{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T03:26:19Z","timestamp":1768015579368,"version":"3.49.0"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,4,17]],"date-time":"2019-04-17T00:00:00Z","timestamp":1555459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,4,17]],"date-time":"2019-04-17T00:00:00Z","timestamp":1555459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Current therapies have not shown benefit in organ damage reversal in Fabry disease (FD), but biomarkers could help risk stratification and prognosis. We investigated if several biomarkers of cardiac fibrosis, cardiac wall stress, myocardial injury, renal function and inflammation, are associated with early cardiac affectation in FD patients. We included FD patients from four cardiology outpatient clinics of southeastern Spain. At inclusion, Galectin-3 (Gal-3), N-terminal proB-type natriuretic peptide, high sensitivity troponin T (hsTnT), \u03b2-trace protein (BTP) and interleukin-6 concentrations were measured. The relation of biomarkers concentrations with clinical features, cardiac involvement and organ affectation according to the Mainz Severity Score Index (MSSI) was investigated. 44 FD patients (n\u2009=\u200921 affected and n\u2009=\u200923 unaffected) were compared to age and sex-respectively matched healthy controls. Significant differences in biomarkers\u2019 concentration between FD groups were observed. Importantly, Gal-3 and BTP levels were higher in unaffected patients when compared with age and sex-matched healthy controls (both p\u2009&lt;\u20090.05). All the biomarkers correlated with clinical features. When cut-off values for clinical affectation (measured as MSSI\u2009\u2265\u200920) were established, only hsTnT (OR 30.69, 95% CI 2.70\u2013348.42) and male sex (OR 8.17, 95% CI 1.16\u201357.75) were independently associated with cardiac damage by multivariate regression analysis. Gal-3 and BTP levels are increased in unaffected FD patients compared to healthy controls. This suggests that these biomarkers could be useful for the early detection of cardiac affectation in FD patients. On the other hand, hsTnT and male sex are independent risk factors for established clinical cardiac damage in FD.<\/jats:p>","DOI":"10.1038\/s41598-019-42727-4","type":"journal-article","created":{"date-parts":[[2019,4,17]],"date-time":"2019-04-17T10:14:19Z","timestamp":1555496059000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Galectin-3 and \u03b2-trace protein concentrations are higher in clinically unaffected patients with Fabry disease"],"prefix":"10.1038","volume":"9","author":[{"given":"Diana","family":"Hern\u00e1ndez-Romero","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"S\u00e1nchez-Qui\u00f1ones","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Antonio","family":"V\u00edlchez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0492-6241","authenticated-orcid":false,"given":"Jos\u00e9 Miguel","family":"Rivera-Caravaca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gonzalo","family":"de la Morena","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory Y. H.","family":"Lip","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vicente","family":"Climent","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco","family":"Mar\u00edn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,4,17]]},"reference":[{"key":"42727_CR1","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1007\/s00392-002-0870-7","volume":"91","author":"G Beer","year":"2002","unstructured":"Beer, G., Reinecke, P., Gabbert, H. E., Hort, W. & Kuhn, H. Fabry disease in patients with hypertrophic cardiomyopathy (HCM). Z. Kardiol. 91, 992\u20131002 (2002).","journal-title":"Z. Kardiol."},{"key":"42727_CR2","unstructured":"Scriver, C., Beaudet, A., Sly, W., Valle, D. & Childs, B. The Metabolic and Molecular Bases of Inherited Disease. New York: McGraw Hill (2001)."},{"key":"42727_CR3","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1136\/jmg.38.11.750","volume":"38","author":"KD MacDermot","year":"2001","unstructured":"MacDermot, K. D., Holmes, A. & Miners, A. H. Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 98 hemizygous males. J. Med. Genet. 38, 750\u201360 (2001).","journal-title":"J. Med. Genet."},{"key":"42727_CR4","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1136\/jmg.38.11.769","volume":"38","author":"KD MacDermot","year":"2001","unstructured":"MacDermot, K. D., Holmes, A. & Miners, A. H. Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 60 obligate carrier females. J. Med. Genet. 38, 769\u201375 (2001).","journal-title":"J. Med. Genet."},{"key":"42727_CR5","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1159\/000060196","volume":"136","author":"C Whybra","year":"2001","unstructured":"Whybra, C., Wendrich, K., Ries, M., Gal, A. & Beck, M. Clinical manifestation in female Fabry disease patients. Contrib. Nephrol. 136, 245\u201350 (2001).","journal-title":"Contrib. Nephrol."},{"key":"42727_CR6","doi-asserted-by":"crossref","unstructured":"Doerr, W., Hort, W., Bauernschmitt, R. & Hagl, S. Pathologie des Endokard, der Kranzarterien und des Myokard. Berlin: Springer (2000).","DOI":"10.1007\/978-3-642-56944-9_1"},{"key":"42727_CR7","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1159\/000060188","volume":"136","author":"JP Grunfeld","year":"2001","unstructured":"Grunfeld, J. P., Lidove, O. & Barbey, F. Heterozygotes with Fabry\u2019s disease. Contrib. Nephrol. 136, 208\u201310 (2001).","journal-title":"Contrib. Nephrol."},{"key":"42727_CR8","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1080\/08035320600618825","volume":"95","author":"M Beck","year":"2006","unstructured":"Beck, M. The Mainz Severity Score Index (MSSI): development and validation of a system for scoring the signs and symptoms of Fabry disease. Acta Paediatr. Suppl. 95, 43\u20136 (2006).","journal-title":"Acta Paediatr. Suppl."},{"key":"42727_CR9","doi-asserted-by":"publisher","first-page":"2399","DOI":"10.1016\/j.jacc.2007.06.062","volume":"50","author":"L Monserrat","year":"2007","unstructured":"Monserrat, L. et al. Prevalence of fabry disease in a cohort of 508 unrelated patients with hypertrophic cardiomyopathy. J. Am. Coll. Cardiol. 50, 2399\u2013403 (2007).","journal-title":"J. Am. Coll. Cardiol."},{"key":"42727_CR10","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.beem.2014.10.003","volume":"29","author":"N Seydelmann","year":"2015","unstructured":"Seydelmann, N., Wanner, C., Stork, S., Ertl, G. & Weidemann, F. Fabry disease and the heart. Best Pract. Res. Clin. Endocrinol. Metab. 29, 195\u2013204 (2015).","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"42727_CR11","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1007\/s10545-007-0521-2","volume":"30","author":"CM Eng","year":"2007","unstructured":"Eng, C. M. et al. Fabry disease: baseline medical characteristics of a cohort of 1765 males and females in the Fabry Registry. J. Inherit. Metab. Dis. 30, 184\u201392 (2007).","journal-title":"J. Inherit. Metab. Dis."},{"key":"42727_CR12","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1590\/S1415-47572012000600009","volume":"35","author":"T Alegra","year":"2012","unstructured":"Alegra, T., Vairo, F., de Souza, M. V., Krug, B. C. & Schwartz, I. V. Enzyme replacement therapy for Fabry disease: A systematic review and meta-analysis. Genet. Mol. Biol. 35, 947\u201354 (2012).","journal-title":"Genet. Mol. Biol."},{"key":"42727_CR13","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1093\/eurheartj\/ehn538","volume":"30","author":"F Cambronero","year":"2009","unstructured":"Cambronero, F. et al. Biomarkers of pathophysiology in hypertrophic cardiomyopathy: implications for clinical management and prognosis. Eur. Heart J. 30, 139\u201351 (2009).","journal-title":"Eur. Heart J."},{"key":"42727_CR14","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1161\/CIRCGENETICS.113.000249","volume":"7","author":"M Niemann","year":"2014","unstructured":"Niemann, M. et al. Gene mutations versus clinically relevant phenotypes: lyso-Gb3 defines Fabry disease. Circ. Cardiovasc. Genet. 7, 8\u201316 (2014).","journal-title":"Circ. Cardiovasc. Genet."},{"key":"42727_CR15","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.cca.2017.01.018","volume":"466","author":"C Auray-Blais","year":"2017","unstructured":"Auray-Blais, C. et al. Biomarkers associated with clinical manifestations in Fabry disease patients with a late-onset cardiac variant mutation. Clin. Chim. Acta 466, 185\u201393 (2017).","journal-title":"Clin. Chim. Acta"},{"key":"42727_CR16","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.1039\/c3mb25402j","volume":"9","author":"D Cigna","year":"2013","unstructured":"Cigna, D. et al. Alteration of proteomic profiles in PBMC isolated from patients with Fabry disease: preliminary findings. Mol. Biosyst. 9, 1162\u20138 (2013).","journal-title":"Mol. Biosyst."},{"key":"42727_CR17","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1007\/s10545-012-9547-1","volume":"36","author":"YH Chien","year":"2013","unstructured":"Chien, Y. H. et al. Lyso-globotriaosylsphingosine (lyso-Gb3) levels in neonates and adults with the Fabry disease later-onset GLA IVS4\u2009+\u2009919G\u2009>\u2009A mutation. J. Inherit. Metab. Dis. 36, 881\u20135 (2013).","journal-title":"J. Inherit. Metab. Dis."},{"key":"42727_CR18","doi-asserted-by":"publisher","first-page":"e0157640","DOI":"10.1371\/journal.pone.0157640","volume":"11","author":"C Tanislav","year":"2016","unstructured":"Tanislav, C. et al. Cardiac Troponin I: A Valuable Biomarker Indicating the Cardiac Involvement in Fabry Disease. PLoS One 11, e0157640 (2016).","journal-title":"PLoS One"},{"key":"42727_CR19","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.amjcard.2012.08.055","volume":"111","author":"CJ Coats","year":"2013","unstructured":"Coats, C. J. et al. Role of serum N-terminal pro-brain natriuretic peptide measurement in diagnosis of cardiac involvement in patients with anderson-fabry disease. Am. J. Cardiol. 111, 111\u20137 (2013).","journal-title":"Am. J. Cardiol."},{"key":"42727_CR20","doi-asserted-by":"publisher","first-page":"1221.e1","DOI":"10.1016\/j.cjca.2015.10.033","volume":"32","author":"KH Chen","year":"2016","unstructured":"Chen, K. H. et al. Evaluation of Proinflammatory Prognostic Biomarkers for Fabry Cardiomyopathy With Enzyme Replacement Therapy. Can. J. Cardiol. 32, 1221.e1\u201321.e9 (2016).","journal-title":"Can. J. Cardiol."},{"key":"42727_CR21","doi-asserted-by":"publisher","DOI":"10.1038\/srep40378","volume":"7","author":"D Hernandez-Romero","year":"2017","unstructured":"Hernandez-Romero, D. et al. Galectin-3 as a marker of interstitial atrial remodelling involved in atrial fibrillation. Sci. Rep. 7, 40378 (2017).","journal-title":"Sci. Rep."},{"key":"42727_CR22","doi-asserted-by":"publisher","first-page":"S42","DOI":"10.1016\/j.ymgme.2014.12.079","volume":"114","author":"P Ergun","year":"2015","unstructured":"Ergun, P. et al. Can cathepsin-D and galectin-3 be new inflammation biomarkers in detection of lysosomal diseases? Mol. Gen. Met. 114, S42 (2015).","journal-title":"Mol. Gen. Met."},{"key":"42727_CR23","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1016\/j.cardfail.2010.07.245","volume":"16","author":"V Moreno","year":"2010","unstructured":"Moreno, V. et al. Serum levels of high-sensitivity troponin T: a novel marker for cardiac remodeling in hypertrophic cardiomyopathy. J. Card. Fail. 16, 950\u20136 (2010).","journal-title":"J. Card. Fail."},{"key":"42727_CR24","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/1471-2261-11-6","volume":"11","author":"C Tanislav","year":"2011","unstructured":"Tanislav, C. et al. Persistent increase in cardiac troponin I in Fabry disease: a case report. BMC Cardiovasc. Disord. 11, 6 (2011).","journal-title":"BMC Cardiovasc. Disord."},{"key":"42727_CR25","doi-asserted-by":"publisher","first-page":"e002839","DOI":"10.1161\/JAHA.115.002839","volume":"5","author":"N Seydelmann","year":"2016","unstructured":"Seydelmann, N. et al. High-Sensitivity Troponin: A Clinical Blood Biomarker for Staging Cardiomyopathy in Fabry Disease. J. Am. Heart Assoc. 5, e002839, https:\/\/doi.org\/10.1161\/JAHA.115.002839 (2016).","journal-title":"J. Am. Heart Assoc."},{"key":"42727_CR26","doi-asserted-by":"publisher","first-page":"108","DOI":"10.3389\/fcvm.2018.00108","volume":"5","author":"J Loso","year":"2018","unstructured":"Loso, J. et al. Serum Biomarkers of Endothelial Dysfunction in Fabry Associated Cardiomyopathy. Front. Cardiovasc. Med. 5, 108 (2018).","journal-title":"Front. Cardiovasc. Med."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-42727-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-42727-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-42727-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T08:54:15Z","timestamp":1671267255000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-42727-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,17]]},"references-count":26,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["42727"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-42727-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,17]]},"assertion":[{"value":"1 October 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 April 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 April 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"6235"}}