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Metabolic profiles were analyzed using the non-derivatized MS\/MS Kit, and genetic mutations were identified via next-generation sequencing and confirmed by Sanger sequencing. Receiver Operating Characteristic (ROC) analysis evaluated the predictive value of amino acids and acylcarnitines in dried blood spots (DBS) for identifying missed patients including 40 missed patients and 17,269 healthy individuals, with additional validation using 12 missed patients and 454 healthy controls.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The age of diagnosis was significantly higher in the \u201cMissed Screening\u201d group compared to the \u201cNewborn Screening\u201d group (74.50 vs. 18.00\u00a0days, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). ROC analysis revealed that citrulline had excellent diagnostic accuracy for missed patients, with an AUC of 0.970 and a cut-off value of 17.57\u00a0\u00b5mol\/L. Additionally, glycine, phenylalanine, ornithine, and C8 were significant markers, each with an AUC greater than 0.70. A combination of these markers achieved an AUC of 0.996 with a cut-off value of 0.00195. Validation demonstrated a true positive rate of 91.67% and a true negative rate of 96.48%. Common <jats:italic>SLC25A13<\/jats:italic> mutations in both groups were c.852_855del, IVS16ins3kb, and c.615\u2009+\u20095G\u2009&gt;\u2009A.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Combining multiple metabolic markers during NBS significantly improves sensitivity and specificity for detecting missed NICCD cases. However, the relationship between genetic mutations and missed cases remains unclear.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13023-025-03532-7","type":"journal-article","created":{"date-parts":[[2025,1,11]],"date-time":"2025-01-11T08:25:53Z","timestamp":1736583953000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Enhancing newborn screening sensitivity and specificity for missed NICCD using selected amino acids and acylcarnitines"],"prefix":"10.1186","volume":"20","author":[{"given":"Peiyao","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingwei","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhe","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duo","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shasha","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyan","family":"Cen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qimin","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benqing","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1124-7044","authenticated-orcid":false,"given":"Xinwen","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,11]]},"reference":[{"issue":"6","key":"3532_CR1","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1007\/s10038-008-0282-2","volume":"53","author":"A Tabata","year":"2008","unstructured":"Tabata A, Sheng J-S, Ushikai M, Song Y-Z, Gao H-Z, Lu Y-B, et al. 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Written consents were obtained from parents for sample collection and data publication.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"We confirm that the family has signed a written informed consent for the publication of their children\u2019s genetic data, clinical details, and\/or any accompanying images.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"17"}}