{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T00:23:24Z","timestamp":1792887804038,"version":"4.5.0"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,12,25]],"date-time":"2024-12-25T00:00:00Z","timestamp":1735084800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,12,25]],"date-time":"2024-12-25T00:00:00Z","timestamp":1735084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271478"],"award-info":[{"award-number":["82271478"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82001218"],"award-info":[{"award-number":["82001218"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by proximal muscle weakness and atrophy. The increasing availability of disease-modifying therapies has prompted the development of biomarkers to facilitate clinical assessments. We explored the association between disease severity and serum creatinine (Crn) levels in SMA patients undergoing up to two years of treatment with nusinersen.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We measured serum Crn levels and assessed function performance using the Hammersmith Functional Motor Scale-Expanded (HFMSE), Medical Research Council Scale (MRC), 6-Minute Walk Test (6MWT), ulnar Compound Muscle Action Potential (CMAP), and forced vital capacity (FVC) in a cohort comprising 28 adolescent and adult patients with SMA. The association between Crn and disease severity was investigated through partial rank correlation analysis and linear mixed models while accounting for age, gender, and BMI. Linear models were employed to predict functional performance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      28 SMA patients and 28 gender- and age-matched healthy controls (HCs) were included, resulting in a dataset of 185 visits. Compared to HCs, SMA patients exhibited significantly lower Crn values \u200b\u200b(67.4\u2009\u00b1\u200914 vs. 23.7\u2009\u00b1\u200914.8 umol\/L,\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.0001). After adjusting for age, sex, and BMI, Crn showed positive correlations with the HFMSE (\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.0001,\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.884), MRC (\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.0001,\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.827), FVC (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002,\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.730), and ulnar CMAP (\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.0001,\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.807). Patients with SMN2 copy number\u2009\u2265\u20094 had nearly twice as high Crn levels as those with SMN2 copy number\u2009&lt;\u20094 (34.1\u2009\u00b1\u20093.75 vs. 17.2\u2009\u00b1\u20092.52 umol\/L,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.00145). Ambulant SMA patients had more than double the Crn levels compared to non-ambulant ones (32\u2009\u00b1\u20092.33 vs. 12.9\u2009\u00b1\u20092.38 umol\/L,\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.0001). Furthermore, Crn explained that up to 83.5% of the variance in functional performance measured by HFMSE, MRC, and 6MWT was significantly higher than that of traditional biomarkers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings suggest that Crn may be a potential biomarker for assessing disease severity in adolescents and adults with SMA, demonstrating its promise in clinical applications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-024-03515-0","type":"journal-article","created":{"date-parts":[[2024,12,25]],"date-time":"2024-12-25T08:35:59Z","timestamp":1735115759000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A cross-sectional and longitudinal evaluation of serum creatinine as a biomarker in spinal muscular atrophy"],"prefix":"10.1186","volume":"19","author":[{"given":"Xin","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenxiang","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zehui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangqin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhua","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirui","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Ba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3752-9808","authenticated-orcid":false,"given":"Min","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,25]]},"reference":[{"issue":"8710","key":"3515_CR1","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/0140-6736(90)91803-I","volume":"336","author":"J Melki","year":"1990","unstructured":"Melki J, et al. Mapping of acute (type I) spinal muscular atrophy to chromosome 5q12-q14. The French spinal muscular atrophy investigators. Lancet. 1990;336(8710):271\u20133.","journal-title":"Lancet"},{"issue":"1","key":"3515_CR2","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1038\/s41572-022-00380-8","volume":"8","author":"E Mercuri","year":"2022","unstructured":"Mercuri E, et al. Spinal muscular atrophy. Nat Rev Dis Primers. 2022;8(1):52.","journal-title":"Nat Rev Dis Primers"},{"issue":"14","key":"3515_CR3","doi-asserted-by":"publisher","first-page":"e1527","DOI":"10.1212\/WNL.0000000000200986","volume":"99","author":"BH Lee","year":"2022","unstructured":"Lee BH, et al. Newborn screening for spinal muscular atrophy in New York State: clinical outcomes from the first 3 years. 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J Neurol Neurosurg Psychiatry. 2020;91(11):1166\u201374.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"5","key":"3515_CR10","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1002\/ana.20473","volume":"57","author":"KJ Swoboda","year":"2005","unstructured":"Swoboda KJ, et al. Natural history of denervation in SMA: relation to age, SMN2 copy number, and function. Ann Neurol. 2005;57(5):704\u201312.","journal-title":"Ann Neurol"},{"issue":"1","key":"3515_CR11","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1007\/s00415-019-09547-y","volume":"267","author":"CD Wurster","year":"2020","unstructured":"Wurster CD, et al. Neurofilament light chain in serum of adolescent and adult SMA patients under treatment with nusinersen. 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Metabolic and Nutritional issues Associated with spinal muscular atrophy. Nutrients, 2020. 12(12).","DOI":"10.3390\/nu12123842"},{"issue":"3","key":"3515_CR21","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1152\/physrev.2000.80.3.1107","volume":"80","author":"M Wyss","year":"2000","unstructured":"Wyss M, Kaddurah-Daouk R. Creatine and creatinine metabolism. Physiol Rev. 2000;80(3):1107\u2013213.","journal-title":"Physiol Rev"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-024-03515-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-024-03515-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-024-03515-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,25]],"date-time":"2024-12-25T09:02:24Z","timestamp":1735117344000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-024-03515-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,25]]},"references-count":21,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["3515"],"URL":"https:\/\/doi.org\/10.1186\/s13023-024-03515-0","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-4467679\/v1","asserted-by":"object"}]},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,25]]},"assertion":[{"value":"24 May 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 December 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 December 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the institutional review boards of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, adhering to the principles outlined in the Declaration of Helsinki (2022-S184). Written informed consent was taken from the participating patients\u2019 legal guardians.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent was obtained to publish genetic data and clinical information from the participating patients\u2019 legal guardians.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"489"}}