFR rs1801133 and rs1801131 polymorphisms were not significantly associated with ASD risk, individuals with ASD had significantly higher homocysteine levels and lower vitamin B9 concentrations compared to controls. Vitamin B12, glucose, and lipid concentrations showed no significant group differences. However, the TT genotype of the rs1801133 variant was strongly associated with elevated homocysteine levels among individuals with ASD. These findings suggest that hyperhomocysteinemia and folate deficiency may contribute to the pathophysiology of ASD, highlighting their potential role as metabolic biomarkers. Although no direct genetic association was observed between MTHFR variants and ASD susceptibility in the Lebanese population, the correlation between the rs1801133 TT genotype and elevated homocysteine underscores the importance of integrating genetic and metabolic data. This work represents the first Lebanese case-control study combining genetic and biochemical approaches to ASD. It emphasizes the need for further research on metabolic pathways, nutritional interventions (particularly folate supplementation), and additional enzymes involved in homocysteine metabolism. Ultimately, this project aims to contribute to the development of personalized intervention strategies and improve understanding of ASD within the Middle Eastern context.

Project description:Objective: Children with autism spectrum disorder (ASD) experience significant challenges with their motor coordination. It is not, however, well understood how motor coordination may impact the behavioral functioning of children with ASD. Therefore the purpose of this study was to explore the relationships between motor coordination and adaptive behavior in 7-12-year-old children with ASD. Methods: Motor coordination was assessed using the Movement Assessment Battery for Children, 2nd Edition (MABC-2) and adaptive behavior was assessed by parental report using the Vineland Adaptive Behavior Scales, 2nd Edition (VABS-2) as part of a larger cross-sectional study. Descriptive characteristics were calculated for MABC-2 and VABS-2 scores and Spearman's rank order correlation analyses were used to examine the relationship between motor coordination and adaptive behavior. Results: On average, the participants (n = 26) exhibited significant challenges in regard to their motor coordination with all but two participants classified as having significant motor impairments by scoring at or below the 16th percentile on the MABC-2. Results from the correlation analyses indicated that manual dexterity was positively related to daily living skills (? = 0.58, p < 0.003), and overall motor coordination was positively related to daily living skills (? = 0.60, p < 0.003) and overall adaptive behavior (? = 0.57, p < 0.003). In all instances, better motor coordination was related to more adaptive behaviors. Conclusion: These results highlight the profound motor coordination challenges that children with ASD experience and also suggest that these challenges, particularly with manual dexterity, are related to the daily behavior of children with ASD. The interrelatedness of motor and adaptive behavior suggests the need to further explore the impact of motor-based interventions for this population, as well as conduct longitudinal studies to disentangle these relationships.

Dataset Information

Interrelation between homocysteine metabolism and the development of autism spectrum disorder in children.

Publications

Interrelation between homocysteine metabolism and the development of autism spectrum disorder in children.

Similar Datasets

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