{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T09:04:24Z","timestamp":1784624664252,"version":"3.55.0"},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005941","name":"Dietmar Hopp Stiftung","doi-asserted-by":"publisher","award":["23011222\u2014D.10052194"],"award-info":[{"award-number":["23011222\u2014D.10052194"]}],"id":[{"id":"10.13039\/501100005941","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Metabolic testing of cerebrospinal fluid (CSF) is essential for early diagnosis of neurometabolic disorders. However, the large number of differential diagnoses, the phenotypic variance within a clinical picture, and the disease rarity complicate targeted metabolic diagnostics. To improve diagnosis the aim is to establish a liquid chromatography\u2013tandem mass spectrometry (LC\u2013MS\/MS) based CSF panel (NeuroMetabolom) which enables a quick, reliable, extensive and cheap method requiring small amounts of analysis material replacing classical single platform analyses. The novel LC\u2013MS\/MS NeuroMetabolom method enables measuring all known standard metabolites in CSF, including purines\/pyrimidines, sepiapterin, \u03b3\u2010Aminobutyric acid (GABA), and vitamin B\n                    <jats:sub>6<\/jats:sub>\n                    metabolites, with significantly reduced sample volume and measurement time. Due to their different biochemical interactions several runs with different sample preparation, running time and columns are necessary within the LC\u2013MS\/MS. Age\u2010dependent reference values have been established. Positive controls with consistently detectable metabolite patterns were used to assess analytical reliability. The method has been implemented into routine diagnostics practice. The LC\u2013MS\/MS panel enables a simple, comprehensive, and rapid diagnostic approach, reducing time to diagnosis and facilitating early initiation of treatment. Instead of 650\u2009\u03bcL, only 250\u2009\u03bcL CSF is now required and the analysis time for all metabolites is reduced from 280 to 65.3\u2009min excluding preparation and setup time. Furthermore, the panel is adaptable and can be regularly expanded to include additional clinically relevant metabolites. The novel LC\u2013MS\/MS panel, together with a neurometabolomic approach, offers a promising avenue to timely clinical diagnosis.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    German Clinical Trials Register: DRKS00007878\n                  <\/jats:p>","DOI":"10.1002\/jimd.70167","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:05:09Z","timestamp":1775520309000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Novel Multimodal\n                    <scp>LC<\/scp>\n                    \u2013\n                    <scp>MS<\/scp>\n                    \/\n                    <scp>MS<\/scp>\n                    Panel for the Comprehensive Diagnosis of Neurometabolic Disorders in\n                    <scp>CSF<\/scp>"],"prefix":"10.1002","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2092-4716","authenticated-orcid":false,"given":"Stine","family":"Christ","sequence":"first","affiliation":[{"name":"Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine Department I Division of Pediatric Neurology and Metabolic Medicine Heidelberg University  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Rossmann","sequence":"additional","affiliation":[{"name":"Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine Department I Division of Pediatric Neurology and Metabolic Medicine Heidelberg University  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Richter","sequence":"additional","affiliation":[{"name":"Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine Department I Division of Pediatric Neurology and Metabolic Medicine Heidelberg University  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7420-4757","authenticated-orcid":false,"given":"Sven","family":"Garbade","sequence":"additional","affiliation":[{"name":"Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine Department I Division of Pediatric Neurology and Metabolic Medicine Heidelberg University  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glynis","family":"Klinke","sequence":"additional","affiliation":[{"name":"Metabolomics Core Technology Platform, Centre for Organismal Studies (COS) Heidelberg University  Heidelberg Germany"},{"name":"Cellzome GmbH A GSK Company  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nenad","family":"Blau","sequence":"additional","affiliation":[{"name":"Division of Metabolism University Children\u2019s Hospital  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg Friedrich","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine Department I Division of Pediatric Neurology and Metabolic Medicine Heidelberg University  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen G\u00fcnther","family":"Okun","sequence":"additional","affiliation":[{"name":"Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine Department I Division of Pediatric Neurology and Metabolic Medicine Heidelberg University  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4349-7662","authenticated-orcid":false,"given":"Thomas","family":"Opladen","sequence":"additional","affiliation":[{"name":"Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine Department I Division of Pediatric Neurology and Metabolic Medicine Heidelberg University  Heidelberg Germany"},{"name":"MetabERN Subnetwork for Neurotransmitters and Other Small Molecules  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,6]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0966-5"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2023.109338"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-018-0146-7"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2014.01.019"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12060"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-016-9972-7"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo12050373"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.3109\/10408363.2013.847896"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-022-04588-4"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2018.11.05"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12213"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1258\/acb.2008.008029"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/38.12.2405"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2022.123503"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1996.tb02095.x"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-540-76698-8_6"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/hvae139"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12649"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-540-76698-8_28"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2011.05.014"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17745"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.3109\/00365513.2013.803234"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2024.120111"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12244"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI148272"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2023.11.013"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-009-1094-z"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0212458"},{"issue":"2","key":"e_1_2_14_30_1","first-page":"91","article-title":"Laboratory Diagnosis of Rare Diseases","volume":"31","author":"Artuch Iriberri R.","year":"2008","journal-title":"Anales Del Sistema Sanitario de Navarra"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11916-024-01262-2"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-017-0131-6"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.70167","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jimd.70167","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.70167","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T08:35:20Z","timestamp":1784622920000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jimd.70167"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,6]]},"references-count":31,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/jimd.70167"],"URL":"https:\/\/doi.org\/10.1002\/jimd.70167","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,6]]},"assertion":[{"value":"2025-08-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70167"}}