{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T04:40:48Z","timestamp":1760762448773,"version":"build-2065373602"},"reference-count":28,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004339","name":"Sanofi","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomedicines"],"abstract":"<jats:p>Background\/Objectives: Fabry disease (FD) is a rare X-linked disease caused by the deficient activity of the enzyme \u03b1-galactosidase A. Cardiac involvement is particularly critical, often determining the disease prognosis. Epidemiological data on FD in Portugal are limited and inconsistent, highlighting the need for targeted screening. The F-CHECK study aimed to determine the prevalence of FD through the systematic screening of a Portuguese cohort of patients with unexplained cardiomyopathies. Methods: This multicenter observational study (NCT05409846) assessed the prevalence and clinical characteristics of FD in a Portuguese cohort (n = 409) of patients from 10 central hospitals who presented with unexplained cardiomyopathies, including idiopathic hypertrophic cardiomyopathy (HCM), left ventricular hypertrophy, dilated-phase HCM, and dilated cardiomyopathy with late gadolinium enhancement in the inferolateral segment. Screening was performed using dried blood spot assays to measure \u03b1-galactosidase A activity and\/or by GLA gene sequencing in whole-blood samples. Results: FD was diagnosed in 14 patients, corresponding to a prevalence of 3.4%. FD diagnosis was significantly associated with systemic manifestations such as acroparesthesias (p = 0.027) and angiokeratomas (p = 0.003), as well as an increased risk of prior arrhythmic events (p = 0.021) and cerebrovascular disease (p = 0.016). Most FD patients (57%) presented a non-founder mutation in the GLA gene; however, they were pathogenically relevant. Conclusions: The observed 3.4% prevalence highlights the importance of systematic FD screening among Portuguese patients with unexplained cardiomyopathy, extending beyond classic hypertrophic presentations to dilated forms. Specific clinical signs, electrocardiogram findings, and cardiac imaging features can serve as valuable indicators to guide targeted genetic testing for FD.<\/jats:p>","DOI":"10.3390\/biomedicines13102530","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T16:33:22Z","timestamp":1760632402000},"page":"2530","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fabry Disease Screening in Patients with Idiopathic HCM or LVH: Data from the Multicentric Nationwide F-CHECK Study"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3708-4529","authenticated-orcid":false,"given":"Raquel","family":"Machado","sequence":"first","affiliation":[{"name":"Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7010-2104","authenticated-orcid":false,"given":"In\u00eas","family":"Fortuna","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]},{"given":"S\u00edlvia","family":"Sousa","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]},{"given":"Catarina","family":"Costa","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o, European Reference Network for Rare, Low-Prevalence, or Complex Diseases of the Heart (ERN GUARD-Heart), 4200-219 Porto, Portugal"}]},{"given":"Jo\u00e3o","family":"Calv\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o, European Reference Network for Rare, Low-Prevalence, or Complex Diseases of the Heart (ERN GUARD-Heart), 4200-219 Porto, Portugal"}]},{"given":"Ana Filipa","family":"Amador","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o, European Reference Network for Rare, Low-Prevalence, or Complex Diseases of the Heart (ERN GUARD-Heart), 4200-219 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2147-5913","authenticated-orcid":false,"given":"Patr\u00edcia","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Centro Hospitalar Universit\u00e1rio do Porto, 4050-342 Porto, Portugal"},{"name":"Unit for Multidisciplinary Research in Biomedicine, Institute for the Biomedical Sciences Abel Salazar, University of Porto, 4050-313 Porto, Portugal"}]},{"given":"Dulce","family":"Brito","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Universit\u00e1rio de Santa Maria, 1649-028 Lisboa, Portugal"},{"name":"CCUL@RISE, Faculty of Medicine, University of Lisbon, 1649-028 Lisboa, Portugal"}]},{"given":"Marta","family":"Vilela","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Universit\u00e1rio de Santa Maria, 1649-028 Lisboa, Portugal"},{"name":"CCUL@RISE, Faculty of Medicine, University of Lisbon, 1649-028 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3103-4353","authenticated-orcid":false,"given":"Nat\u00e1lia","family":"Ant\u00f3nio","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Centro Hospitalar e Universit\u00e1rrio de Coimbra, 3004-561 Coimbra, Portugal"},{"name":"Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"given":"Vanessa","family":"Lopes","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Centro Hospitalar e Universit\u00e1rrio de Coimbra, 3004-561 Coimbra, Portugal"}]},{"given":"Cristina","family":"Gavina","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"Department of Cardiology, ULS Matosinhos, 4464-513 Matosinhos, Portugal"}]},{"given":"Ana Sofia","family":"Correia","sequence":"additional","affiliation":[{"name":"Department of Cardiology, ULS Matosinhos, 4464-513 Matosinhos, Portugal"}]},{"given":"Concei\u00e7\u00e3o","family":"Queir\u00f3s","sequence":"additional","affiliation":[{"name":"Department of Cardiology, ULS T\u00e2mega e Sousa, 4564-007 Penafiel, Portugal"}]},{"given":"Alexandra","family":"Toste","sequence":"additional","affiliation":[{"name":"Hospital da Luz, 1500-650 Lisboa, Portugal"}]},{"given":"Alexandra","family":"Sousa","sequence":"additional","affiliation":[{"name":"Department of Cardiology, ULS Entre Douro e Vouga, 4520-211 Santa Maria da Feira, Portugal"}]},{"given":"Ricardo","family":"Fontes-Carvalho","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"Department of Cardiology, ULS Gaia e Espinho, 4434-502 Vila Nova de Gaia, Portugal"}]},{"given":"Andr\u00e9","family":"Lobo","sequence":"additional","affiliation":[{"name":"Department of Cardiology, ULS Gaia e Espinho, 4434-502 Vila Nova de Gaia, Portugal"}]},{"given":"In\u00eas","family":"Silveira","sequence":"additional","affiliation":[{"name":"Department of Cardiology, ULS Tr\u00e1s-os-Montes e Alto Douro, 5000-508 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8388-1848","authenticated-orcid":false,"given":"Janete","family":"Quelhas-Santos","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6944-2953","authenticated-orcid":false,"given":"Elisabete","family":"Martins","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"Department of Cardiology, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o, European Reference Network for Rare, Low-Prevalence, or Complex Diseases of the Heart (ERN GUARD-Heart), 4200-219 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ymgme.2022.07.010","article-title":"An expert consensus on practical clinical recommendations and guidance for patients with classic Fabry disease","volume":"137","author":"Germain","year":"2022","journal-title":"Mol. Genet. Metab."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Azevedo, O., Cordeiro, F., Gago, M.F., Miltenberger-Miltenyi, G., Ferreira, C., Sousa, N., and Cunha, D. (2021). Fabry Disease and the Heart: A Comprehensive Review. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094434"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1093\/eurheartj\/ehae148","article-title":"Anderson-Fabry disease management: Role of the cardiologist","volume":"45","author":"Pieroni","year":"2024","journal-title":"Eur. Heart J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"107585","DOI":"10.1016\/j.ymgme.2023.107585","article-title":"An expert consensus on the recommendations for the use of biomarkers in Fabry disease","volume":"139","author":"Burlina","year":"2023","journal-title":"Mol. Genet. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Simonetta, I., Tuttolomondo, A., Daidone, M., and Pinto, A. (2020). Biomarkers in Anderson\u2013Fabry Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218080"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.ymgme.2020.04.006","article-title":"A comprehensive testing algorithm for the diagnosis of Fabry disease in males and females","volume":"130","author":"Stiles","year":"2020","journal-title":"Mol. Genet. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/sj.ejhg.5201044","article-title":"Prevalence of lysosomal storage diseases in Portugal","volume":"12","author":"Pinto","year":"2004","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.ahj.2020.04.006","article-title":"Predictors of Fabry disease in patients with hypertrophic cardiomyopathy: How to guide the diagnostic strategy?","volume":"226","author":"Azevedo","year":"2020","journal-title":"Am. Heart J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.repc.2017.08.005","article-title":"The Portuguese Registry of Hypertrophic Cardiomyopathy: Overall results","volume":"37","author":"Cardim","year":"2018","journal-title":"Rev. Port. Cardiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.1016\/j.jacc.2007.06.062","article-title":"Prevalence of fabry disease in a cohort of 508 unrelated patients with hypertrophic cardiomyopathy","volume":"50","author":"Monserrat","year":"2007","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1093\/eurjhf\/hfq073","article-title":"Fabry disease mimicking hypertrophic cardiomyopathy: Genetic screening needed for establishing the diagnosis in women","volume":"12","author":"Havndrup","year":"2010","journal-title":"Eur. J. Heart Fail."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1136\/heartjnl-2011-300364","article-title":"Prevalence of Anderson-Fabry disease in patients with hypertrophic cardiomyopathy: The European Anderson-Fabry Disease survey","volume":"97","author":"Elliott","year":"2011","journal-title":"Heart"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1136\/hrt.2010.200188","article-title":"Screening patients with hypertrophic cardiomyopathy for Fabry disease using a filter-paper test: The FOCUS study","volume":"97","author":"Caudron","year":"2011","journal-title":"Heart"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.1016\/j.ijcard.2012.06.069","article-title":"Prevalence of Fabry disease in a predominantly hypertensive population with left ventricular hypertrophy","volume":"167","author":"Terryn","year":"2013","journal-title":"Int. J. Cardiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1016\/j.ijcard.2012.10.076","article-title":"Screening for Fabry disease in patients with left ventricular hypertrophy","volume":"167","author":"Mawatari","year":"2013","journal-title":"Int. J. Cardiol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Citro, R., Prota, C., Ferraioli, D., Iuliano, G., Bellino, M., Radano, I., Silverio, A., Migliarino, S., Polito, M.V., and Ruggiero, A. (2022). Importance of Echocardiography and Clinical \u201cRed Flags\u201d in Guiding Genetic Screening for Fabry Disease. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.838200"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4160","DOI":"10.1002\/ehf2.14135","article-title":"Nationwide screening of Fabry disease in patients with hypertrophic cardiomyopathy in Czech Republic","volume":"9","year":"2022","journal-title":"ESC Heart Fail."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Leung, S.P.Y., Dougherty, S., Zhang, X.Y., Kam, K.K.H., Chi, W.K., Chan, J.Y.S., Fung, E., Wong, J.K.T., Choi, P.C.L., and Chan, D.K.H. (2024). The Asian Fabry Cardiomyopathy High-Risk Screening Study 2 (ASIAN-FAME-2): Prevalence of Fabry Disease in Patients with Left Ventricular Hypertrophy. J. Clin. Med., 13.","DOI":"10.3390\/jcm13133896"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3503","DOI":"10.1093\/eurheartj\/ehad194","article-title":"2023 ESC Guidelines for the management of cardiomyopathies: Developed by the task force on the management of cardiomyopathies of the European Society of Cardiology (ESC)","volume":"44","author":"Arbelo","year":"2023","journal-title":"Eur. Heart J."},{"key":"ref_20","unstructured":"(2022). Medical Laboratories Requirements for Quality and Competence (Standard No. ISO 15189:2022)."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Sadasivan, C., Chow, J.T.Y., Sheng, B., Chan, D.K.H., Fan, Y., Choi, P.C.L., Wong, J.K.T., Tong, M.M.B., Chan, T.-N., and Fung, E. (2020). Screening for Fabry Disease in patients with unexplained left ventricular hypertrophy. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0239675"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4381","DOI":"10.1002\/ehf2.15065","article-title":"Screening for Fabry disease in patients with left ventricular hypertrophy in China: A multicentre and prospective study","volume":"11","author":"Lin","year":"2024","journal-title":"ESC Heart Fail."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2888","DOI":"10.1007\/s00330-024-11203-7","article-title":"Screening for Fabry disease in patients with hypertrophic cardiomyopathy using cardiac magnetic resonance imaging","volume":"35","author":"Li","year":"2024","journal-title":"Eur. Radiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e004252","DOI":"10.1161\/CIRCGEN.123.004252","article-title":"Impact of GLA Variant Classification on the Estimated Prevalence of Fabry Disease: A Systematic Review and Meta-Analysis of Screening Studies","volume":"16","author":"Monda","year":"2023","journal-title":"Circ. Genom. Precis. Med."},{"key":"ref_25","first-page":"e14100","article-title":"Fabry Disease p.M290I Mutation is Related to Organ Involvement: A Case Report","volume":"13","author":"Silva","year":"2021","journal-title":"Cureus"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1161\/STROKEAHA.109.570499","article-title":"Mutations of the GLA Gene in Young Patients with Stroke","volume":"41","author":"Baptista","year":"2010","journal-title":"Stroke"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"131357","DOI":"10.1016\/j.ijcard.2023.131357","article-title":"Left atrial remodeling in hypertrophic cardiomyopathy and Fabry disease: A CMR-based head-to-head comparison and outcome analysis","volume":"393","author":"Moroni","year":"2023","journal-title":"Int. J. Cardiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e037502","DOI":"10.1161\/JAHA.124.037502","article-title":"Characterizing Heart Failure Across the Spectrum of the Preserved Ejection Fraction: Does Heart Failure with Supranormal Ejection Fraction Exist? Data from the Swedish Heart Failure Registry","volume":"14","author":"Landucci","year":"2025","journal-title":"J. Am. Heart Assoc."}],"container-title":["Biomedicines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9059\/13\/10\/2530\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T04:18:04Z","timestamp":1760761084000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9059\/13\/10\/2530"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,16]]},"references-count":28,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["biomedicines13102530"],"URL":"https:\/\/doi.org\/10.3390\/biomedicines13102530","relation":{},"ISSN":["2227-9059"],"issn-type":[{"type":"electronic","value":"2227-9059"}],"subject":[],"published":{"date-parts":[[2025,10,16]]}}}