{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T13:55:18Z","timestamp":1780926918892,"version":"3.54.1"},"reference-count":62,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T00:00:00Z","timestamp":1716508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Deanship of Scientific Research, King Saud"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Currently, tandem mass spectrometry-based newborn screening (NBS), which examines targeted biomarkers, is the first approach used for the early detection of maple syrup urine disease (MSUD) in newborns, followed by confirmatory genetic mutation tests. However, these diagnostic approaches have limitations, demanding the development of additional tools for the diagnosis\/screening of MUSD. Recently, untargeted metabolomics has been used to explore metabolic profiling and discover the potential biomarkers\/pathways of inherited metabolic diseases. Thus, we aimed to discover a distinctive metabolic profile and biomarkers\/pathways for MSUD newborns using untargeted metabolomics. Herein, untargeted metabolomics was used to analyze dried blood spot (DBS) samples from 22 MSUD and 22 healthy control newborns. Our data identified 210 altered endogenous metabolites in MSUD newborns and new potential MSUD biomarkers, particularly L-alloisoleucine, methionine, and lysoPI. In addition, the most impacted pathways in MSUD newborns were the ascorbate and aldarate pathways and pentose and glucuronate interconversions, suggesting that oxidative and detoxification events may occur in early life. Our approach leads to the identification of new potential biomarkers\/pathways that could be used for the early diagnosis\/screening of MSUD newborns but require further validation studies. Our untargeted metabolomics findings have undoubtedly added new insights to our understanding of the pathogenicity of MSUD, which helps us select the appropriate early treatments for better health outcomes.<\/jats:p>","DOI":"10.3390\/ijms25115720","type":"journal-article","created":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T08:30:22Z","timestamp":1716539422000},"page":"5720","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Exploratory Untargeted Metabolomics of Dried Blood Spot Samples from Newborns with Maple Syrup Urine Disease"],"prefix":"10.3390","volume":"25","author":[{"given":"Abeer Z.","family":"Alotaibi","sequence":"first","affiliation":[{"name":"Genome Research Chair, Department of Biochemistry, College of Science, King Saud University, P.O. Box 22452, Riyadh 11652, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reem H.","family":"AlMalki","sequence":"additional","affiliation":[{"name":"Metabolomics Section, Department of Clinical Genomics, Center for Genomics Medicine, King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha","family":"Al Mogren","sequence":"additional","affiliation":[{"name":"Metabolomics Section, Department of Clinical Genomics, Center for Genomics Medicine, King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3638-8716","authenticated-orcid":false,"given":"Rajaa","family":"Sebaa","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratories, College of Applied Medical Sciences, Shaqra University, Shaqra 11961, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Alanazi","sequence":"additional","affiliation":[{"name":"Genome Research Chair, Department of Biochemistry, College of Science, King Saud University, P.O. Box 22452, Riyadh 11652, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minnie","family":"Jacob","sequence":"additional","affiliation":[{"name":"Metabolomics Section, Department of Clinical Genomics, Center for Genomics Medicine, King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahamd","family":"Alodaib","sequence":"additional","affiliation":[{"name":"Metabolomics Section, Department of Clinical Genomics, Center for Genomics Medicine, King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Alfares","sequence":"additional","affiliation":[{"name":"Metabolomics Section, Department of Clinical Genomics, Center for Genomics Medicine, King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9527-9424","authenticated-orcid":false,"given":"Anas M.","family":"Abdel Rahman","sequence":"additional","affiliation":[{"name":"Metabolomics Section, Department of Clinical Genomics, Center for Genomics Medicine, King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh 11211, Saudi Arabia"},{"name":"Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"592","DOI":"10.2174\/1871530321666201223110918","article-title":"Occurrence of Inborn Errors of Metabolism in Newborns, Diagnosis and Prophylaxis","volume":"21","author":"Bharadwaj","year":"2021","journal-title":"Endocr. 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