title: Characterization of Classical and Nonclassical Fabry Disease: A Multicenter Study.
abstract: Fabry disease leads to renal, cardiac, and cerebrovascular manifestations. Phenotypic differences between classically and nonclassically affected patients are evident, but there are few data on the natural course of classical and nonclassical disease in men and women. To describe the natural course of Fabry disease stratified by sex and phenotype, we retrospectively assessed event-free survival from birth to the first clinical visit (before enzyme replacement therapy) in 499 adult patients (mean age 43 years old; 41% men; 57% with the classical phenotype) from three international centers of excellence. We classified patients by phenotype on the basis of characteristic symptoms and enzyme activity. Men and women with classical Fabry disease had higher event rate than did those with nonclassical disease (hazard ratio for men, 5.63, 95% confidence interval, 3.17 to 10.00;P<0.001; hazard ratio for women, 2.88, 95% confidence interval, 1.54 to 5.40;P<0.001). Furthermore, men with classical Fabry disease had lower eGFR, higher left ventricular mass, and higher plasma globotriaosylsphingosine concentrations than men with nonclassical Fabry disease or women with either phenotype (P<0.001). In conclusion, before treatment with enzyme replacement therapy, men with classical Fabry disease had a history of more events than men with nonclassical disease or women with either phenotype; women with classical Fabry disease were more likely to develop complications than women with nonclassical disease. These data may support the development of new guidelines for the monitoring and treatment of Fabry disease and studies on the effects of intervention in subgroups of patients.
authors.affiliation: Departments of Endocrinology and Metabolism and m.arends@amc.uva.nl.
authors.forename: Maarten
authors.initials: M
authors.lastname: Arends
authors.affiliation: Department of Internal Medicine I, Division of Cardiology and Nephrology, Comprehensive Heart Failure Center and Fabry Center for Interdisciplinary Therapy, University Hospital Wuerzburg, Wuerzburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wanner
authors.affiliation: Department of Haematology, Royal Free London National Health Service Foundation Trust and University College London, London, United Kingdom and.
authors.forename: Derralynn
authors.initials: D
authors.lastname: Hughes
authors.affiliation: Department of Haematology, Royal Free London National Health Service Foundation Trust and University College London, London, United Kingdom and.
authors.forename: Atul
authors.initials: A
authors.lastname: Mehta
authors.affiliation: Department of Internal Medicine I, Division of Cardiology and Nephrology, Comprehensive Heart Failure Center and Fabry Center for Interdisciplinary Therapy, University Hospital Wuerzburg, Wuerzburg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Oder
authors.affiliation: Department of Cardiology, St. Bartholomew's Hospital and University College London, London, United Kingdom.
authors.forename: Oliver T
authors.initials: OT
authors.lastname: Watkinson
authors.affiliation: Department of Cardiology, St. Bartholomew's Hospital and University College London, London, United Kingdom.
authors.forename: Perry M
authors.initials: PM
authors.lastname: Elliott
authors.affiliation: Departments of Endocrinology and Metabolism and.
authors.forename: Gabor E
authors.initials: GE
authors.lastname: Linthorst
authors.affiliation: Pediatrics, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Frits A
authors.initials: FA
authors.lastname: Wijburg
authors.affiliation: Departments of Endocrinology and Metabolism and.
authors.forename: Marieke
authors.initials: M
authors.lastname: Biegstraaten
authors.affiliation: Departments of Endocrinology and Metabolism and.
authors.forename: Carla E
authors.initials: CE
authors.lastname: Hollak
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D000795:Fabry Disease / Q000145:classification* / Q000235:genetics / Q000401:mortality*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012189:Retrospective Studies; D015996:Survival Rate
keywords: Fabry-s disease; alpha galactosidase A; natural disease course; natural history; phenotype