{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:45:40Z","timestamp":1791942340690,"version":"4.3.4"},"reference-count":82,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T00:00:00Z","timestamp":1694736000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Catania"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Anderson\u2013Fabry Disease (AFD) is a rare, systemic lysosomal storage disease triggered by mutations in the GLA gene, leading to \u03b1-galactosidase A (\u03b1-Gal A) deficiency. The disease\u2019s X-linked inheritance leads to more severe, early-onset presentations in males, while females exhibit variable, often insidious, manifestations, notably impacting cardiac health. This study aims to examine gender-based AFD cardiac manifestations in correlation with the variant type: classical (CL), late-onset (LO), or variants of uncertain significance (VUS). We analyzed data from 72 AFD patients (53 females, 19 males) referred to the \u201cG. Rodolico\u201d University Hospital, employing enzyme activity measurements, genetic analysis, periodic lyso-Gb3 monitoring, comprehensive medical histories, and advanced cardiac imaging techniques. Statistical analysis was performed using SPSS version 26. Our AFD cohort, with an average age of 45 \u00b1 16.1 years, comprised 12 individuals with hypertrophy (AFD-LVH) and 60 without (AFD-N). Women, representing about 75% of the subjects, were generally older than men (47.2 \u00b1 16.2 vs. 38.8 \u00b1 14.6, p = 0.046). In the female group, 17% had CL variants, 43.3% LO, and 39.6% had VUS, compared to 21.1%, 36.8%, and 31.6% in the male group, respectively. Females exhibited significantly higher \u03b1-Gal A values (median 7.9 vs. 1.8 nmol\/mL\/h, p &lt; 0.001) and lower lyso-Gb3 levels (1.5 [IQR 1.1\u20131.7] vs. 1.9 [1.5\u201317.3] nmol\/L, p = 0.02). Regarding the NYHA class distribution, 70% of women were in class I and 28% in class II, compared to 84% and 16% of men, respectively. Among women, 7.5% exhibited ventricular arrhythmias (10.5% in men), and 9.4% had atrial fibrillation (10.5% in men). Cardiac MRIs revealed fibrosis in 57% of examined women, compared to 87% of men. Even among patients without LVH, significant differences persisted in \u03b1-Gal A and lyso-Gb3 levels (p = 0.003 and 0.04), as well as LVMi (61.5 vs. 77.5 g\/sqm, p = 0.008) and GLS values (\u221220% vs. \u221217%, p = 0.01). The analysis underscored older age, decreased lyso-Gb3 deposition, reduced hypertrophy, and lesser GLS compromise in females, suggesting later disease onset. Severe cardiac patterns were associated with classic variants, while more nuanced manifestations were noted in those with VUS. Early GLS impairment in males, irrespective of hypertrophy, emphasized the role of subclinical damage in AFD.<\/jats:p>","DOI":"10.3390\/genes14091804","type":"journal-article","created":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T06:36:45Z","timestamp":1694932605000},"page":"1804","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Sex Differences in Anderson\u2013Fabry Cardiomyopathy: Clinical, Genetic, and Imaging Analysis in Women"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6568-6176","authenticated-orcid":false,"given":"Denise Cristiana","family":"Faro","sequence":"first","affiliation":[{"name":"Department of Surgery and Medical-Surgical Specialties, University of Catania, Via Santa Sofia 78, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9328-4417","authenticated-orcid":false,"given":"Valentina","family":"Losi","sequence":"additional","affiliation":[{"name":"Department of Surgery and Medical-Surgical Specialties, University of Catania, Via Santa Sofia 78, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6878-9779","authenticated-orcid":false,"given":"Margherita Stefania","family":"Rodolico","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation, National Research Council (IRIB-CNR), Section of Catania, Via P. Gaifami 18, 95126 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvira Mariateresa","family":"Torrisi","sequence":"additional","affiliation":[{"name":"Department of Surgery and Medical-Surgical Specialties, University of Catania, Via Santa Sofia 78, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2470-7030","authenticated-orcid":false,"given":"Paolo","family":"Colomba","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation, National Research Council (IRIB-CNR), Via Ugo La Malfa 153, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Duro","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation, National Research Council (IRIB-CNR), Via Ugo La Malfa 153, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7059-7525","authenticated-orcid":false,"given":"Ines Paola","family":"Monte","sequence":"additional","affiliation":[{"name":"Department of Surgery and Medical-Surgical Specialties, University of Catania, Via Santa Sofia 78, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.ymgme.2018.02.014","article-title":"Fabry disease revisited: Management and treatment recommendations for adult patients","volume":"123","author":"Ortiz","year":"2018","journal-title":"Mol. Genet. Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"s10","DOI":"10.1590\/1806-9282.66.s1.10","article-title":"Fabry disease: Genetics, pathology, and treatment","volume":"66","author":"Bernardes","year":"2020","journal-title":"Rev. Assoc. Med. Bras."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1038\/ejhg.2017.17","article-title":"Clinical utility gene card for: Fabry disease\u2014Update 2016","volume":"25","author":"Gal","year":"2017","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1136\/jmedgenet-2017-105080","article-title":"Fabry Disease: Prevalence of affected males and heterozygotes with pathogenic GLA mutations identified by screening renal, cardiac and stroke clinics, 1995\u20132017","volume":"55","author":"Doheny","year":"2018","journal-title":"J. Med. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1111\/cge.14102","article-title":"Challenging the traditional approach for interpreting genetic variants: Lessons from Fabry disease","volume":"101","author":"Germain","year":"2022","journal-title":"Clin. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_7","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_8","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1111\/cge.12613","article-title":"X-chromosome inactivation in female patients with Fabry disease","volume":"89","author":"Echevarria","year":"2016","journal-title":"Clin. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1007\/s00109-005-0656-2","article-title":"Relationship between X-inactivation and clinical involvement in Fabry heterozygotes. Eleven novel mutations in the alpha-galactosidase A gene in the Czech and Slovak population","volume":"83","author":"Dobrovolny","year":"2005","journal-title":"J. Mol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1002\/ejhf.1960","article-title":"An expert consensus document on the management of cardiovascular manifestations of Fabry disease","volume":"22","author":"Linhart","year":"2020","journal-title":"Eur. J. Heart Fail."},{"key":"ref_11","unstructured":"Arbelo, E., Protonotarios, A., Gimeno, J.R., Arbustini, E., Barriales-Villa, R., Basso, C., Bezzina, C.R., Biagini, E., Blom, N.A., and de Boer, R.A. (2023). 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). Eur. Heart J., ehad194. Online ahead of print."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.ymgme.2011.07.014","article-title":"The use of dried blood spot samples in the diagnosis of lysosomal storage disorders\u2014Current status and perspectives","volume":"104","author":"Reuser","year":"2011","journal-title":"Mol. Genet. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.bbadis.2010.05.003","article-title":"Plasma globotriaosylsphingosine: Diagnostic value and relation to clinical manifestations of Fabry disease","volume":"1802","author":"Rombach","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1093\/eurheartj\/ehv122","article-title":"The current role of next-generation DNA sequencing in routine care of patients with hereditary cardiovascular conditions: A viewpoint paper of the European Society of Cardiology working group on myocardial and pericardial diseases and members of the European Society of Human Genetics","volume":"36","author":"Mogensen","year":"2015","journal-title":"Eur. Heart J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.ijcard.2014.09.001","article-title":"Uncertain diagnosis of Fabry disease: Consensus recommendation on diagnosis in adults with left ventricular hypertrophy and genetic variants of unknown significance","volume":"177","author":"Smid","year":"2014","journal-title":"Int. J. Cardiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/cge.13546","article-title":"Consensus recommendations for diagnosis, management and treatment of Fabry disease in paediatric patients","volume":"96","author":"Germain","year":"2019","journal-title":"Clin. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"650","DOI":"10.21037\/cdt-20-593","article-title":"Narrative review on Morbus Fabry: Diagnosis and management of cardiac manifestations","volume":"11","author":"Linhart","year":"2021","journal-title":"Cardiovasc. Diagn. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1002\/jgf2.76","article-title":"Fabry disease and its cardiac involvement","volume":"18","author":"Kubo","year":"2017","journal-title":"J. Gen. Fam. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"f153","DOI":"10.1093\/europace\/eux261","article-title":"Ventricular arrhythmia and sudden cardiac death in Fabry disease: A systematic review of risk factors in clinical practice","volume":"20","author":"Baig","year":"2018","journal-title":"Europace"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1002\/mgg3.389","article-title":"Phenotypic characteristics of the p.Asn215Ser (p.N215S) GLA mutation in male and female patients with Fabry disease: A multicenter Fabry Registry study","volume":"6","author":"Germain","year":"2018","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"196","DOI":"10.31083\/j.rcm2306196","article-title":"The Heart in Fabry Disease: Mechanisms Beyond Storage and Forthcoming Therapies","volume":"23","author":"Pieroni","year":"2022","journal-title":"Rev. Cardiovasc. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1016\/j.jcmg.2018.03.020","article-title":"Proposed Stages of Myocardial Phenotype Development in Fabry Disease","volume":"12","author":"Nordin","year":"2019","journal-title":"JACC Cardiovasc. Imaging"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e009430","DOI":"10.1161\/CIRCIMAGING.119.009430","article-title":"Myocardial Storage, Inflammation, and Cardiac Phenotype in Fabry Disease After One Year of Enzyme Replacement Therapy","volume":"12","author":"Nordin","year":"2019","journal-title":"Circ. Cardiovasc. Imaging"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.ultrasmedbio.2010.10.017","article-title":"Prominent papillary muscles in Fabry disease: A diagnostic marker?","volume":"37","author":"Niemann","year":"2011","journal-title":"Ultrasound Med. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1093\/eurheartj\/ehm153","article-title":"Cardiac manifestations of Anderson-Fabry disease: Results from the international Fabry outcome survey","volume":"28","author":"Linhart","year":"2007","journal-title":"Eur. Heart J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1080\/10976640600605002","article-title":"The histological basis of late gadolinium enhancement cardiovascular magnetic resonance in a patient with Anderson-Fabry disease","volume":"8","author":"Moon","year":"2006","journal-title":"J. Cardiovasc. Magn. Reson."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s13023-021-02133-4","article-title":"Cardiac device implantation and device usage in Fabry and hypertrophic cardiomyopathy","volume":"17","author":"Vijapurapu","year":"2022","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"201","DOI":"10.31083\/j.rcm2306201","article-title":"Echocardiography in Anderson-Fabry Disease","volume":"23","author":"Lillo","year":"2022","journal-title":"Rev. Cardiovasc. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1111\/echo.14592","article-title":"Mechanical dispersion in Fabry disease assessed with speckle tracking echocardiography","volume":"37","author":"Cianciulli","year":"2020","journal-title":"Echocardiography"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/j.jcmg.2019.03.025","article-title":"Prediction of Ventricular Arrhythmias With Left Ventricular Mechanical Dispersion: A Systematic Review and Meta-Analysis","volume":"13","author":"Kawakami","year":"2020","journal-title":"JACC Cardiovasc. Imaging"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"oead014","DOI":"10.1093\/ehjopen\/oead014","article-title":"Speckle tracking echocardiography-derived parameters as new prognostic markers in hypertrophic cardiomyopathies","volume":"3","author":"Faro","year":"2023","journal-title":"Eur. Heart J. Open"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Duro, G., Zizzo, C., Cammarata, G., Burlina, A., Burlina, A., Polo, G., Scalia, S., Oliveri, R., Sciarrino, S., and Francofonte, D. (2018). Mutations in the GLA Gene and LysoGb3: Is It Really Anderson-Fabry Disease?. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19123726"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1136\/jmedgenet-2019-106467","article-title":"Use of a rare disease registry for establishing phenotypic classification of previously unassigned GLA variants: A consensus classification system by a multispecialty Fabry disease genotype\u2013phenotype workgroup","volume":"57","author":"Germain","year":"2020","journal-title":"J. Med. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.echo.2016.01.011","article-title":"Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging","volume":"29","author":"Nagueh","year":"2016","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1093\/ehjci\/jey042","article-title":"Standardization of left atrial, right ventricular, and right atrial deformation imaging using two-dimensional speckle tracking echocardiography: A consensus document of the EACVI\/ASE\/Industry Task Force to standardize deformation imaging","volume":"19","author":"Badano","year":"2018","journal-title":"Eur. Heart J. Cardiovasc. Imaging"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1093\/ehjci\/jex244","article-title":"Standardization of adult transthoracic echocardiography reporting in agreement with recent chamber quantification, diastolic function, and heart valve disease recommendations: An expert consensus document of the European Association of Cardiovascular Imaging","volume":"18","author":"Galderisi","year":"2017","journal-title":"Eur. Heart J. Cardiovasc. Imaging"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Moura, B., Aimo, A., Al-Mohammad, A., Keramida, K., Ben Gal, T., Dorbala, S., Todiere, G., Cameli, M., Barison, A., and Bayes-Genis, A. (2023). Diagnosis and management of patients with left ventricular hypertrophy: Role of multimodality cardiac imaging. A scientific statement of the Heart Failure Association of the European Society of Cardiology. Eur. J. Heart Fail., Online ahead of print.","DOI":"10.1002\/ejhf.2997"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e7387","DOI":"10.1097\/MD.0000000000007387","article-title":"Clinical characteristics and mutation spectrum of GLA in Korean patients with Fabry disease by a nationwide survey: Underdiagnosis of late-onset phenotype","volume":"96","author":"Choi","year":"2017","journal-title":"Medicine"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1007\/BF03401671","article-title":"Fabry disease: Thirty-five mutations in the alpha-galactosidase A gene in patients with classic and variant phenotypes","volume":"3","author":"Eng","year":"1997","journal-title":"Mol. Med."},{"key":"ref_40","first-page":"784","article-title":"Identification of point mutations in the alpha-galactosidase A gene in classical and atypical hemizygotes with Fabry disease","volume":"47","author":"Sakuraba","year":"1990","journal-title":"Am. J. Hum. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s13023-022-02599-w","article-title":"The Spanish Fabry women study: A retrospective observational study describing the phenotype of females with GLA variants","volume":"18","author":"Gimeno","year":"2023","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1136\/heartjnl-2020-317922","article-title":"Influence of sex and phenotype on cardiac outcomes in patients with Fabry disease","volume":"107","author":"Hirsch","year":"2021","journal-title":"Heart"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/j.jcmg.2011.01.020","article-title":"Differences in Fabry cardiomyopathy between female and male patients: Consequences for diagnostic assessment","volume":"4","author":"Niemann","year":"2011","journal-title":"JACC Cardiovasc. Imaging"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.ymgme.2018.11.005","article-title":"Early detection of organ involvement in Fabry disease by biomarker assessment in conjunction with LGE cardiac MRI: Results from the SOPHIA study","volume":"126","author":"Weidemann","year":"2019","journal-title":"Mol. Genet. Metab."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1159\/000330924","article-title":"Left ventricular noncompaction in a patient with fabry disease: Overdiagnosis, morphological manifestation of fabry disease or two unrelated rare conditions in the same patient?","volume":"119","author":"Azevedo","year":"2011","journal-title":"Cardiology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.repc.2019.02.014","article-title":"Screening for Fabry disease in patients with left ventricular noncompaction","volume":"38","author":"Azevedo","year":"2019","journal-title":"Rev. Port. Cardiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.amjcard.2014.06.019","article-title":"Relation of burden of myocardial fibrosis to malignant ventricular arrhythmias and outcomes in Fabry disease","volume":"114","author":"Niemann","year":"2014","journal-title":"Am. J. Cardiol."},{"key":"ref_48","first-page":"8","article-title":"\u201cEffetto donna\u201d nelle cardiomiopatie","volume":"13","author":"Biagini","year":"2012","journal-title":"G. Ital. Cardiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1750-1172-5-30","article-title":"Fabry disease","volume":"5","author":"Germain","year":"2010","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_50","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_51","doi-asserted-by":"crossref","first-page":"5809","DOI":"10.1038\/s41598-023-32464-0","article-title":"Comparison of classical Fabry and its p.D313Y and p.A143T variants by cardiac T1 mapping, LGE and feature tracking myocardial strain","volume":"13","author":"Avanesov","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1136\/heartjnl-2018-313699","article-title":"Global longitudinal strain, myocardial storage and hypertrophy in Fabry disease","volume":"105","author":"Vijapurapu","year":"2019","journal-title":"Heart"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"100565","DOI":"10.1016\/j.ymgmr.2020.100565","article-title":"Natural history of the late-onset phenotype of Fabry disease due to the p.F113L mutation","volume":"22","author":"Azevedo","year":"2020","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"185","DOI":"10.5414\/CNP61185","article-title":"A nonsense mutation (R220X) in the alpha-galactosidase A gene causes typical Fabry disease in both genders","volume":"61","author":"Maki","year":"2004","journal-title":"Clin. Nephrol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Monte, M.A., Veroux, M., Rodolico, M.S., Losi, V., Di Pino, L., Bella, R., Lanza, G., and Monte, I.P. (2022). Fabry\u2019s Disease: The Utility of a Multidisciplinary Screening Approach. Life, 12.","DOI":"10.3390\/life12050623"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.gene.2015.12.024","article-title":"Molecular and clinical studies in five index cases with novel mutations in the GLA gene","volume":"578","author":"Zizzo","year":"2016","journal-title":"Gene"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Iemolo, F., Pizzo, F., Albeggiani, G., Zizzo, C., Colomba, P., Scalia, S., Bartolotta, C., and Duro, G. (2014). De novo mutation in a male patient with Fabry disease: A case report. BMC Res. Notes, 7.","DOI":"10.1186\/1756-0500-7-11"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"504784","DOI":"10.1155\/2015\/504784","article-title":"High Variability of Fabry Disease Manifestations in an Extended Italian Family","volume":"2015","author":"Cammarata","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1038\/gim.2016.55","article-title":"Is it Fabry disease?","volume":"18","author":"Schiffmann","year":"2016","journal-title":"Genet. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1080\/0886022X.2016.1254656","article-title":"Screening Fabry\u2019s disease in chronic kidney disease patients not on dialysis: A multicenter study","volume":"39","author":"Akdam","year":"2017","journal-title":"Ren. Fail."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Lukas, J., Giese, A.K., Markoff, A., Grittner, U., Kolodny, E., Mascher, H., Lackner, K.J., Meyer, W., Wree, P., and Saviouk, V. (2013). Functional Characterisation of alpha-Galactosidase A Mutations as a Basis for a New Classification System in Fabry Disease. PLoS Genet., 9.","DOI":"10.1371\/journal.pgen.1003632"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e017098","DOI":"10.1136\/bmjopen-2017-017098","article-title":"Fabry disease due to D313Y and novel GLA mutations","volume":"7","author":"Koulousios","year":"2017","journal-title":"BMJ Open"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S1096-7192(03)00136-7","article-title":"Fabry disease: D313Y is an \u03b1-galactosidase A sequence variant that causes pseudodeficient activity in plasma","volume":"80","author":"Froissart","year":"2003","journal-title":"Mol. Genet. Metab."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"338","DOI":"10.7326\/0003-4819-138-4-200302180-00014","article-title":"Fabry disease, an under-recognized multisystemic disorder: Expert recommendations for diagnosis, management, and enzyme replacement therapy","volume":"138","author":"Desnick","year":"2003","journal-title":"Ann. Intern. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1097\/GIM.0b013e31802d8321","article-title":"Heterozygous Fabry women are not just carriers, but have a significant burden of disease and impaired quality of life","volume":"9","author":"Wang","year":"2007","journal-title":"Genet. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e2029","DOI":"10.1002\/mgg3.2029","article-title":"X-chromosomal inactivation patterns in women with Fabry disease","volume":"10","author":"Rickert","year":"2022","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"De Riso, G., Cuomo, M., Di Risi, T., Della Monica, R., Buonaiuto, M., Costabile, D., Pisani, A., Cocozza, S., and Chiariotti, L. (2020). Ultra-Deep DNA Methylation Analysis of X-Linked Genes: GLA and AR as Model Genes. Genes, 11.","DOI":"10.3390\/genes11060620"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s13148-021-01019-3","article-title":"DNA methylation impact on Fabry disease","volume":"13","author":"Vinciguerra","year":"2021","journal-title":"Clin. Epigenetics"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1002\/ehf2.12647","article-title":"Cardiomyopathy and kidney function in agalsidase beta-treated female Fabry patients: A pre-treatment vs. post-treatment analysis","volume":"7","author":"Wanner","year":"2020","journal-title":"ESC Heart Fail."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s10545-017-0127-2","article-title":"Globotriaosylsphingosine (Lyso-Gb(3)) as a biomarker for cardiac variant (N215S) Fabry disease","volume":"41","author":"Alharbi","year":"2018","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.bbadis.2010.09.007","article-title":"Reduction of elevated plasma globotriaosylsphingosine in patients with classic Fabry disease following enzyme replacement therapy","volume":"1812","author":"Rombach","year":"2011","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Basis Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.ymgme.2017.06.006","article-title":"Correlation of Lyso-Gb3 levels in dried blood spots and sera from patients with classic and Later-Onset Fabry disease","volume":"121","author":"Nowak","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.cca.2017.01.018","article-title":"Biomarkers associated with clinical manifestations in Fabry disease patients with a late-onset cardiac variant mutation","volume":"466","author":"Lavoie","year":"2017","journal-title":"Clin. Chim. Acta"},{"key":"ref_74","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_75","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1136\/jmedgenet-2015-103486","article-title":"Time to treatment benefit for adult patients with Fabry disease receiving agalsidase \u03b2: Data from the Fabry Registry","volume":"53","author":"Ortiz","year":"2016","journal-title":"J. Med. Genet."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1136\/jmedgenet-2020-107338","article-title":"Lyso-Gb3 associates with adverse long-term outcome in patients with Fabry disease","volume":"59","author":"Nowak","year":"2022","journal-title":"J. Med. Genet."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/gim.2018.31","article-title":"Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis","volume":"21","author":"Maruyama","year":"2019","journal-title":"Genet. Med."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Hsu, T.R., Chang, F.P., Chu, T.H., Sung, S.H., Bizjajeva, S., Yu, W.C., and Niu, D.M. (2017). Correlations between Endomyocardial Biopsies and Cardiac Manifestations in Taiwanese Patients with the Chinese Hotspot IVS4+919G>A Mutation: Data from the Fabry Outcome Survey. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18010119"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/s13023-015-0338-2","article-title":"Effectiveness of agalsidase alfa enzyme replacement in Fabry disease: Cardiac outcomes after 10 years\u2019 treatment","volume":"10","author":"Kampmann","year":"2015","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3705","DOI":"10.2147\/DDDT.S207856","article-title":"Cardio- Renal Outcomes With Long- Term Agalsidase Alfa Enzyme Replacement Therapy: A 10- Year Fabry Outcome Survey (FOS) Analysis","volume":"13","author":"Ramaswami","year":"2019","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1002\/cpt.1832","article-title":"Treatment of Fabry\u2019s Disease With Migalastat: Outcome From a Prospective Observational Multicenter Study (FAMOUS)","volume":"108","author":"Lenders","year":"2020","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.ymgme.2011.03.022","article-title":"Response of women with Fabry disease to enzyme replacement therapy: Comparison with men, using data from FOS\u2014the Fabry Outcome Survey","volume":"103","author":"Hughes","year":"2011","journal-title":"Mol. Genet. Metab."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/9\/1804\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:51:50Z","timestamp":1760129510000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/9\/1804"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,15]]},"references-count":82,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["genes14091804"],"URL":"https:\/\/doi.org\/10.3390\/genes14091804","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,15]]}}}