{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T09:13:06Z","timestamp":1792919586772,"version":"4.5.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e4tsklinikum M\u00fcnster"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Fabry disease is an X-linked lysosomal storage disorder that causes accumulation of glycosphingolipids in body tissues and fluids, leading to progressive organ damage and life-threatening complications. It can affect both males and females and can be classified into classic or later-onset phenotypes. The disease severity in females ranges from asymptomatic to the more severe, classic phenotype. Most females are hemizygous and the X-linked inheritance is associated with variable X-activation pattern and residual enzymatic activity. The heterogeneity of clinical presentation in females requires different approaches to diagnosis and management than males. A European group of 7 physicians, experienced in the management of Fabry disease, convened to discuss patient perspectives and published guidelines. The experts discussed the need to focus on psychological treatment in relation to individual coping styles when monitoring targets, and the lack of data supporting the use of plasma globotriaosylsphingosine over enzyme activity in the diagnosis of these patients. It was suggested that the high phenotypic variability in female patients may be related to the dynamic nature of the X-chromosome inactivation process and further understanding of this process could help predict the progression of Fabry disease in females and facilitate timely intervention. Due to the range of disease severity they exhibit, female patients with Fabry disease may require a more individualized treatment approach than males. Despite current recommendations, the experts agreed that early disease-specific treatment initiation in high-risk females could improve clinical outcome.<\/jats:p>","DOI":"10.1186\/s13023-024-03500-7","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T13:32:00Z","timestamp":1736256720000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Clinical management of female patients with Fabry disease based on expert consensus"],"prefix":"10.1186","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3243-5508","authenticated-orcid":false,"given":"Eva","family":"Brand","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ale\u0161","family":"Linhart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Deegan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruxandra","family":"Jurcut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Pisani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roser","family":"Torra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulla","family":"Feldt-Rasmussen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,7]]},"reference":[{"key":"3500_CR1","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/1750-1172-5-30","volume":"5","author":"DP Germain","year":"2010","unstructured":"Germain DP. Fabry disease. Orphanet J Rare Dis. 2010;5:30.","journal-title":"Orphanet J Rare Dis"},{"key":"3500_CR2","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1016\/j.ymgme.2018.02.014","volume":"123","author":"A Ortiz","year":"2018","unstructured":"Ortiz A, Germain DP, Desnick RJ, Politei J, Mauer M, Burlina A, et al. Fabry disease revisited: Management and treatment recommendations for adult patients. Mol Genet Metab. 2018;123:416\u201327.","journal-title":"Mol Genet Metab"},{"key":"3500_CR3","doi-asserted-by":"publisher","DOI":"10.2478\/rjim-2024-0027","author":"A Murs\u0103","year":"2024","unstructured":"Murs\u0103 A, Militaru S, Rusu E, Onciul S, Neculae G, Adam R, et al. Fabry disease phenotyping in women from the complete Romanian cohort \u2013 time for early diagnostic awareness. Rom J Intern Med. 2024. https:\/\/doi.org\/10.2478\/rjim-2024-0027. [Online ahead of print].","journal-title":"Rom J Intern Med"},{"key":"3500_CR4","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/j.gene.2017.10.064","volume":"641","author":"P Juchniewicz","year":"2018","unstructured":"Juchniewicz P, Kloska A, Tylki-Szyma\u0144ska A, Jak\u00f3bkiewicz-Banecka J, W\u0119grzyn G, Moskot M, et al. Female Fabry disease patients and X-chromosome inactivation. Gene. 2018;641:259\u201364.","journal-title":"Gene"},{"issue":"1","key":"3500_CR5","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1097\/GIM.0b013e31802d8321","volume":"9","author":"RY Wang","year":"2007","unstructured":"Wang RY, Lelis A, Mirocha J, Wilcox WR. Heterozygous Fabry women are not just carriers, but have a significant burden of disease and impaired quality of life. Genet Med. 2007;9(1):34\u201345.","journal-title":"Genet Med"},{"key":"3500_CR6","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s13148-021-01019-3","volume":"13","author":"T Di Risi","year":"2021","unstructured":"Di Risi T, Vinciguerra R, Cuomo M, Della Monica R, Riccio E, Cocozza S, et al. DNA methylation impact on Fabry disease. Clin Epigenetics. 2021;13:24.","journal-title":"Clin Epigenetics"},{"key":"3500_CR7","doi-asserted-by":"publisher","first-page":"1979","DOI":"10.1002\/ajmg.a.62728","volume":"188","author":"M \u0158eboun","year":"2022","unstructured":"\u0158eboun M, Sikora J, Magner M, Wiederlechnerov\u00e1 H, \u010cern\u00e1 A, Poup\u011btov\u00e1 H, et al. Pitfalls of X-chromosome inactivation testing in females with Fabry disease. Am J Med Genet A. 2022;188:1979\u201389.","journal-title":"Am J Med Genet A"},{"key":"3500_CR8","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1111\/cge.12613","volume":"89","author":"L Echevarria","year":"2016","unstructured":"Echevarria L, Benistan K, Toussaint A, Dubourg O, Hagege AA, Eladari D, et al. X-chromosome inactivation in female patients with Fabry disease. Clin Genet. 2016;89:44\u201354.","journal-title":"Clin Genet"},{"key":"3500_CR9","unstructured":"EMA. SMPC Galafold. https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/galafold-epar-product-information_en.pdf. Accessed 16 November 2023."},{"key":"3500_CR10","unstructured":"Amicus. Galafold. https:\/\/www.galafoldamenabilitytable.com\/hcp Accessed 16 November 2023."},{"key":"3500_CR11","unstructured":"EMA. Elfabrio. https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/elfabrio Accessed 16 November 2023."},{"key":"3500_CR12","unstructured":"FDA. Elfabrio. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2023\/761161s000lbl.pdf Accessed 16 November 2023."},{"key":"3500_CR13","doi-asserted-by":"crossref","unstructured":"Biegstraaten M, Arngr\u00edmsson R, Barbey F, Boks L, Cecchi F, Deegan PB, et al. Recommendations for initiation and cessation of enzyme replacement therapy in patients with Fabry disease: the European Fabry Working Group consensus document. Orphanet J Rare Dis. 2015;10:36.","DOI":"10.1186\/s13023-015-0253-6"},{"key":"3500_CR14","doi-asserted-by":"publisher","first-page":"551","DOI":"10.2147\/TCRM.S247814","volume":"16","author":"I Vardarli","year":"2020","unstructured":"Vardarli I, Rischpler C, Herrmann K, Weidemann F. Diagnosis and Screening of Patients with Fabry Disease. Ther Clin Risk Manag. 2020;16:551\u20138.","journal-title":"Ther Clin Risk Manag"},{"key":"3500_CR15","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1111\/cge.14102","volume":"101","author":"DP Germain","year":"2022","unstructured":"Germain DP, Levade T, Hachulla E, Knebelmann B, Lacombe D, Leguy Seguin V, et al. Challenging the traditional approach for interpreting genetic variants: Lessons from Fabry disease. Clin Genet. 2022;101:390\u2013402.","journal-title":"Clin Genet"},{"key":"3500_CR16","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.ymgme.2017.07.002","volume":"123","author":"A Nowak","year":"2018","unstructured":"Nowak A, Mechtler TP, Hornemann T, Gawinecka J, Theswet E, Hilz MJ, et al. Genotype, phenotype and disease severity reflected by serum LysoGb3 levels in patients with Fabry disease. Mol Genet Metab. 2018;123:148\u201353.","journal-title":"Mol Genet Metab"},{"key":"3500_CR17","doi-asserted-by":"publisher","first-page":"15","DOI":"10.3390\/diseases5020015","volume":"5","author":"I Beir\u00e3o","year":"2017","unstructured":"Beir\u00e3o I, Cabrita A, Torres M, Silva F, Aguiar P, Laranjeira F, et al. Biomarkers and Imaging Findings of Anderson\u2013Fabry Disease\u2013What We Know Now. Diseases. 2017;5:15.","journal-title":"Diseases"},{"issue":"10","key":"3500_CR18","doi-asserted-by":"publisher","first-page":"5158","DOI":"10.3390\/ijms25105158","volume":"25","author":"G Duro","year":"2024","unstructured":"Duro G, Anania M, Zizzo C, Francofonte D, Giacalone I, D\u2019Errico A, et al. Diagnosis of Fabry disease using alpha-galactosidase A activity or lysoGb3 in blood fails to identify up to two thirds of female patients. Int J Mol Sci. 2024;25(10):5158.","journal-title":"Int J Mol Sci"},{"key":"3500_CR19","first-page":"3733","volume":"15","author":"Y Ouyang","year":"2018","unstructured":"Ouyang Y, Chen B, Pan X, Wang Z, Ren H, Xu Y, et al. Clinical significance of plasma globotriaosylsphingosine levels in Chinese patients with Fabry disease. Exp Ther Med. 2018;15:3733\u201342.","journal-title":"Exp Ther Med"},{"key":"3500_CR20","doi-asserted-by":"publisher","first-page":"107585","DOI":"10.1016\/j.ymgme.2023.107585","volume":"139","author":"A Burlina","year":"2023","unstructured":"Burlina A, Brand E, Hughes D, Kantola I, Kr\u00e4mer J, Nowak A, et al. An expert consensus on the recommendations for the use of biomarkers in Fabry disease. Mol Genet Metab. 2023;139:107585.","journal-title":"Mol Genet Metab"},{"key":"3500_CR21","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1002\/ejhf.1960","volume":"22","author":"A Linhart","year":"2020","unstructured":"Linhart A, Germain DP, Olivotto I, Akhtar MM, Anastasakis A, Hughes D, et al. An expert consensus document on the management of cardiovascular manifestations of Fabry disease. E J Heart Fail. 2020;22:1076\u201396.","journal-title":"E J Heart Fail"},{"issue":"6","key":"3500_CR22","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1016\/j.jcmg.2011.01.020","volume":"4","author":"M Niemann","year":"2011","unstructured":"Niemann M, Herrmann S, Hu K, Breunig F, Strotmann J, Beer M, et al. Differences in Fabry cardiomyopathy between female and male patients: Consequences for diagnostic assessment. JACC Cardiovasc Imaging. 2011;4(6):592\u2013601.","journal-title":"JACC Cardiovasc Imaging"},{"issue":"4S","key":"3500_CR23","first-page":"S117","volume":"105","author":"Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group","year":"2024","unstructured":"Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. 2024;105(4S):S117\u2013314.","journal-title":"Kidney Int"},{"key":"3500_CR24","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1097\/01.gim.0000237866.70357.c6","volume":"8","author":"CM Eng","year":"2006","unstructured":"Eng CM, Germain DP, Banikazemi M, Warnock DG, Wanner C, Hopkin RJ, et al. Fabry disease: guidelines for the evaluation and management of multi-organ system involvement. Genet Med. 2006;8:539\u201348.","journal-title":"Genet Med"},{"key":"3500_CR25","unstructured":"Hughes D and members of the LSD expert advisory group. Adult Fabry disease standard operating procedures (England) 2013. http:\/\/www.edrep.org\/media\/download_gallery\/SOP_for_Anderson_Fabry_disease.pdf"},{"issue":"1","key":"3500_CR26","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1093\/ndt\/gfad164","volume":"38","author":"A Pisani","year":"2023","unstructured":"Pisani A, Pieruzzi F, Cirami CL, Riccio E, Mignani R. Interpretation of GFR slope in untreated and treated adult Fabry patients. Nephrol Dial Tranplant. 2023;38(1):18\u201325.","journal-title":"Nephrol Dial Tranplant"},{"key":"3500_CR27","first-page":"13","volume":"38","author":"N Ali","year":"2018","unstructured":"Ali N, Gillespie S, Laney D. Treatment of Depression in Adults with Fabry Disease. JIMD Rep. 2018;38:13\u201321.","journal-title":"JIMD Rep"},{"key":"3500_CR28","first-page":"100497","volume":"20","author":"MA Hossain","year":"2019","unstructured":"Hossain MA, Wu C, Yanagisawa H, Miyajima T, Akiyama K, Eto Y. Future clinical and biochemical predictions of Fabry disease in females by methylation studies of the GLA gene. Mol Genet Metab Rep. 2019;20:100497.","journal-title":"Mol Genet Metab Rep"},{"key":"3500_CR29","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/j.ymgme.2017.01.002","volume":"120","author":"MA Hossain","year":"2017","unstructured":"Hossain MA, Yanagisawa H, Miyajima T, Wu C, Takamura A, Itagaki R, et al. The severe clinical phenotype for a heterozygous Fabry female patient correlates to the methylation of non-mutated allele associated with chromosome 10q26 deletion syndrome. Mol Genet Metab. 2017;120:173\u20139.","journal-title":"Mol Genet Metab"},{"issue":"1\u20132","key":"3500_CR30","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.ymgme.2020.07.007","volume":"131","author":"U Feldt-Rasmussen","year":"2020","unstructured":"Feldt-Rasmussen U, Hughes D, Sunder-Plassmann G, Shankar S, Need K, Olivotto I, et al. Long-term efficacy and safety of migalastat treatment in Fabry disease: 30-month results from the open-label extension of the randomized, phase 3 ATTRACT study. Mol Genet Metab. 2020;131(1\u20132):219\u201328.","journal-title":"Mol Genet Metab"},{"key":"3500_CR31","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1093\/ndt\/gfx009","volume":"33","author":"A Pisani","year":"2018","unstructured":"Pisani A, Annicchiarico LP, Pellegrino A, Bruzzese D, Feriozzi S, Imbriaco M, et al. Parapelvic cysts, a distinguishing feature of renal Fabry disease. Nephrol Dial Transplant. 2018;33:318\u201323.","journal-title":"Nephrol Dial Transplant"},{"key":"3500_CR32","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1159\/000493469","volume":"141","author":"E Riccio","year":"2019","unstructured":"Riccio E, Sabbatini M, Bruzzese D, Petruzzelli LA, Pellegrino A, Spinelli L, et al. Glomerular Hyperfiltration: An Early Marker of Nephropathy in Fabry Disease. Nephron. 2019;141:10\u201317.","journal-title":"Nephron"},{"key":"3500_CR33","doi-asserted-by":"publisher","first-page":"7758","DOI":"10.18632\/oncotarget.23970","volume":"9","author":"P Colomba","year":"2018","unstructured":"Colomba P, Zizzo C, Alessandro R, Cammarata G, Scalia S, Giordano A, et al. Fabry disease and multiple sclerosis misdiagnosis: the role of family history and neurological signs. Oncotarget. 2018;9:7758\u201362.","journal-title":"Oncotarget"},{"key":"3500_CR34","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1016\/j.dld.2018.02.011","volume":"50","author":"MJ Hilz","year":"2018","unstructured":"Hilz MJ, Arbustini E, Dagna L, Gasbarrini A, Goizet C, Lacombe D, et al. Non-specific gastrointestinal features: Could it be Fabry disease? Dig Liver Dis. 2018;50:429\u201337.","journal-title":"Dig Liver Dis"},{"key":"3500_CR35","doi-asserted-by":"publisher","first-page":"3021","DOI":"10.1093\/eurheartj\/ehy339","volume":"39","author":"B Williams","year":"2018","unstructured":"Williams B, Mancia G, Spiering W, Rosei EA, Azizi M, Burnier M, et al. 2018 ESC\/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39:3021\u2013104.","journal-title":"Eur Heart J"},{"issue":"12","key":"3500_CR36","doi-asserted-by":"publisher","first-page":"1874","DOI":"10.1097\/HJH.0000000000003480","volume":"41","author":"G Mancia","year":"2023","unstructured":"Mancia G, Kreutz R, Brunstr\u00f6m M, Burnier M, Grassi G, Januszewicz A, et al. 2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension: Endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA). J Hypertens. 2023;41(12):1874\u20132071.","journal-title":"J Hypertens"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-024-03500-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-024-03500-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-024-03500-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T13:23:44Z","timestamp":1750339424000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-024-03500-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,7]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["3500"],"URL":"https:\/\/doi.org\/10.1186\/s13023-024-03500-7","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,7]]},"assertion":[{"value":"28 March 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 December 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 January 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All procedures followed for the patient interviews were in accordance with the Helsinki Declaration 1975. Informed consent was obtained from all patients interviewed.","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":"Eva Brand received research grants and speaker\/consulting honoraria from Amicus Therapeutics, Chiesi, Sanofi, and Takeda. Ale\u0161 Linhart received speakers and consulting fees from Amicus Therapeutics, Chiesi, Sanofi, and Takeda. Patrick Deegan received speaker\/consulting honoraria from Amicus Therapeutics, Chiesi, Sanofi and Takeda, and research grants from Sanofi and Takeda. Ruxandra Jurcut received non-restrictive educational grants and speaker fees from Genesis Pharma (representing Amicus), Sanofi, and Takeda. Antonio Pisani received travel expenses and grants from Amicus, Sanofi, Chiesi-Protalix and Takeda-Shire. Roser Torra received speaker\/consulting honoraria from Amicus Therapeutics, Chiesi, Sanofi Genzyme, and Takeda. Ulla Feldt-Rasmussen received unrestricted educational grants and speaker\/consulting honoraria from Amicus Therapeutics, Chiesi, Freeline, Sanofi, and Takeda; Ulla Feldt-Rasmussen also received a research salary that was supported by a grant from Kirsten and Freddy Johansen\u2019s Fund.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"7"}}