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J Am Soc Nephrol. 2017 May;28(5):1631-1641. doi: 10.1681/ASN.2016090964. Epub 2016 Dec 15.

Characterization of Classical and Nonclassical Fabry Disease: A Multicenter Study.

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Departments of Endocrinology and Metabolism and
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.
Department of Haematology, Royal Free London National Health Service Foundation Trust and University College London, London, United Kingdom and.
Department of Cardiology, St. Bartholomew's Hospital and University College London, London, United Kingdom.
Departments of Endocrinology and Metabolism and.
Pediatrics, Academic Medical Center, Amsterdam, The Netherlands.


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.


Fabry-s disease; alpha galactosidase A; natural disease course; natural history; phenotype

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