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The objectives included establishing population-specific cutoff values for selected metals and examining their correlation with ASD symptom and severity. A national, facility-based comparative study was conducted across eight Egyptian governorates. It included 455 children with clinically confirmed ASD and 230 age- and sex-matched typically developing relatives. ASD diagnoses were established using DSM-5 criteria and the Gilliam Autism Rating Scale, Second Edition (GARS-2). Hair samples were collected and analyzed for five toxic metals; aluminum (Al), arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) using inductively coupled plasma mass spectrometry (ICP-MS). Receiver operating characteristic (ROC) curve analysis was applied to determine optimal diagnostic cutoffs. Sensitivity, specificity, and predictive values were calculated. Correlation analyses were conducted to evaluate the association between metal levels and ASD severity. Children with ASD had significantly elevated hair levels of Al, As, Cd, and Pb compared to typically developing controls. Hg levels were statistically insignificant higher in the ASD group. Al showed the strongest diagnostic performance with 89.4% sensitivity and a cutoff\u2009\u2265\u200910.35\u00a0ppm. Proposed cutoff values for the other metals were: As\u2009\u2265\u20090.10\u00a0ppm, Cd\u2009\u2265\u20090.10\u00a0ppm, Hg\u2009\u2265\u20090.31\u00a0ppm, and Pb\u2009\u2265\u20091.87\u00a0ppm. Only Al levels were positively correlated with ASD severity. Hair-based toxic metal profiling, particularly of Al, may support early ASD risk detection. However, it should be integrated within a broader diagnostic framework that includes clinical, behavioral, and environmental assessments.<\/jats:p>","DOI":"10.1007\/s12011-025-04877-7","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T03:13:03Z","timestamp":1762744383000},"page":"3075-3089","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Diagnostic Utility of Hair Toxic Metals in Autism Spectrum Disorder: Unlocking Biomarkers Among Egyptian Children"],"prefix":"10.1007","volume":"204","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0575-5202","authenticated-orcid":false,"given":"Ammal M.","family":"Metwally","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarek M. 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Written informed consent was obtained from the parents or legal guardians of all participating children. For individuals unable to write, a right thumbprint was used in lieu of a signature. Participation was entirely voluntary, and all data were collected confidentially. Personal identifiers were removed, and records were securely stored. The study adhered to the International Ethical Guidelines for Biomedical Research Involving Human Subjects [\n                      \n                      ]. 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