BACKGROUND: Fabry disease, an inherited lysosomal storage disorder, causes multi-organ pathology resulting in substantial morbidity and a reduced life expectancy. Although Fabry disease is an X-linked disorder, both genders may be affected, but generally to a lesser extent in females. The disease spectrum ranges from classic early-onset disease to non-classic later-onset phenotypes, with complications occurring in multiple organs or being confined to a single organ system depending on the stage of the disease. The impact of therapy depends upon patient- and disease-specific factors and timing of initiation. METHODS: A European panel of experts collaborated to develop a set of organ-specific therapeutic goals for Fabry disease, based on evidence identified in a recent systematic literature review and consensus opinion. RESULTS: A series of organ-specific treatment goals were developed. For each organ system, optimal treatment strategies accounted for inter-patient differences in disease severity, natural history, and treatment responses as well as the negative burden of therapy and the importance of multidisciplinary care. The consensus therapeutic goals and proposed patient management algorithm take into account the need for early disease-specific therapy to delay or slow the progression of disease as well as non-specific adjunctive therapies that prevent or treat the effects of organ damage on quality of life and long-term prognosis. CONCLUSIONS: These consensus recommendations help advance Fabry disease management by considering the balance between anticipated clinical benefits and potential therapy-related challenges in order to facilitate individualized treatment, optimize patient care and improve quality of life.

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

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

Barts Heart Centre University College London London United Kingdom

Cardiovascular Department San Donato Hospital Arezzo Italy

Department of Cardiology Innere Klinik 2 Katharinen Hospital Unna Germany

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 Medical Endocrinology Section 2132 Rigshospitalet Copenhagen University Hospital Copenhagen Denmark

Department of Nephrology Infermi Hospital Rimini Italy

Department of Neurology University of Erlangen Nuremberg Erlangen Germany

Department of Paediatrics Haukeland University Hospital and Department of Clinical Medicine University of Bergen Bergen Norway

Department of Paediatrics Nutrition and Metabolic Diseases Children's Memorial Health Institute Warsaw Poland

Department of Paediatrics University of Torino Torino Italy

Division of Medicine Turku University Hospital Turku Finland

Division of Nephrology University Clinic University of Würzburg Würzburg Germany

Division of Neurological Pain Research and Therapy Department of Neurology Universitätsklinikum Schleswig Holstein Kiel Germany

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

Health in Code A Coruña Spain

Leviev Heart Center Sheba Medical Center Tel Hashomer Tel Aviv University Israel

Lysosomal Storage Disorders Unit Department of Haematology Royal Free London NHS Foundation Trust University College London United Kingdom

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

Neurological Unit St Bassiano Hospital Bassano del Grappa Italy

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

Unidad de Diálisis IIS Fundación Jiménez Díaz UAM IRSIN and REDINREN Madrid Spain

University Heart Center University Hospital of Zurich and University of Zurich Zurich Switzerland

References provided by Crossref.org

Renal and multisystem effectiveness of 3.9 years of migalastat in a global real-world cohort: Results from the followME Fabry Pathfinders registry

A phase III, open-label clinical trial evaluating pegunigalsidase alfa administered every 4 weeks in adults with Fabry disease previously treated with other enzyme replacement therapies

Head-to-head trial of pegunigalsidase alfa versus agalsidase beta in patients with Fabry disease and deteriorating renal function: results from the 2-year randomised phase III BALANCE study

Pegunigalsidase alfa: a novel, pegylated recombinant alpha-galactosidase enzyme for the treatment of Fabry disease

Safety and efficacy of pegunigalsidase alfa in patients with Fabry disease who were previously treated with agalsidase alfa: results from BRIDGE, a phase 3 open-label study

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

The benefits and challenges of family genetic testing in rare genetic diseases-lessons from Fabry disease

U-IMD: the first Unified European registry for inherited metabolic diseases

Cardiomyopathy and kidney function in agalsidase beta-treated female Fabry patients: a pre-treatment vs. post-treatment analysis

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