{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:46:34Z","timestamp":1791942394081,"version":"4.3.4"},"reference-count":118,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T00:00:00Z","timestamp":1665532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Fabry disease (FD) (OMIM #301500) is a rare genetic lysosomal storage disorder (LSD). LSDs are characterized by inappropriate lipid accumulation in lysosomes due to specific enzyme deficiencies. In FD, the defective enzyme is \u03b1-galactosidase A (\u03b1-Gal A), which is due to a mutation in the GLA gene on the X chromosome. The enzyme deficiency leads to a continuous deposition of neutral glycosphingolipids (globotriaosylceramide) in the lysosomes of numerous tissues and organs, including endothelial cells, smooth muscle cells, corneal epithelial cells, renal glomeruli and tubules, cardiac muscle and ganglion cells of the nervous system. This condition leads to progressive organ failure and premature death. The increasing understanding of FD, and LSD in general, has led in recent years to the introduction of enzyme replacement therapy (ERT), which aims to slow, if not halt, the progression of the metabolic disorder. In this review, we provide an overview of the main features of FD, focusing on its molecular mechanism and the role of biomarkers.<\/jats:p>","DOI":"10.3390\/biom12101460","type":"journal-article","created":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T20:53:29Z","timestamp":1665608009000},"page":"1460","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["An Overview of Molecular Mechanisms in Fabry Disease"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1626-9077","authenticated-orcid":false,"given":"Federica","family":"Amodio","sequence":"first","affiliation":[{"name":"Inherited and Rare Cardiovascular Diseases, Department of Translational Medical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, Monaldi Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3805-4170","authenticated-orcid":false,"given":"Martina","family":"Caiazza","sequence":"additional","affiliation":[{"name":"Inherited and Rare Cardiovascular Diseases, Department of Translational Medical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, Monaldi Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9304-988X","authenticated-orcid":false,"given":"Emanuele","family":"Monda","sequence":"additional","affiliation":[{"name":"Inherited and Rare Cardiovascular Diseases, Department of Translational Medical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, Monaldi Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Rubino","sequence":"additional","affiliation":[{"name":"Inherited and Rare Cardiovascular Diseases, Department of Translational Medical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, Monaldi Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Capodicasa","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Monaldi Hospital, Via L. Bianchi, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1728-6098","authenticated-orcid":false,"given":"Flavia","family":"Chiosi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Monaldi Hospital, Via L. Bianchi, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Simonelli","sequence":"additional","affiliation":[{"name":"Department of Neurology, Monaldi Hospital, Via L. Bianchi, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Dongiglio","sequence":"additional","affiliation":[{"name":"Inherited and Rare Cardiovascular Diseases, Department of Translational Medical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, Monaldi Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9797-8360","authenticated-orcid":false,"given":"Fabio","family":"Fimiani","sequence":"additional","affiliation":[{"name":"Inherited and Rare Cardiovascular Diseases, Department of Translational Medical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, Monaldi Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Pepe","sequence":"additional","affiliation":[{"name":"Molecular Genomics Lab., Chemical Biochemistry Unit, Monaldi Hospital, Via L. Bianchi, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Chimenti","sequence":"additional","affiliation":[{"name":"Area ANMCO Malattie Rare\u2014Dipartimento di Scienze Cliniche Internistiche Anestesiologiche e Cardiovascolari, Universit\u00e0 La Sapienza, 00155 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5018-830X","authenticated-orcid":false,"given":"Paolo","family":"Calabr\u00f2","sequence":"additional","affiliation":[{"name":"Inherited and Rare Cardiovascular Diseases, Department of Translational Medical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, Monaldi Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8291-9517","authenticated-orcid":false,"given":"Giuseppe","family":"Limongelli","sequence":"additional","affiliation":[{"name":"Inherited and Rare Cardiovascular Diseases, Department of Translational Medical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, Monaldi Hospital, 80131 Naples, Italy"},{"name":"Institute of Cardiovascular Sciences, University College of London and St. Bartholomew\u2019s Hospital, London WC1E 6DD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1093\/ndt\/gfg194","article-title":"alpha-Galactosidase A deficiency in Dutch patients on dialysis: A critical appraisal of screening for Fabry disease","volume":"18","author":"Linthorst","year":"2003","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1111\/j.1365-2362.2004.01309.x","article-title":"Fabry disease defined: Baseline clinical manifestations of 366 patients in the Fabry Outcome Survey","volume":"34","author":"Mehta","year":"2004","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_3","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_4","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1016\/j.bbamem.2006.05.027","article-title":"Sphingolipid metabolism diseases","volume":"1758","author":"Kolter","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Belfiore, M.P., Iacobellis, F., Acampora, E., Caiazza, M., Rubino, M., Monda, E., Magaldi, M.R., Tarallo, A., Sasso, M., and De Pasquale, V. (2020). Aortopathies in mouse models of Pompe, Fabry and Mucopolysaccharidosis IIIB lysosomal storage diseases. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0233050"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1086\/316953","article-title":"Fabry Disease: Preclinical Studies Demonstrate the Effectiveness of \u03b1-Galactosidase A Replacement in Enzyme-Deficient Mice","volume":"68","author":"Ioannou","year":"2001","journal-title":"Am. J. Hum. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1056\/NEJM196705252762101","article-title":"Enzymatic defect in Fabry\u2019s disease. Ceramidetrihexosidase deficiency","volume":"276","author":"Brady","year":"1967","journal-title":"N. Engl. J. Med."},{"key":"ref_8","first-page":"131","article-title":"Screening patients with hypertrophic cardiomyopathy for Fabry disease using a filter-paper test: The FOCUS study","volume":"97","author":"Caudron","year":"2010","journal-title":"Heart"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1136\/jmg.38.11.769","article-title":"Anderson-Fabry disease: Clinical manifestations and impact of disease in a cohort of 60 obligate carrier females","volume":"38","author":"MacDermot","year":"2001","journal-title":"J. Med Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1136\/jmg.38.11.750","article-title":"Anderson-Fabry disease: Clinical manifestations and impact of disease in a cohort of 98 hemizygous males","volume":"38","author":"MacDermot","year":"2001","journal-title":"J. Med. Genet."},{"key":"ref_11","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_12","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1136\/jmg.2009.072116","article-title":"Screening for Fabry disease in high-risk populations: A systematic review","volume":"47","author":"Linthorst","year":"2010","journal-title":"J. Med. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.hfc.2021.07.005","article-title":"Diagnosis and Management of Cardiovascular Involvement in Fabry Disease","volume":"18","author":"Rubino","year":"2022","journal-title":"Heart Fail. Clin."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Monda, E., Palmiero, G., Lioncino, M., Rubino, M., Cirillo, A., Fusco, A., Caiazza, M., Verrillo, F., Diana, G., and Mauriello, A. (2022). Multimodality Imaging in Cardiomyopathies with Hypertrophic Phenotypes. J. Clin. Med., 11.","DOI":"10.3390\/jcm11030868"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.ijcard.2019.06.073","article-title":"Prevalence and clinical significance of red flags in patients with hypertrophic cardiomyopathy","volume":"299","author":"Limongelli","year":"2020","journal-title":"Int. J. Cardiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.ijcard.2022.03.050","article-title":"Diagnosis and Management of Rare Cardiomyopathies in Adult and Paediatric Patients. A Position Paper of the Italian Society of Cardiology (SIC) and Italian Society of Paediatric Cardiology (SICP)","volume":"357","author":"Limongelli","year":"2022","journal-title":"Int. J. Cardiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1097\/GIM.0b013e3181bb05bb","article-title":"Life expectancy and cause of death in males and females with Fabry disease: Findings from the Fabry Registry","volume":"11","author":"Waldek","year":"2009","journal-title":"Genet. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1016\/S0140-6736(04)16254-5","article-title":"Recurrent acroparaesthesia during febrile infections","volume":"363","author":"Bodamer","year":"2004","journal-title":"Lancet"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1007\/s00431-003-1299-3","article-title":"The early clinical phenotype of Fabry disease: A study on 35 European children and adolescents","volume":"162","author":"Ries","year":"2003","journal-title":"Eur. J. Pediatr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"S20","DOI":"10.1016\/j.jpeds.2004.01.051","article-title":"Fabry disease in childhood","volume":"144","author":"Desnick","year":"2004","journal-title":"J. Pediatr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e344","DOI":"10.1542\/peds.2004-1678","article-title":"Pediatric Fabry Disease","volume":"115","author":"Ries","year":"2005","journal-title":"Pediatrics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1111\/j.1651-2227.2006.tb02186.x","article-title":"FOS European Investigators. Clinical manifestations of Fabry disease in children: Data from the Fabry Outcome Survey","volume":"95","author":"Ramaswami","year":"2006","journal-title":"Acta Paediatr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1046\/j.1523-1755.2003.00160.x","article-title":"Fabry disease: Detection of undiagnosed hemodialysis patients and identification of a \u201crenal variant\u201d phenotype","volume":"64","author":"Nakao","year":"2003","journal-title":"Kidney Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1097\/00005792-200203000-00003","article-title":"Natural history of Fabry renal disease: Influence of alpha-galactosidase A activity and genetic mutations on clinical course","volume":"81","author":"Branton","year":"2002","journal-title":"Medicine"},{"key":"ref_25","first-page":"113","article-title":"Malattia di Anderson-Fabry: Problematiche diagnostiche, attualit\u00e0 terapeutiche ed esperienza clinica nel trattamento della malattia con terapia enzimatica sostitutiva in pazienti nefropatici [Anderson-Fabry\u2019s disease: Diagnostic problems, therapeutic relevance, and clinical experience in the treatment of the disease with enzyme replacement therapy in nephropathic patients]","volume":"20","author":"Cianciaruso","year":"2003","journal-title":"G. Ital. Nefrol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1016\/S0140-6736(08)61589-5","article-title":"Fabry\u2019s disease","volume":"372","author":"Zarate","year":"2008","journal-title":"Lancet"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1002\/ajmg.a.30123","article-title":"Inheritance of most X-linked traits is not dominant or recessive, just X-linked","volume":"129A","author":"Dobyns","year":"2004","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1136\/jmg.2008.065904","article-title":"Natural course of Fabry disease: Changing pattern of causes of death in FOS\u2014Fabry Outcome Survey","volume":"46","author":"Mehta","year":"2009","journal-title":"J. Med. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/8904_2014_371","article-title":"Innate and Adaptive Immune Response in Fabry Disease","volume":"22","author":"Mauhin","year":"2015","journal-title":"JIMD Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1046\/j.1445-5994.2002.00291.x","article-title":"Clinical features of Fabry\u2019s disease in Australian patients","volume":"32","author":"Galanos","year":"2002","journal-title":"Intern. Med. J."},{"key":"ref_31","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_32","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1080\/08035320600618809","article-title":"Disease manifestations and X inactivation in heterozygous females with Fabry disease","volume":"95","author":"Maier","year":"2006","journal-title":"Acta Paediatr. Suppl."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1002\/humu.9327","article-title":"Thirty-four novel mutations of the GLA gene in 121 patients with Fabry disease","volume":"25","author":"Baron","year":"2005","journal-title":"Hum. Mutat."},{"key":"ref_34","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":"12","author":"Germain","year":"2018","journal-title":"Mol. Genet. Genomic. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1136\/jmg.30.8.658","article-title":"Sequence variations in the first exon of alpha-galactosidase A","volume":"30","author":"Davies","year":"1993","journal-title":"J. Med. Genet."},{"key":"ref_36","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_37","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_38","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/BF00207037","article-title":"Point mutations in the upstream region of the \u03b1-galactosidase A gene exon 6 in an atypical variant of Fabry disease","volume":"89","author":"Ishii","year":"1992","journal-title":"Hum. Genet."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1034\/j.1399-0004.2001.600107.x","article-title":"Identification of fifteen novel mutations and genotype-phenotype relationship in Fabry disease","volume":"60","author":"Altarescu","year":"2001","journal-title":"Clin. Genet."},{"key":"ref_40","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_41","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_42","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_43","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/j.1651-2227.2005.tb02119.x","article-title":"Genotype and phenotype in Fabry disease: Analysis of the Fabry Outcome Survey","volume":"94","author":"Schaefer","year":"2005","journal-title":"Acta Paediatr. Suppl."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1002\/(SICI)1098-1004(1996)8:1<38::AID-HUMU5>3.0.CO;2-L","article-title":"A sensitive mutation screening strategy for Fabry disease: Detection of nine mutations in the alpha-galactosidase A gene","volume":"8","author":"Blanch","year":"1996","journal-title":"Hum. Mutat."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/0014-5793(96)00863-0","article-title":"Only sphingolipid activator protein B (SAP-B or saposin B) stimulates the degradation of globotriaosylceramide by recombinant human lysosomal \u03b1-galactosidase in a detergent-free liposomal system","volume":"393","author":"Kase","year":"1996","journal-title":"FEBS Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"105752","DOI":"10.1016\/j.pep.2020.105752","article-title":"Affinity purification of human alpha galactosidase utilizing a novel small molecule biomimetic of alpha-D-galactose","volume":"177","author":"Dwyer","year":"2021","journal-title":"Protein Expr. Purif."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.jmb.2004.01.035","article-title":"The Molecular Defect Leading to Fabry Disease: Structure of Human \u03b1-Galactosidase","volume":"337","author":"Garman","year":"2004","journal-title":"J. Mol. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1056\/NEJM200107053450102","article-title":"Safety and efficacy of recombinant human alpha-galactosidase A replacement therapy in Fabry\u2019s disease","volume":"345","author":"Eng","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.cca.2022.07.012","article-title":"Functional characterization of novel variants found in patients with suspected Fabry disease","volume":"534","author":"Nicolicht","year":"2022","journal-title":"Clin. Chim. Acta"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1016\/j.jcmg.2018.11.039","article-title":"The Role of Cardiac Imaging in the Diagnosis and Management of Anderson-Fabry Disease","volume":"12","author":"Perry","year":"2019","journal-title":"JACC Cardiovasc. Imaging"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.carpath.2018.11.002","article-title":"Lysosomal storage disorders affecting the heart: A review","volume":"39","author":"Nair","year":"2019","journal-title":"Cardiovasc. Pathol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e008872","DOI":"10.1161\/CIRCIMAGING.119.008872","article-title":"Quantitative Myocardial Perfusion in Fabry Disease","volume":"12","author":"Knott","year":"2019","journal-title":"Circ. Cardiovasc. Imaging"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Ivanova, M. (2020). Altered Sphingolipids Metabolism Damaged Mitochondrial Functions: Lessons Learned From Gaucher and Fabry Diseases. J. Clin. Med., 9.","DOI":"10.3390\/jcm9041116"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.2353\/ajpath.2008.070576","article-title":"Myofilament Degradation and Dysfunction of Human Cardiomyocytes in Fabry Disease","volume":"172","author":"Chimenti","year":"2008","journal-title":"Am. J. Pathol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.stemcr.2019.07.004","article-title":"A Human Stem Cell Model of Fabry Disease Implicates LIMP-2 Accumulation in Cardiomyocyte Pathology","volume":"13","author":"Birket","year":"2019","journal-title":"Stem Cell Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3389\/fcvm.2016.00007","article-title":"Electrocardiographic Changes and Arrhythmia in Fabry Disease","volume":"3","author":"Namdar","year":"2016","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/s41572-019-0089-9","article-title":"Publisher Correction: Lysosomal storage diseases","volume":"5","author":"Platt","year":"2019","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.ymgme.2017.09.004","article-title":"Contribution of inflammatory pathways to Fabry disease pathogenesis","volume":"122","author":"Rozenfeld","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5720","DOI":"10.1093\/hmg\/ddv291","article-title":"Lyso-Gb3 activates Notch1 in human podocytes","volume":"24","author":"Carpio","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e009098","DOI":"10.1161\/JAHA.118.009098","article-title":"Elevated Inflammatory Plasma Biomarkers in Patients With Fabry Disease: A Critical Link to Heart Failure With Preserved Ejection Fraction","volume":"7","author":"Yogasundaram","year":"2018","journal-title":"J. Am. Heart Assoc."},{"key":"ref_61","unstructured":"Mehta, A., Beck, M., and Sunder-Plassmann, G. (2006). Fabry Disease: Perspectives from 5 Years of FOS, Oxford Pharma Genesis."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Viggiano, E., and Politano, L. (2021). X Chromosome Inactivation in Carriers of Fabry Disease: Review and Meta-Analysis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147663"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.jjcc.2010.12.004","article-title":"Identification of novel mutations in the \u03b1-galactosidase A gene in patients with Fabry disease: Pitfalls of mutation analyses in patients with low \u03b1-galactosidase A activity","volume":"57","author":"Makoto","year":"2011","journal-title":"J. Cardiol."},{"key":"ref_64","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_65","doi-asserted-by":"crossref","first-page":"S209","DOI":"10.1016\/S0248-8663(10)70013-8","article-title":"X-linked inheritance and its implication in the diagnosis and management of female patients in Fabry disease","volume":"31","author":"Germain","year":"2010","journal-title":"Rev. Med. Interne"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1126\/science.155.3758.86","article-title":"Diagnosis of gaucher\u2019s disease and niemann-pick disease with small samples of venous blood","volume":"155","author":"Kampine","year":"1967","journal-title":"Science"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/0002-9343(71)90249-X","article-title":"Identification of heterozygous carriers of lipid storage diseases. Current status and clinical applications","volume":"51","author":"Brady","year":"1971","journal-title":"Am. J. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1007\/s11011-022-00942-5","article-title":"A rare cause of hydrops fetalis in two Gaucher disease type 2 patients with a novel mutation","volume":"37","author":"Basaranoglu","year":"2022","journal-title":"Metab. Brain Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1046\/j.1523-1755.2003.00196.x","article-title":"How to improve the early diagnosis of Fabry\u2019s disease?","volume":"64","year":"2003","journal-title":"Kidney Int."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2743","DOI":"10.1001\/jama.285.21.2743","article-title":"Enzyme replacement therapy in Fabry disease: A randomized controlled trial","volume":"285","author":"Schiffmann","year":"2001","journal-title":"JAMA"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Jehn, U., Bayraktar, S., Pollmann, S., Van Marck, V., Weide, T., Pavenst\u00e4dt, H., Brand, E., and Lenders, M. (2021). \u03b1-Galactosidase a Defi-ciency in Fabry Disease Leads to Extensive Dysregulated Cellular Signaling Pathways in Human Podocytes. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111339"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S1096-7192(03)00136-7","article-title":"Fabry disease: D313Y is an alpha-galactosidase A sequence variant that causes pseudodeficient activity in plasma","volume":"80","author":"Froissart","year":"2003","journal-title":"Mol. Genet. Metab."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1016\/j.clinbiochem.2012.04.030","article-title":"Comparison between alpha-galactosidase A activity in blood samples collected on filter paper, leukocytes and plasma","volume":"45","author":"Daitx","year":"2012","journal-title":"Clin. Biochem."},{"key":"ref_74","first-page":"0185-22","article-title":"Recurrent Cerebrovascular Complications under Enzyme Replacement Therapy in a Patient with Fabry Disease on Peritoneal Dialysis","volume":"10","author":"Muto","year":"2022","journal-title":"Intern. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/0009-8981(81)90384-3","article-title":"Differential assay for lysosomal alpha-galactosidases in human tissues and its application to Fabry\u2019s disease","volume":"112","author":"Mayes","year":"1981","journal-title":"Clin. Chim. Acta"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1515\/CCLM.2005.219","article-title":"Deficient \u03b1-galactosidase A activity in plasma but no Fabry disease\u2014A pitfall in diagnosis","volume":"43","author":"Hoffmann","year":"2005","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0009-8981(01)00478-8","article-title":"Fabry disease: Enzymatic diagnosis in dried blood spots on filter paper","volume":"308","author":"Chamoles","year":"2001","journal-title":"Clin. Chim. Acta"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/1750-1172-4-21","article-title":"Fabry disease: Recent advances in pathology, diagnosis, treatment and monitoring","volume":"4","author":"Hoffmann","year":"2009","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1007\/s10545-005-0039-4","article-title":"The ratio of alpha-galactosidase to beta-glucuronidase activities in dried blood for the identification of female Fabry disease patients","volume":"28","author":"Lukacs","year":"2005","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1373\/clinchem.2008.104711","article-title":"Multiplex Enzyme Assay Screening of Dried Blood Spots for Lysosomal Storage Disorders by Using Tandem Mass Spectrometry","volume":"54","author":"Zhang","year":"2008","journal-title":"Clin. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.1373\/clinchem.2004.037937","article-title":"Immunoquantification of \u03b1-Galactosidase: Evaluation for the Diagnosis of Fabry Disease","volume":"50","author":"Fuller","year":"2004","journal-title":"Clin. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1373\/clinchem.2004.035907","article-title":"Direct Multiplex Assay of Lysosomal Enzymes in Dried Blood Spots for Newborn Screening","volume":"50","author":"Li","year":"2004","journal-title":"Clin. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.cccn.2004.10.019","article-title":"Screening for Fabry disease using whole blood spots fails to identify one-third of female carriers","volume":"353","author":"Linthorst","year":"2005","journal-title":"Clin. Chim. Acta"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1542\/peds.2004-0583","article-title":"Newborn Screening for Lysosomal Storage Disorders: Clinical Evaluation of a Two-Tier Strategy","volume":"114","author":"Meikle","year":"2004","journal-title":"Pediatrics"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1006\/abio.1999.4002","article-title":"Determination of Urinary Sulfatides and Other Lipids by Combination of Reversed-Phase and Thin-Layer Chromatographies","volume":"269","author":"Berna","year":"1999","journal-title":"Anal. Biochem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/S0022-2275(20)38884-2","article-title":"Quantitative determination of the neutral glycosyl ceramides in human blood","volume":"8","author":"Vance","year":"1967","journal-title":"J. Lipid Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1093\/chromsci\/41.3.142","article-title":"Separation and Determination of Phospholipids in Biological Samples by High-Performance Liquid Chromatography","volume":"41","author":"Wang","year":"2003","journal-title":"J. Chromatogr. Sci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.1161\/CIRCULATIONAHA.108.841494","article-title":"Cardiac microvascular pathology in Fabry disease: Evaluation of endomyocardial biopsies before and after enzyme replacement therapy","volume":"119","author":"Thurberg","year":"2009","journal-title":"Circulation"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Monda, E., and Limongelli, G. (2022). Is There a Role for Genetic Testing in Patients With Myocarditis?. Circ. Genom. Precis. Med., In Press.","DOI":"10.1161\/CIRCGEN.122.003824"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1177\/2047487320934265","article-title":"Yield and clinical significance of genetic screening in elite and amateur athletes","volume":"28","author":"Limongelli","year":"2020","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"632293","DOI":"10.3389\/fped.2021.632293","article-title":"Hypertrophic Cardiomyopathy in Children: Pathophysiology, Diagnosis, and Treatment of Non-sarcomeric Causes","volume":"9","author":"Monda","year":"2021","journal-title":"Front. Pediatr."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1177\/2047487320940863","article-title":"Unexplained sudden cardiac arrest in children: Clinical and genetic characteristics of survivors","volume":"28","author":"Monda","year":"2020","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_93","first-page":"1186","article-title":"Nature and frequency of mutations in the al-pha-galactosidase A gene that cause Fabry disease","volume":"53","author":"Eng","year":"1993","journal-title":"Am. J. Hum. Genet."},{"key":"ref_94","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_95","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_96","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_97","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1038\/ncpcardio1012","article-title":"Cardiac Fabry\u2019s disease: An unusual cause of left ventricular hypertrophy","volume":"4","author":"Nunes","year":"2007","journal-title":"Nat. Clin. Pract. Cardiovasc. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1086\/339431","article-title":"Alternative Splicing in the \u03b1-Galactosidase A Gene: Increased Exon Inclusion Results in the Fabry Cardiac Phenotype","volume":"70","author":"Ishii","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"9319","DOI":"10.1016\/S0021-9258(19)38851-9","article-title":"Alpha-galactosidase A gene rearrangements causing Fabry disease. Identification of short direct repeats at breakpoints in an Alu-rich gene","volume":"265","author":"Kornreich","year":"1990","journal-title":"J. Biol. Chem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1002\/humu.20144","article-title":"Detection of \u03b1-galactosidase a mutations causing Fabry disease by denaturing high performance liquid chromatography","volume":"25","author":"Shabbeer","year":"2005","journal-title":"Hum. Mutat."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"e002839","DOI":"10.1161\/JAHA.115.002839","article-title":"High-Sensitivity Troponin: A Clinical Blood Biomarker for Staging Cardiomyopathy in Fabry Disease","volume":"5","author":"Seydelmann","year":"2016","journal-title":"J. Am. Heart Assoc."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.ymgme.2011.06.021","article-title":"Cystatin C and NT-proBNP as prognostic biomarkers in Fabry disease","volume":"104","author":"Olivera","year":"2011","journal-title":"Mol. Genet. Metab."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2812","DOI":"10.1073\/pnas.0712309105","article-title":"Elevated globotriaosylsphingosine is a hallmark of Fabry disease","volume":"105","author":"Aerts","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_104","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 diseas","volume":"59","author":"Nowak","year":"2022","journal-title":"J. Med. Genet."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1007\/s10545-010-9261-9","article-title":"Toward a consensus in the laboratory diagnostics of Fabry disease\u2014Recommendations of a European expert group","volume":"34","author":"Gal","year":"2011","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_106","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_107","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13052-016-0320-1","article-title":"Metabolic progression to clinical phenotype in classic Fabry disease","volume":"43","author":"Spada","year":"2017","journal-title":"Ital. J. Pediatr."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Gambardella, J., Fiordelisi, A., Sorriento, D., Cerasuolo, F., Buonaiuto, A., Avvisato, R., Pisani, A., Varzideh, F., Riccio, E., and Santulli, G. (2022). Mitochondrial microRNAs are dysregulated in patients with Fabry Disease. J. Pharmacol. Exp. Ther., In Press.","DOI":"10.1124\/jpet.122.001250"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-Pereira, C., Mill\u00e1n-Tejado, B.S., Gallardo-G\u00f3mez, M., P\u00e9rez-M\u00e1rquez, T., Alves-Villar, M., Melc\u00f3n-Crespo, C., Fern\u00e1ndez-Mart\u00edn, J., and Ortolano, S. (2021). Therapeutic Approaches in Lysosomal Storage Diseases. Biomolecules, 11.","DOI":"10.3390\/biom11121775"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1136\/hrt.2006.104026","article-title":"Effects of enzyme replacement therapy on the cardiomyopathy of Anderson-Fabry disease: A randomised, double-blind, placebo-controlled clinical trial of agalsidase alfa","volume":"94","author":"Hughes","year":"2008","journal-title":"Heart"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"77","DOI":"10.7326\/0003-4819-146-2-200701160-00148","article-title":"Agalsidase-beta therapy for advanced Fabry disease: A randomized trial","volume":"146","author":"Banikazemi","year":"2007","journal-title":"Ann. Intern. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"100454","DOI":"10.1016\/j.ymgmr.2019.100454","article-title":"The effect of enzyme replacement therapy on clinical outcomes in male patients with Fabry disease: A systematic literature review by a European panel of experts","volume":"19","author":"Germain","year":"2019","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1136\/jmedgenet-2014-102797","article-title":"Ten-year outcome of enzyme replacement therapy with agalsidase beta in patients with Fabry disease","volume":"52","author":"Germain","year":"2015","journal-title":"J. Med. Genet."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.ymgme.2008.10.004","article-title":"A retrospective analysis of the potential impact of IgG antibodies to agalsidase beta on efficacy during enzyme replacement therapy for Fabry disease","volume":"96","author":"Goyal","year":"2009","journal-title":"Mol. Genet. Metab."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1002\/jimd.12228","article-title":"Developments in the treatment of Fabry disease","volume":"43","author":"Hollak","year":"2020","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_116","first-page":"S111","article-title":"Pharmacological chaperone therapy by active-site-specific chaperones in Fabry disease: In vitro and preclinical studies","volume":"47","author":"Germain","year":"2009","journal-title":"Int. J. Clin. Pharmacol. Ther."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1136\/heartjnl-2014-306782","article-title":"Clinical and genetic predictors of major cardiac events in patients with Anderson\u2013Fabry Disease","volume":"101","author":"Patel","year":"2015","journal-title":"Heart"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1016\/j.jacc.2022.06.027","article-title":"A Roadmap to Predict Adverse Outcome in Fabry Disease","volume":"80","author":"Monda","year":"2022","journal-title":"J. Am. Coll. Cardiol."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/10\/1460\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:50:26Z","timestamp":1760143826000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/10\/1460"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,12]]},"references-count":118,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["biom12101460"],"URL":"https:\/\/doi.org\/10.3390\/biom12101460","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,12]]}}}