BACKGROUND: Family genetic testing of patients newly diagnosed with a rare genetic disease can improve early diagnosis of family members, allowing patients to receive disease-specific therapies when available. Fabry disease, an X-linked lysosomal storage disorder caused by pathogenic variants in GLA, can lead to end-stage renal disease, cardiac arrhythmias, and stroke. Diagnostic delays are common due to the rarity of the disease and non-specificity of early symptoms. Newborn screening and screening of at-risk populations, (e.g., patients with hypertrophic cardiomyopathy or undiagnosed nephropathies) can identify individuals with Fabry disease. Subsequent cascade genotyping of family members may disclose a greater number of affected individuals, often at younger age than they would have been diagnosed otherwise. METHODS: We conducted a literature search to identify all published data on family genetic testing for Fabry disease, and discussed these data, experts' own experiences with family genetic testing, and the barriers to this type of screening that are present in their respective countries. RESULTS: There are potential barriers that make implementation of family genetic testing challenging in some countries. These include associated costs and low awareness of its importance, and cultural and societal issues. Regionally, there are barriers associated with population educational levels, national geography and infrastructures, and a lack of medical geneticists. CONCLUSION: In this review, the worldwide experience of an international group of experts of Fabry disease highlights the issues faced in the family genetic testing of patients affected with rare genetic diseases.

1st Faculty of Medicine Charles University Prague Czech Republic

Center for Rare Diseases and Newborn Screening Vietnam National Children's Hospital Hanoi Vietnam

Centre Hospitalo Universitaire Mustapha Algiers Algeria

Department of Nephrology Institute of Nephrology Ruijin Hospital The Medical School of Shanghai Jiao Tong University Shanghai China

Department of Neurology Chang Gung Memorial Hospital Linkou Medical Center Taoyuan Taiwan

Department of Pediatric Genetics Amrita Institute of Medical Sciences and Research Centre Kochi India

Department of Pediatrics Taipei Veterans General Hospital Taipei Taiwan

Faculty of Medicine University of Puthisastra Phnom Penh Cambodia

French Referral Center for Fabry disease Division of Medical Genetics University of Versailles Montigny France

Genetic Unit Shaare Zedek Medical Center Jerusalem Israel

Hospital Español México City Mexico

Institute of Clinical Medicine National Yang Ming University Taipei Taiwan

Instituto de Genética Humana Facultad de Medicina Pontificia Universidad Javeriana and Servicio de Genética Hospital Universitario San Ignacio Bogotá Colombia

MCH Hospital Al Hassa Saudi Arabia

Medical Genetics Department Atieh Hospital Tehran Iran

MetabERN Center for Rare Diseases APHP Paris Saclay University Paris France

Nephrology Department The Royal Hospital Muscat Oman

Neurology Department Laboratorio Neuroquímica Dr Néstor Chamoles Buenos Aires Buenos Aires Argentina

Research Centre for Medical Genetics Moscow Russia

Sanofi Moscow Russia

Service of Nephrology Department of Internal Medicine Federal University of Paraná Curitiba Brazil

Tareev Clinic of Internal Diseases Sechenov 1st Moscow State Medical University Moscow Russia

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Adalsteinsdottir, B. , Palsson, R. , Desnick, R. J. , Gardarsdottir, M. , Teekakirikul, P. , Maron, M. , Appelbaum, E. , Neisius, U. , Maron, B. J. , Burke, M. A. , Chen, B. , Pagant, S. , Madsen, C. V. , Danielsen, R. , Arngrimsson, R. , Feldt‐Rasmussen, U. , Seidman, J. G. , Seidman, C. E. , & Gunnarsson, G. T. (2017). Fabry disease in families with hypertrophic cardiomyopathy: Clinical manifestations in the classic and later‐onset phenotypes. Circulation. Cardiovascular Genetics, 10, e001639. 10.1161/CIRCGENETICS.116.001639 PubMed DOI

Auray‐Blais, C. , Blais, C. M. , Ramaswami, U. , Boutin, M. , Germain, D. P. , Dyack, S. , Bodamer, O. , Pintos‐Morell, G. , Clarke, J. T. , Bichet, D. G. , Warnock, D. G. , Echevarria, L. , West, M. L. , & Lavoie, P. (2015). Urinary biomarker investigation in children with Fabry disease using tandem mass spectrometry. Clinica Chimica Acta, 438, 195–204. 10.1016/j.cca.2014.08.002 PubMed DOI

Azevedo, O. , Gal, A. , Faria, R. , Gaspar, P. , Miltenberger‐Miltenyi, G. , Gago, M. F. , Dias, F. , Martins, A. , Rodrigues, J. , Reimão, P. , Pereira, O. , Simões, S. , Lopes, E. , Guimarães, M. J. , Sousa, N. , & Cunha, D. (2020). Founder effect of Fabry disease due to p. F113L mutation: Clinical profile of a late‐onset phenotype. Molecular Genetics and Metabolism, 129, 150–160. 10.1016/j.ymgme.2019.07.012 PubMed DOI

Barman, H. A. , Özcan, S. , Atıcı, A. , Özgökçe, C. , Öztürk, A. , Kafalı, A. E. , Çakar, N. E. , Tavşanlı, M. E. , Küçük, M. , Şahin, I. , & Okuyan, E. (2020). Ratio of Fabry disease in patients with idiopathic left ventricular hypertrophy: A single‐center study in Turkey. Anatolian Journal of Cardiology, 23, 79–85. 10.14744/AnatolJCardiol.2019.84782 PubMed DOI PMC

Boutouyrie, P. , Laurent, S. , Laloux, B. , Lidove, O. , Grunfeld, J. P. , & Germain, D. P. (2002). Arterial remodelling in Fabry disease. Acta Paediatrica, 91, 62–66. 10.1111/j.1651-2227.2002.tb03113.x PubMed DOI

Burlina, A. B. , Polo, G. , Salviati, L. , Duro, G. , Zizzo, C. , Dardis, A. , Bembi, B. , Cazzorla, C. , Rubert, L. , Zordan, R. , Desnick, R. J. , & Burlina, A. P. (2018). Newborn screening for lysosomal storage disorders by tandem mass spectrometry in North East Italy. Journal of Inherited Metabolic Disease, 41, 209–219. 10.1007/s10545-017-0098-3 PubMed DOI

Chinen, Y. , Nakamura, S. , Yoshida, T. , Maruyama, H. , & Nakamura, K. (2017). A new mutation found in newborn screening for Fabry disease evaluated by plasma globotriaosylsphingosine levels. Human Genome Variation, 4, 17002. 10.1038/hgv.2017.2 PubMed DOI PMC

Choi, J. H. , Lee, B. H. , Heo, S. H. , Kim, G. H. , Kim, Y. M. , Kim, D. S. , Ko, J. M. , Sohn, Y. B. , Hong, Y. H. , Lee, D. H. , Kook, H. , Lim, H. H. , Kim, K. H. , Kim, W. S. , Hong, G. R. , Kim, S. H. , Park, S. H. , Kim, C. D. , Kim, S. M. , Seo, J. S. , & Yoo, H. W. (2017). Clinical characteristics and mutation spectrum of GLA in Korean patients with Fabry disease by a nationwide survey: Underdiagnosis of late‐onset phenotype. Medicine, 96, e7387. 10.1097/MD.0000000000007387 PubMed DOI PMC

De Brabander, I. , Yperzeele, L. , Ceuterick‐De Groote, C. , Brouns, R. , Baker, R. , Belachew, S. , Delbecq, J. , De Keulenaer, G. , Dethy, S. , Eyskens, F. , Fumal, A. , Hemelsoet, D. , Hughes, D. , Jeangette, S. , Nuytten, D. , Redondo, P. , Sadzot, B. , Sindic, C. , Sheorajpanday, R. , & De Deyn, P. P. (2013). Phenotypical characterization of α‐galactosidase A gene mutations identified in a large Fabry disease screening program in stroke in the young. Clinical Neurology and Neurosurgery, 115, 1088–1093. 10.1016/j.clineuro.2012.11.003 PubMed DOI

Desnick, R. J. , Brady, R. , Barranger, J. , Collins, A. J. , Germain, D. P. , Goldman, M. , Grabowski, G. , Packman, S. , & Wilcox, W. R. (2003). Fabry disease, an under‐recognized multisystemic disorder: Expert recommendations for diagnosis, management, and enzyme replacement therapy. Annals of Internal Medicine, 138, 338–346. 10.7326/0003-4819-138-4-200302180-00014 PubMed DOI

Dobrovolný, R. , Dvoráková, L. , Ledvinová, J. , Magage, S. , Bultas, J. , Lubanda, J. C. , Poupetová, H. , Elleder, M. , Karetová, D. , & Hrebícek, M. (2005). Recurrence of Fabry disease as a result of paternal germline mosaicism for alpha‐galactosidase a gene mutation. American Journal of Medical Genetics. Part A, 134A, 84–87. 10.1002/ajmg.a.30533 PubMed DOI

Doheny, D. , Srinivasan, R. , Pagant, S. , Chen, B. , Yasuda, M. , & Desnick, R. J. (2018). Fabry disease: Prevalence of affected males and heterozygotes with pathogenic GLA mutations identified by screening renal, cardiac and stroke clinics, 1995–2017. Journal of Medical Genetics, 55, 261–268. 10.1136/jmedgenet-2017-105080 PubMed DOI

Echevarria, L. , Benistan, K. , Toussaint, A. , Dubourg, O. , Hagege, A. A. , Eladari, D. , Jabbour, F. , Beldjord, C. , De Mazancourt, P. , & Germain, D. P. (2016). X‐chromosome inactivation in female patients with Fabry disease. Clinical Genetics, 89, 44–54. 10.1111/cge.12613 PubMed DOI

Eng, C. M. , Guffon, N. , Wilcox, W. R. , Germain, D. P. , Lee, P. , Waldek, S. , Caplan, L. , Linthorst, G. E. , Desnick, R. J. , & International Collaborative Fabry Disease Study Group . (2001). Safety and efficacy of recombinant human alpha‐galactosidase A replacement therapy in Fabry's disease. The New England Journal of Medicine, 345, 9–16. 10.1056/NEJM200107053450102 PubMed DOI

Eng, C. M. , Resnick‐Silverman, L. A. , Niehaus, D. J. , Astrin, K. H. , & Desnick, R. J. (1993). Nature and frequency of mutations in the alpha‐galactosidase A gene that cause Fabry disease. American Journal of Human Genetics, 53, 1186–1197. PubMed PMC

Feriozzi, S. , Torre, E. S. , Ranalli, T. V. , Cardello, P. , Morrone, A. , & Ancarani, E. (2007). A diagnosis of Fabry gastrointestinal disease by chance: A case report. European Journal of Gastroenterology & Hepatology, 19, 163–165. 10.1097/MEG.0b013e32800fef46 PubMed DOI

Ferreira, S. , Ortiz, A. , Germain, D. P. , Viana‐Baptista, M. , Caldeira‐Gomes, A. , Camprecios, M. , Fenollar‐Cortés, M. , Gallegos‐Villalobos, Á. , Garcia, D. , García‐Robles, J. A. , Egido, J. , Gutiérrez‐Rivas, E. , Herrero, J. A. , Mas, S. , Oancea, R. , Péres, P. , Salazar‐Martín, L. M. , Solera‐Garcia, J. , Alves, H. , Garman, S. C. , & Oliveira, J. P. (2015). The alpha‐galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: Data from individual patients and family studies. Molecular Genetics and Metabolism, 114, 248–258. 10.1016/j.ymgme.2014.11.004 PubMed DOI PMC

Gabrielli, O. , Clarke, L. A. , Ficcadenti, A. , Santoro, L. , Zampini, L. , Volpi, N. , & Coppa, G. V. (2016). 12 year follow up of enzyme‐replacement therapy in two siblings with attenuated mucopolysaccharidosis I: The important role of early treatment. BMC Medical Genetics, 17, 19. 10.1186/s12881-016-0284-4 PubMed DOI PMC

Gal, A. , Beck, M. , Höppner, W. , & Germain, D. P. (2017). Clinical utility gene card for: Fabry disease – update 2016. European Journal of Human Genetics, 25, e1–e3. 10.1038/ejhg.2017.1 PubMed DOI PMC

Germain, D. P. (2001). A new phenotype of Fabry disease with intermediate severity between the classical form and the cardiac variant. Contribution in Nephrology, 136, 234–240. PubMed

Germain, D. P. (2010). Fabry disease. Orphanet Journal of Rare Diseases, 5, 30. 10.1186/1750-1172-5-30 PubMed DOI PMC

Germain, D. P. , Arad, M. , Burlina, A. , Elliott, P. M. , Falissard, B. , Feldt‐Rasmussen, U. , Hilz, M. J. , Hughes, D. A. , Ortiz, A. , Wanner, C. , Weidemann, F. , & Spada, M. (2019). The effect of enzyme replacement therapy on clinical outcomes in female patients with Fabry disease – A systematic literature review by a European panel of experts. Molecular Genetics and Metabolism, 126, 224–235. 10.1016/j.ymgme.2018.09.007 PubMed DOI

Germain, D. P. , Biasotto, M. , Tosi, M. , Meo, T. , Kahn, A. , & Poenaru, L. (1996). Fluorescence‐assisted mismatch analysis (FAMA) for exhaustive screening of the alpha‐galactosidase A gene and detection of carriers in Fabry disease. Human Genetics, 98, 719–726. 10.1007/s004390050292 PubMed DOI

Germain, D. P. , Brand, E. , Burlina, A. , Cecchi, F. , Garman, S. C. , Kempf, J. , Laney, D. A. , Linhart, A. , Maródi, L. , Nicholls, K. , Ortiz, A. , Pieruzzi, F. , Shankar, S. P. , Waldek, S. , Wanner, C. , & Jovanovic, A. (2018). Phenotypic characteristics of the p.Asn215Ser (p. N215S) GLA mutation in male and female patients with Fabry disease: A multicenter Fabry Registry study. Molecular Genetics & Genomic Medicine, 6, 492–503. 10.1002/mgg3.389 PubMed DOI PMC

Germain, D. P. , Charrow, J. , Desnick, R. J. , Guffon, N. , Kempf, J. , Lachmann, R. H. , Lemay, R. , Linthorst, G. E. , Packman, S. , Scott, C. R. , Waldek, S. , Warnock, D. G. , Weinreb, N. J. , & Wilcox, W. R. (2015). Ten‐year outcome of enzyme replacement therapy with agalsidase beta in patients with Fabry disease. Journal of Medical Genetics, 52, 353–358. 10.1136/jmedgenet-2014-102797 PubMed DOI PMC

Germain, D. P. , Elliott, P. M. , Falissard, B. , Fomin, V. V. , Hilz, M. J. , Jovanovic, A. , Kantola, I. , Linhart, A. , Mignani, R. , Namdar, M. , Nowak, A. , Oliveira, J. P. , Pieroni, M. , Viana‐Baptista, M. , Wanner, C. , & Spada, M. (2019). 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. Molecular Genetics and Metabolism Reports, 19, 100454. 10.1016/j.ymgmr.2019.100454 PubMed DOI PMC

Germain, D. P. , & Fan, J. Q. (2009). Pharmacological chaperone therapy by active‐site‐specific chaperones in Fabry disease: In vitro and preclinical studies. International Journal of Clinical Pharmacology and Therapeutics, 47, S111–S117. PubMed

Germain, D. P. , Fouilhoux, A. , Decramer, S. , Tardieu, M. , Pillet, P. , Fila, M. , Rivera, S. , Deschênes, G. , & Lacombe, D. (2019). Consensus recommendations for diagnosis, management and treatment of Fabry disease in paediatric patients. Clinical Genetics, 96, 107–117. 10.1111/cge.13546 PubMed DOI PMC

Germain, D. P. , Hughes, D. A. , Nicholls, K. , Bichet, D. G. , Giugliani, R. , Wilcox, W. R. , Feliciani, C. , Shankar, S. P. , Ezgu, F. , Amartino, H. , Bratkovic, D. , Feldt‐Rasmussen, U. , Nedd, K. , Sharaf El Din, U. , Lourenco, C. M. , Banikazemi, M. , Charrow, J. , Dasouki, M. , Finegold, D. , & Schiffmann, R. (2016). Treatment of Fabry's disease with the pharmacologic chaperone migalastat. The New England Journal of Medicine, 375, 545–555. 10.1056/NEJMoa1510198 PubMed DOI

Germain, D. P. , & Jurca‐Simina, I. E. (2018). Principles of human genetics and Mendelian inheritance. In Burlina A. P. (Ed.), Neurometabolic hereditary diseases of adults (pp. 1–28). Springer.

Germain, D. P. , Oliveira, J. P. , Bichet, D. G. , Yoo, H. W. , Hopkin, R. J. , Lemay, R. , Politei, J. , Wanner, C. , Wilcox, W. R. , & Warnock, D. G. (2020). 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‐phenotype workgroup. Journal of Medical Genetics, 57, 542–551. 10.1136/jmedgenet-2019-106467 PubMed DOI PMC

Germain, D. P. , & Poenaru, L. (1999). Fabry disease: Identification of novel alpha‐galactosidase A mutations and molecular carrier detection by use of fluorescent chemical cleavage of mismatches. Biochemical and Biophysical Research Communications, 257, 708–713. 10.1006/bbrc.1999.0310 PubMed DOI

Hagège, A. A. , Caudron, E. , Damy, T. , Roudaut, R. , Millaire, A. , Etchecopar‐Chevreuil, C. , Tran, T. C. , Jabbour, F. , Boucly, C. , Prognon, P. , Charron, P. , Germain, D. P. , & FOCUS study investigators . (2011). Screening patients with hypertrophic cardiomyopathy for Fabry disease using a filter‐paper test: The FOCUS study. Heart, 97, 131–136. 10.1136/hrt.2010.200188 PubMed DOI

Hagège, A. , Réant, P. , Habib, G. , Damy, T. , Barone‐Rochette, G. , Soulat, G. , Donal, E. , & Germain, D. P. (2019). Fabry disease in cardiology practice: Literature review and expert point of view. Archives of Cardiovascular Diseases, 112, 278–287. 10.1016/j.acvd.2019.01.002 PubMed DOI

Hopkin, R. J. , Bissler, J. , Banikazemi, M. , Clarke, L. , Eng, C. M. , Germain, D. P. , Lemay, R. , Tylki‐Szymanska, A. , & Wilcox, W. R. (2008). Characterization of Fabry disease in 352 pediatric patients in the Fabry Registry. Pediatric Research, 64, 550–555. 10.1203/PDR.0b013e318183f132 PubMed DOI

Hopkin, R. J. , Jefferies, J. L. , Laney, D. A. , Lawson, V. H. , Mauer, M. , Taylor, M. R. , & Wilcox, W. R. (2016). The management and treatment of children with Fabry disease: A United States‐based perspective. Molecular Genetics and Metabolism, 117, 104–113. 10.1016/j.ymgme.2015.10.007 PubMed DOI

Hsu, T. R. , Hung, S. C. , Chang, F. P. , Yu, W. C. , Sung, S. H. , Hsu, C. L. , Dzhagalov, I. , Yang, C. F. , Chu, T. H. , Lee, H. J. , Lu, Y. H. , Chang, S. K. , Liao, H. C. , Lin, H. Y. , Liao, T. C. , Lee, P. C. , Li, H. Y. , Yang, A. H. , Ho, H. C. , & Niu, D. M. (2016). Later onset Fabry disease, cardiac damage progress in silence: Experience with a highly prevalent mutation. Journal of the American College of Cardiology, 68, 2554–2563. 10.1016/j.jacc.2016.09.943 PubMed DOI

Ishii, S. , Nakao, S. , Minamikawa‐Tachino, R. , Desnick, R. J. , & Fan, J. Q. (2002). Alternative splicing in the alpha‐galactosidase A gene: Increased exon inclusion results in the Fabry cardiac phenotype. American Journal of Human Genetics, 70, 994–1002. 10.1086/339431 PubMed DOI PMC

Kolodny, E. , Fellgiebel, A. , Hilz, M. J. , Sims, K. , Caruso, P. , Phan, T. G. , Politei, J. , Manara, R. , & Burlina, A. (2015). Cerebrovascular involvement in Fabry disease: Current status of knowledge. Stroke, 46, 302–313. 10.1161/STROKEAHA.114.006283 PubMed DOI

Laney, D. A. , & Fernhoff, P. M. (2008). Diagnosis of Fabry disease via analysis of family history. Journal of Genetic Counseling, 17, 79–83. 10.1007/s10897-007-9128-x PubMed DOI

Laney, D. A. , Germain, D. P. , Oliveira, J. P. , Burlina, A. P. , Cabrera, G. H. , Hong, G. R. , Hopkin, R. J. , Niu, D. M. , Thomas, M. , Trimarchi, H. , Wilcox, W. R. , Politei, J. M. , & Ortiz, A. (2020). Fabry disease and COVID‐19: International expert recommendations for management based on real‐world experience. Clinical Kidney Journal, 13, 913–925. 10.1093/ckj/sfaa227 PubMed DOI PMC

Liao, H. C. , Hsu, T. R. , Young, L. , Chiang, C. C. , Huang, C. K. , Liu, H. C. , Niu, D. M. , & Chen, Y. J. (2018). Functional and biological studies of α‐galactosidase A variants with uncertain significance from newborn screening in Taiwan. Molecular Genetics and Metabolism, 123, 140–147. 10.1016/j.ymgme.2017.06.002 PubMed DOI

Lin, C. J. , Chien, Y. H. , Lai, T. S. , Shih, H. M. , Chen, Y. C. , Pan, C. F. , Chen, H. H. , Hwu, W. L. , & Wu, C. J. (2018). Results of Fabry disease screening in male pre‐end stage renal disease patients with unknown etiology found through the platform of a chronic kidney disease education program in a northern Taiwan medical center. Kidney & Blood Pressure Research, 43, 1636–1645. 10.1159/000494678 PubMed DOI

Linhart, A. , Germain, D. P. , Olivotto, I. , Akhtar, M. M. , Anastasakis, A. , Hughes, D. , Namdar, M. , Pieroni, M. , Hagège, A. , Cecchi, F. , Gimeno, J. R. , Limongelli, G. , & Elliott, P. (2020). An expert consensus document on the management of cardiovascular manifestations of Fabry disease. European Journal of Heart Failure, 22, 1076–1096. 10.1002/ejhf.1960 PubMed DOI

Lv, Y. L. , Wang, W. M. , Pan, X. X. , Wang, Z. H. , Chen, N. , Ye, Z. Y. , & Xu, J. (2009). A successful screening for Fabry disease in a Chinese dialysis patient population. Clinical Genetics, 76, 219–221. 10.1111/j.1399-0004.2009.01166.x PubMed DOI

Magage, S. , Lubanda, J. C. , Susa, Z. , Bultas, J. , Karetová, D. , Dobrovolný, R. , Hrebícek, M. , Germain, D. P. , & Linhart, A. (2007). Natural history of the respiratory involvement in Anderson‐Fabry disease. Journal of Inherited Metabolic Disease, 30, 790–799. 10.1007/s10545-007-0616-9 PubMed DOI

Maron, M. S. , Xin, W. , Sims, K. B. , Butler, R. , Haas, T. S. , Rowin, E. J. , Desnick, R. J. , & Maron, B. J. (2018). Identification of Fabry disease in a tertiary referral cohort of patients with hypertrophic cardiomyopathy. The American Journal of Medicine, 131, 200.e1–200.e8. 10.1016/j.amjmed.2017.09.010 PubMed DOI

Mehta, A. , Beck, M. , Eyskens, F. , Feliciani, C. , Kantola, I. , Ramaswami, U. , Rolfs, A. , Rivera, A. , Waldek, S. , & Germain, D. P. (2010). Fabry disease: A review of current management strategies. QJM, 103, 641–659. 10.1093/qjmed/hcq117 PubMed DOI

Merta, M. , Reiterova, J. , Ledvinova, J. , Poupetová, H. , Dobrovolny, R. , Rysavá, R. , Maixnerová, D. , Bultas, J. , Motán, J. , Slivkova, J. , Sobotova, D. , Smrzova, J. , & Tesar, V. (2007). A nationwide blood spot screening study for Fabry disease in the Czech Republic haemodialysis patient population. Nephrology, Dialysis, Transplantation, 22, 179–186. 10.1093/ndt/gfl528 PubMed DOI

Nakao, S. , Kodama, C. , Takenaka, T. , Tanaka, A. , Yasumoto, Y. , Yoshida, A. , Kanzaki, T. , Enriquez, A. L. , Eng, C. M. , Tanaka, H. , Tei, C. , & Desnick, R. J. (2003). Fabry disease: Detection of undiagnosed hemodialysis patients and identification of a "renal variant" phenotype. Kidney International, 64, 801–807. 10.1046/j.1523-1755.2003.00160.x PubMed DOI

Nakao, S. , Takenaka, T. , Maeda, M. , Kodama, C. , Tanaka, A. , Tahara, M. , Yoshida, A. , Kuriyama, M. , Hayashibe, H. , Sakuraba, H. , & Tanaka, H. (1995). An atypical variant of Fabry's disease in men with left ventricular hypertrophy. The New England Journal of Medicine, 333, 288–293. 10.1056/NEJM199508033330504 PubMed DOI

Namdar, M. (2016). Electrocardiographic changes and arrhythmia in Fabry disease. Frontiers in Cardiovascular Medicine, 3, 7. 10.3389/fcvm.2016.00007 PubMed DOI PMC

Okur, I. , Ezgu, F. , Biberoglu, G. , Tumer, L. , Erten, Y. , Isitman, M. , Eminoglu, F. T. , & Hasanoglu, A. (2013). Screening for Fabry disease in patients undergoing dialysis for chronic renal failure in Turkey: Identification of new case with novel mutation. Gene, 527, 42–47. 10.1016/j.gene.2013.05.050 PubMed DOI

Oliveira, J. P. , Nowak, A. , Barbey, F. , Torres, M. , Nunes, J. P. , Teixeira‐e‐Costa, F. , Carvalho, F. , Sampaio, S. , Tavares, I. , Pereira, O. , Soares, A. L. , Carmona, C. , Cardoso, M. T. , Jurca‐Simina, I. E. , Spada, M. , Ferreira, S. , & Germain, D. P. (2020). Fabry disease caused by the GLA p.Phe113Leu (p.F113L) variant: Natural history in males. European Journal of Medical Genetics, 63, 103703. 10.1016/j.ejmg.2019.103703 PubMed DOI

Ortiz, A. , Abiose, A. , Bichet, D. G. , Cabrera, G. , Charrow, J. , Germain, D. P. , Hopkin, R. J. , Jovanovic, A. , Linhart, A. , Maruti, S. S. , Mauer, M. , Oliveira, J. P. , Patel, M. R. , Politei, J. , Waldek, S. , Wanner, C. , Yoo, H. W. , & Warnock, D. G. (2016). Time to treatment benefit for adult patients with Fabry disease receiving agalsidase β: Data from the Fabry Registry. Journal of Medical Genetics, 53, 495–502. 10.1136/jmedgenet-2015-103486 PubMed DOI PMC

Ortiz, A. , Cianciaruso, B. , Cizmarik, M. , Germain, D. P. , Mignani, R. , Oliveira, J. P. , Villalobos, J. , Vujkovac, B. , Waldek, S. , Wanner, C. , & Warnock, D. G. (2010). End‐stage renal disease in patients with Fabry disease: Natural history data from the Fabry Registry. Nephrology, Dialysis, Transplantation, 25, 769–775. 10.1093/ndt/gfp554 PubMed DOI

Ortiz, A. , Germain, D. P. , Desnick, R. J. , Politei, J. , Mauer, M. , Burlina, A. , Eng, C. , Hopkin, R. J. , Laney, D. , Linhart, A. , Waldek, S. , Wallace, E. , Weidemann, F. , & Wilcox, W. R. (2018). Fabry disease revisited: Management and treatment recommendations for adult patients. Molecular Genetics and Metabolism, 123, 416–427. 10.1016/j.ymgme.2018.02.014 PubMed DOI

Pettazzoni, M. , Froissart, R. , Pagan, C. , Vanier, M. T. , Ruet, S. , Latour, P. , Guffon, N. , Fouilhoux, A. , Germain, D. P. , Levade, T. , Vianey‐Saban, C. , Piraud, M. , & Cheillan, D. (2017). LC‐MS/MS multiplex analysis of lysosphingolipids in plasma and amniotic fluid: A novel tool for the screening of sphingolipidoses and Niemann‐Pick type C disease. PLoS One, 12, e0181700. 10.1371/journal.pone.0181700 PubMed DOI PMC

Politei, J. M. , Bouhassira, D. , Germain, D. P. , Goizet, C. , Guerrero‐Sola, A. , Hilz, M. J. , Hutton, E. J. , Karaa, A. , Liguori, R. , Üçeyler, N. , Zeltzer, L. K. , & Burlina, A. (2016). Pain in Fabry disease: Practical recommendations for diagnosis and treatment. CNS Neuroscience & Therapeutics, 22, 568–576. 10.1111/cns.12542 PubMed DOI PMC

Rajab, A. , Al Rashdi, I. , & Al Salmi, Q. (2013). Genetic services and testing in the Sultanate of Oman. Sultanate of Oman steps into modern genetics. Journal of Community Genetics, 4, 391–397. 10.1007/s12687-013-0153-1 PubMed DOI PMC

Reisin, R. , Perrin, A. , & García‐Pavía, P. (2017). Time delays in the diagnosis and treatment of Fabry disease. International Journal of Clinical Practice, 71, 12914. 10.1111/ijcp.12914 PubMed DOI

Richards, S. , Aziz, N. , Bale, S. , Bick, D. , Das, S. , Gastier‐Foster, J. , Grody, W. W. , Hegde, M. , Lyon, E. , Spector, E. , Voelkerding, K. , Rehm, H. L. , & ACMG Laboratory Quality Assurance Committee (2015). 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. Genetics in Medicine, 17, 405–424. 10.1038/gim.2015.30 PubMed DOI PMC

Rost, N. S. , Cloonan, L. , Kanakis, A. S. , Fitzpatrick, K. M. , Azzariti, D. R. , Clarke, V. , Lourenco, C. M. , Germain, D. P. , Politei, J. M. , Homola, G. A. , Sommer, C. , Üçeyler, N. , & Sims, K. B. (2016). Determinants of white matter hyperintensity burden in patients with Fabry disease. Neurology, 17, 1880–1886. 10.1212/WNL.0000000000002673 PubMed DOI PMC

Rozenfeld, P. A. , Masllorens, F. M. , Roa, N. , Rodriguez, F. , Bonnano, M. , Yvorra, C. , & Ceci, R. (2019). Fabry pedigree analysis: A successful program for targeted genetic approach. Molecular Genetics & Genomic Medicine, 7, e00794. 10.1002/mgg3.794 PubMed DOI PMC

Russo, C. , Riccio, E. , Pontillo, G. , Cocozza, S. , Tedeschi, E. , Centonze, D. , & Pisani, A. (2018). Multiple sclerosis and Fabry disease, two sides of the coin? The case of an Italian family. Multiple Sclerosis and Related Disorders, 26, 164–167. 10.1016/j.msard.2018.09.019 PubMed DOI

Sachdev, B. , Takenaka, T. , Teraguchi, H. , Tei, C. , Lee, P. , McKenna, W. J. , & Elliott, P. M. (2002). Prevalence of Anderson‐Fabry disease in male patients with late onset hypertrophic cardiomyopathy. Circulation, 105, 1407–1411. 10.1161/01.CIR.0000012626.81324.38 PubMed DOI

Schiffmann, R. , Hughes, D. A. , Linthorst, G. E. , Ortiz, A. , Svarstad, E. , Warnock, D. G. , West, M. L. , Wanner, C. , Bichet, D. G. , Christensen, E. I. , Correa‐Rotter, R. , Elliott, P. M. , Feriozzi, S. , Fogo, A. B. , Germain, D. P. , Hollak, C. E. M. , Hopkin, R. J. , Johnson, J. , Kantola, I. , & Walter, J. (2017). Screening, diagnosis, and management of patients with Fabry disease: Conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference. Kidney International, 91, 284–293. 10.1016/j.kint.2016.10.004 PubMed DOI

Schiffmann, R. , Kopp, J. B. , Austin, H. A. 3rd , Sabnis, S. , Moore, D. F. , Weibel, T. , Balow, J. E. , & Brady, R. O. (2001). Enzyme replacement therapy in Fabry disease: A randomized controlled trial. JAMA, 285, 2743–2749. 10.1001/jama.285.21.2743 PubMed DOI

Silva, C. A. , Barreto, F. C. , Dos Reis, M. A. , Moura Junior, J. A. , & Cruz, C. M. (2016). Targeted screening of Fabry disease in male hemodialysis patients in Brazil s importance of family screening. Nephron, 134, 221–230. 10.1159/000448740 PubMed DOI

Spada, M. , Pagliardini, S. , Yasuda, M. , Tukel, T. , Thiagarajan, G. , Sakuraba, H. , Ponzone, A. , & Desnick, R. J. (2006). High incidence of later‐onset Fabry disease revealed by newborn screening. American Journal of Human Genetics, 79, 31–40. 10.1086/504601 PubMed DOI PMC

Terryn, W. , Poppe, B. , Wuyts, B. , Claes, K. , Maes, B. , Verbeelen, D. , Vanholder, R. , De Boeck, K. , Lameire, N. , De Paepe, A. , & De Schoenmakere, G. (2008). Two‐tier approach for the detection of alpha‐galactosidase A deficiency in a predominantly female haemodialysis population. Nephrology, Dialysis, Transplantation, 23, 294–300. 10.1093/ndt/gfm532 PubMed DOI

Turkmen, K. , Guclu, A. , Sahin, G. , Kocyigit, I. , Demirtas, L. , Erdur, F. M. , Sengül, E. , Ozkan, O. , Emre, H. , Turgut, F. , Unal, H. , Karaman, M. , Acıkel, C. , Esen, H. , Balli, E. , Bıtırgen, G. , Tonbul, H. Z. , Yılmaz, M. I. , & Ortiz, A. (2016). The prevalence of Fabry disease in patients with chronic kidney disease in Turkey: The TURKFAB study. Kidney & Blood Pressure Research, 41, 1016–1024. 10.1159/000452605 PubMed DOI

van der Tol, L. , Smid, B. E. , Poorthuis, B. J. , Biegstraaten, M. , Deprez, R. H. , Linthorst, G. E. , & Hollak, C. E. (2014). A systematic review on screening for Fabry disease: Prevalence of individuals with genetic variants of unknown significance. Journal of Medical Genetics, 51, 1–9. 10.1136/jmedgenet-2013-101857 PubMed DOI

Varela, P. , Mastroianni Kirsztajn, G. , Motta, F. L. , Martin, R. P. , Turaça, L. T. , Ferrer, H. , Gomes, C. P. , Nicolicht, P. , Mara Marins, M. , Pessoa, J. G. , Braga, M. C. , D'Almeida, V. , Martins, A. M. , & Pesquero, J. B. (2020). Correlation between GLA variants and alpha‐Galactosidase A profile in dried blood spot: An observational study in Brazilian patients. Orphanet Journal of Rare Diseases, 15, 30. 10.1186/s13023-019-1274-3 PubMed DOI PMC

Veloso, V. , Ataides, T. L. , Canziani, M. , Veloso, M. P. , da Silva, N. A. , Barreto, D. V. , Pereira, E. , de Moura, L. , & Barreto, F. C. (2018). A novel missense GLA mutation (p. G35V) detected in hemodialysis screening leads to severe systemic manifestations of Fabry disease in men and women. Nephron, 138, 147–156. 10.1159/000479895 PubMed DOI

Wanner, C. , Arad, M. , Baron, R. , Burlina, A. , Elliott, P. M. , Feldt‐Rasmussen, U. , Fomin, V. V. , Germain, D. P. , Hughes, D. A. , Jovanovic, A. , Kantola, I. , Linhart, A. , Mignani, R. , Monserrat, L. , Namdar, M. , Nowak, A. , Oliveira, J.‐P. , Ortiz, A. , Pieroni, M. , & Hilz, M. J. (2018). European expert consensus statement on therapeutic goals in Fabry disease. Molecular Genetics and Metabolism, 124, 189–203. 10.1016/j.ymgme.2018.06.004 PubMed DOI

Warnock, D. G. , Ortiz, A. , Mauer, M. , Linthorst, G. E. , Oliveira, J. P. , Serra, A. L. , Maródi, L. , Mignani, R. , Vujkovac, B. , Beitner‐Johnson, D. , Lemay, R. , Cole, J. A. , Svarstad, E. , Waldek, S. , Germain, D. P. , Wanner, C. , & Fabry Registry (2012). Renal outcomes of agalsidase beta treatment for Fabry disease: Role of proteinuria and timing of treatment initiation. Nephrology, Dialysis, Transplantation, 27, 1042–1049. 10.1093/ndt/gfr420 PubMed DOI PMC

Wilcox, W. R. , Oliveira, J. P. , Hopkin, R. J. , Ortiz, A. , Banikazemi, M. , Feldt‐Rasmussen, U. , Sims, K. , Waldek, S. , Pastores, G. M. , Lee, P. , Eng, C. M. , Marodi, L. , Stanford, K. E. , Breunig, F. , Wanner, C. , Warnock, D. G. , Lemay, R. M. , Germain, D. P. , & Fabry Registry (2008). Females with Fabry disease frequently have major organ involvement: Lessons from the Fabry Registry. Molecular Genetics and Metabolism, 93, 112–128. 10.1016/j.ymgme.2007.09.013 PubMed DOI

Nationwide screening of Fabry disease in patients with hypertrophic cardiomyopathy in Czech Republic

The Benefits of Family Screening in Rare Diseases: Genetic Testing Reveals 165 New Cases of Fabry Disease among At-Risk Family Members of 83 Index Patients