{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T23:32:54Z","timestamp":1783467174173,"version":"3.55.0"},"reference-count":14,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T00:00:00Z","timestamp":1620259200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The current diagnostic work\u2010up of inborn errors of metabolism (IEM) is rapidly moving toward integrative analytical approaches. We aimed to develop an innovative, targeted urine metabolomics (TUM) screening procedure to accelerate the diagnosis of patients with IEM. Urinary samples, spiked with three stable isotope\u2010labeled internal standards, were analyzed for 258 diagnostic metabolites with an ultra\u2010high performance liquid chromatography\u2010quadrupole time\u2010of\u2010flight mass spectrometry (UHPLC\u2010QTOF\u2010MS) configuration run in positive and negative ESI modes. The software automatically annotated peaks, corrected for peak overloading, and reported peak quality and shifting. Robustness and reproducibility were satisfactory for most metabolites. Z\u2010scores were calculated against four age\u2010group\u2010matched control cohorts. Disease phenotypes were scored based on database metabolite matching. Graphical reports comprised a needle plot, annotating abnormal metabolites, and a heatmap showing the prioritized disease phenotypes. In the clinical validation, we analyzed samples of 289 patients covering 78 OMIM phenotypes from 12 of the 15 society for the study of inborn errors of metabolism (SSIEM) disease groups. The disease groups include disorders in the metabolism of amino acids, fatty acids, ketones, purines and pyrimidines, carbohydrates, porphyrias, neurotransmitters, vitamins, cofactors, and creatine. The reporting tool easily and correctly diagnosed most samples. Even subtle aberrant metabolite patterns as seen in mild multiple acyl\u2010CoA dehydrogenase deficiency (GAII) and maple syrup urine disease (MSUD) were correctly called without difficulty. Others, like creatine transporter deficiency, are illustrative of IEM that remain difficult to diagnose. We present TUM as a powerful diagnostic screening tool that merges most urinary diagnostic assays expediting the diagnostics for patients suspected of an IEM.<\/jats:p>","DOI":"10.1002\/jimd.12385","type":"journal-article","created":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T06:54:34Z","timestamp":1618210474000},"page":"1113-1123","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Targeted urine metabolomics with a graphical reporting tool for rapid diagnosis of inborn errors of metabolism"],"prefix":"10.1002","volume":"44","author":[{"given":"Laura K.M.","family":"Steinbusch","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics Maastricht University Medical Center  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Maastricht University Medical Center  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huub W.A.H.","family":"Waterval","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Maastricht University Medical Center  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fons A.P.M.","family":"Stassen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Maastricht University Medical Center  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karlien L.M.","family":"Coene","sequence":"additional","affiliation":[{"name":"Translational Metabolic Laboratory, Department of Laboratory Medicine Radboud University Medical Centre  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udo F.H.","family":"Engelke","sequence":"additional","affiliation":[{"name":"Translational Metabolic Laboratory, Department of Laboratory 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