BACKGROUND: Long acknowledged for influencing physiological processes, heavy metals are being explored as potential remedies for various diseases. Imbalances in specific metals and essential micronutrients pose a risk for neurodevelopmental disorders (NDDs).

OBJECTIVES: To analyse the levels of heavy metals and essential micronutrients, along with molecular analysis, in various tissues of children with NDDs.

METHODS: This is an ongoing observational study, where children with cerebral palsy(CP:2-18 years), ADHD(6-18 years), Autism Spectrum Disorder(ASD:1.5-18 years), and controls[(IQ>70)( 1.5-18 years) were enrolled. Children on exclusion diets, chelating agents, chronic systemic diseases, behavioural or motor impairment were excluded. Blood, urine, hair, and nail samples underwent analysis for 21 heavy metals and trace elements. Additionally, an OMICs-based approach examined the molecular drivers of ADHD, CP, and AD through SNP, transcriptome, and methylation analyses.

RESULTS: In a study with N=610 participants(62% males, mean age 7.35±3.36 years), significant variations in Magnesium, Beryllium, Vanadium, Chromium, Manganese, Cobalt, Nickel, Cadmium, and Lead were observed across ASD, ADHD, CP, and control groups in all four tissues [P<0.05]. Autistic children exhibited notably high levels of lead in blood (47%) and urine (40%). Molecular analysis revealed differential methylation of genes associated with neuronal development pathways (SGCE, ZDHHC3, HMGA1, SYT2, PRCC2) in ASD, along with distinctive methylation patterns in ADHD and CP.

CONCLUSION: Imbalance of toxic metals and deficiency in essential elements in children with NDDs may trigger molecular-level pathogenic mechanisms. Transcriptome analysis revealed enriched pathways in cellular metabolism, neuronal development, and stress responses, requiring further validation for their contribution to disease pathology.

Sheffali Gulati
All India Institute of Medical Sciences
India

Javed Ahsan Quadri
All India Institute of Medical Sciences
India

Subhradip Karmakar
All India Institute of Medical Sciences
India

Pranjal Sisodia
All India Institute of Medical Sciences
India

Sakshi Ojha
All India Institute of Medical Sciences
India

Gautam Kamila
All India Institute of Medical Sciences
India

Shivam Pandey
All India Institute of Medical Sciences
India

Shariff Ahmadulla
All India Institute of Medical Sciences
India