BACKGROUND: Enzyme replacement therapy (ERT) with recombinant human α-galactosidase has been available for the treatment of Fabry disease since 2001 in Europe and 2003 in the USA. Treatment outcomes with ERT are dependent on baseline patient characteristics, and published data are derived from heterogeneous study populations. METHODS: We conducted a comprehensive systematic literature review of all original articles on ERT in the treatment of Fabry disease published up until January 2017. This article presents the findings in adult male patients. RESULTS: Clinical evidence for the efficacy of ERT in adult male patients was available from 166 publications including 36 clinical trial publications. ERT significantly decreases globotriaosylceramide levels in plasma, urine, and in different kidney, heart, and skin cell types, slows the decline in estimated glomerular filtration rate, and reduces/stabilizes left ventricular mass and cardiac wall thickness. ERT also improves nervous system, gastrointestinal, pain, and quality of life outcomes. CONCLUSIONS: ERT is a disease-specific treatment for patients with Fabry disease that may provide clinical benefits on several outcomes and organ systems. Better outcomes may be observed when treatment is started at an early age prior to the development of organ damage such as chronic kidney disease or cardiac fibrosis. Consolidated evidence suggests a dose effect. Data described in male patients, together with female and paediatric data, informs clinical practice and therapeutic goals for individualized treatment.

2nd Department of Medicine Department of Cardiovascular Medicine 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Cardiovascular Department San Donato Hospital Arezzo Italy

Department of Genetics São João Hospital Centre and Faculty of Medicine and Instituto de Investigação e Inovação em Saúde University of Porto Porto Portugal

Department of Internal Diseases No 1 1 M Sechenov 1st Moscow State Medical University Moscow Russian Federation

Department of Internal Medicine University Hospital of Zurich and University of Zurich Zurich Switzerland

Department of Nephrology Infermi Hospital Rimini Italy

Department of Neurology University of Erlangen Nuremberg Erlangen Germany

Department of Paediatrics University of Torino Torino Italy

Division of Medicine Turku University Hospital University of Turku Turku Finland

Division of Nephrology University Clinic University of Würzburg Würzburg Germany

French Referral Center for Fabry disease Division of Medical Genetics and INSERM U1179 University of Versailles Paris Saclay University Montigny France

INSERM U1018 University of Paris Sud University of Paris Descartes Paris France

Mark Holland Metabolic Unit Salford Royal NHS Foundation Trust Salford United Kingdom

Service de Cardiologie Hôpitaux Universitaires de Genève Geneva Switzerland

Serviço de Neurologia Hospital Egas Moniz Centro Hospitalar de Lisboa Ocidental; CEDOC Faculdade de Ciências Médicas Universidade Nova de Lisboa Lisboa Portugal

University College London and Barts Heart Centre London United Kingdom

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