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This study aimed to gain insight into the underlying mechanisms of neural dysfunction. Here we analyzed the expression of brain-derived neurotrophic factor (BDNF) and 10 genes required for correct brain functioning in plasma and blood of patients with Urea Cycle Disorders (UCD), Maple Syrup Urine Disease (MSUD) and controls. Receiver-operating characteristic (ROC) analysis was used to evaluate sensitivity and specificity of potential biomarkers. <jats:italic>CACNA2D2<\/jats:italic> (\u03b12\u03b42 subunit of voltage-gated calcium channels) and <jats:italic>MECP2<\/jats:italic> (methyl-CpG binding protein 2) mRNA and protein showed an excellent neural function biomarker signature (AUC\u2009\u2265\u20090,925) for recognition of MSUD. <jats:italic>THBS3<\/jats:italic> (thrombospondin 3) mRNA and AABA gave a very good biomarker signature (AUC 0,911) for executive-attention deficits. <jats:italic>THBS3<\/jats:italic>, <jats:italic>LIN28A<\/jats:italic> mRNA, and alanine showed a perfect biomarker signature (AUC 1) for behavioral and mood disorders. Finally, a panel of BDNF protein and at least two large neural AAs showed a perfect biomarker signature (AUC 1) for recognition of psychomotor delay, pointing to excessive protein restriction as central causative of psychomotor delay. To conclude, our study has identified promising biomarker panels for neural function evaluation, providing a base for future studies with larger samples.<\/jats:p>","DOI":"10.1038\/s41598-019-45674-2","type":"journal-article","created":{"date-parts":[[2019,6,24]],"date-time":"2019-06-24T10:03:22Z","timestamp":1561370602000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Discovery of Biomarker Panels for Neural Dysfunction in Inborn Errors of Amino Acid Metabolism"],"prefix":"10.1038","volume":"9","author":[{"given":"Alba-Aina","family":"Castells","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Gueraldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafel","family":"Balada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alba","family":"Trist\u00e1n-Noguero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisenda","family":"Cort\u00e8s-Saladelafont","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Ramos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Meavilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariela","family":"De Los Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila","family":"Garcia-Volpe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roser","family":"Colom\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Luz","family":"Couce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Sierra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida","family":"Ormaz\u00e1bal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Batllori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3422-9685","authenticated-orcid":false,"given":"Rafael","family":"Artuch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Armstrong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soledad","family":"Alc\u00e1ntara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9853-688X","authenticated-orcid":false,"given":"\u00c0ngels","family":"Garcia-Cazorla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,6,24]]},"reference":[{"key":"45674_CR1","doi-asserted-by":"publisher","first-page":"1356","DOI":"10.1126\/science.14400","volume":"195","author":"A Martinez-Hernandez","year":"1977","unstructured":"Martinez-Hernandez, A., Bell, K. 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