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In recent years, novel therapies have shown to improve clinical outcomes. Yet, the absence of reliable biomarkers renders clinical assessment and prognosis of possibly already affected newborns with a positive newborn screening result for SMA imprecise and difficult. Therapeutic decisions and stratification of individualized therapies remain challenging, especially in symptomatic children. The aim of this proof-of-concept and feasibility study was to explore the value of <jats:sup>1<\/jats:sup>H-nuclear magnetic resonance (NMR)-based metabolic profiling in identifying non-invasive diagnostic and prognostic urinary fingerprints in children and adolescents with SMA.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Urine samples were collected from 29 treatment-na\u00efve SMA patients (5 pre-symptomatic, 9 SMA 1, 8 SMA 2, 7 SMA 3), 18 patients with Duchenne muscular dystrophy (DMD) and 444 healthy controls. Using machine-learning algorithms, we propose a set of prediction models built on urinary fingerprints that showed potential diagnostic value in discriminating SMA patients from controls and DMD, as well as predictive properties in separating between SMA types, allowing predictions about phenotypic severity. Interestingly, preliminary results of the prediction models suggest additional value in determining biochemical onset of disease in pre-symptomatic infants with SMA identified by genetic newborn screening and furthermore as potential therapeutic monitoring tool.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>This study provides preliminary evidence for the use of <jats:sup>1<\/jats:sup>H-NMR-based urinary metabolic profiling as diagnostic and prognostic biomarker in spinal muscular atrophy.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13023-021-02075-x","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T11:31:08Z","timestamp":1634729468000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["1H-NMR-based metabolic profiling identifies non-invasive diagnostic and predictive urinary fingerprints in 5q spinal muscular atrophy"],"prefix":"10.1186","volume":"16","author":[{"given":"Afshin","family":"Saffari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Cannet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Blaschek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Hahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg F.","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessika","family":"Johannsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romy","family":"Kirsten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Musa","family":"Kockaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"K\u00f6lker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"M\u00fcller-Felber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Roos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hartmut","family":"Sch\u00e4fer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Schara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Spraul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedrich K.","family":"Trefz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Vill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Wick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Weiler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen G.","family":"Okun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7574-1231","authenticated-orcid":false,"given":"Andreas","family":"Ziegler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,20]]},"reference":[{"issue":"9630","key":"2075_CR1","doi-asserted-by":"crossref","first-page":"2120","DOI":"10.1016\/S0140-6736(08)60921-6","volume":"371","author":"MR Lunn","year":"2008","unstructured":"Lunn MR, Wang CH. 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J Proteome Res. 2009;8(9):4264\u201371.","journal-title":"J Proteome Res"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-021-02075-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-021-02075-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-021-02075-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T08:24:25Z","timestamp":1635236665000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-021-02075-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,20]]},"references-count":46,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["2075"],"URL":"https:\/\/doi.org\/10.1186\/s13023-021-02075-x","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,20]]},"assertion":[{"value":"26 July 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 October 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 October 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The clinical protocol was approved by the ethics committees of the Universities of Heidelberg (S-554\/2018), Hamburg (MC-265\/19) and Munich (18-269) for sample collection of SMA and DMD patients, and the ethics committee of the State Medical Council of Baden W\u00fcrttemberg for sample collection of healthy controls (F-2013-006#A). All patients and their legal guardians enrolled in this study provided signed informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Afshin Saffari received partial funding for the study through a Sponsor Research Agreement with Biogen Inc. He received travel grants from Biogen Inc., which manufactures therapies for SMA. Claire Cannet has nothing to report. Astrid Blaschek has nothing to report. Andreas Hahn has nothing to report. Georg F. Hoffmann received a grant for the establishment of prediction models for screened newborns with SMA from the Dietmar Hopp Foundation, St. Leon-Rot, Germany. Jessika Johannsen received advisory board and\/or speaker honoraria and financial support for conference attendances from Avexis, Biogen, Roche, PTC and Sarepta. Romy Kirsten has nothing to report. Musa Kockaya has nothing to report. Stefan K\u00f6lker received a grant for the establishment of prediction models for screened newborns with SMA from the Dietmar Hopp Foundation, St. Leon-Rot, Germany. Wolfgang M\u00fcller-Felber reports personal fees from Avexis (Advisory baord, Talks), personal fees from Biogen (Advisory baord, Talks), personal fees from PTC (Advisory baord, Talks), personal fees from Sarepta (Advisory baord, Talks), personal fees from Roche (Advisory board) and personal fees from Sanofi-Aventis (Advisory baord, Talks). Andreas Roos has nothing to report. Hartmut Sch\u00e4fer has nothing to report. Ulrike Schara received advisory board and\/or speaker honoraria from Avexis, Biogen, Roche, PTC, Santhera, Sarepta, Pfizer, Alexion and Sanofi. Manfred Spraul has nothing to report. Friedrich K. Trefz has nothing to report. Katharina Vill has nothing to report. Wolfgang Wick has nothing to report. Markus Weiler received advisory board and\/or speaker honoraria and financial support for conference attendances from Akcea Therapeutics, Alnylam Pharmaceuticals, Biogen, and Pfizer, and advisory board and consultant honoraria from Hoffmann-La Roche. J\u00fcrgen G. Okun has nothing to report. Andreas Ziegler received partial funding for the study through a Sponsor Research Agreement with Biogen Inc. He received advisory board and\/or speaker honoraria and financial support for conference attendances from Avexis, Biogen, Roche, PTC, and Santhera.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"441"}}