OBJECTIVES: The PRoposing Early Disease Indicators for Clinical Tracking in Fabry Disease (PREDICT-FD) initiative aimed to reach consensus among a panel of global experts on early indicators of disease progression that may justify FD-specific treatment initiation. DESIGN AND SETTING: Anonymous feedback from panellists via online questionnaires was analysed using a modified Delphi consensus technique. Questionnaires and data were managed by an independent administrator directed by two non-voting cochairs. First, possible early indicators of renal, cardiac and central/peripheral nervous system (CNS/PNS) damage, and other disease and patient-reported indicators assessable in routine clinical practice were compiled by the cochairs and administrator from panellists' free-text responses. Second, the panel scored indicators for importance (5-point scale: 1=not important; 5=extremely important); indicators scoring ≥3 among >75% of panellists were then rated for agreement (5-point scale: 1=strongly disagree; 5=strongly agree). Indicators awarded an agreement score ≥4 by >67% of panellists achieved consensus. Finally, any panel-proposed refinements to consensus indicator definitions were adopted if >75% of panellists agreed. RESULTS: A panel of 21 expert clinicians from 15 countries provided information from which 83 possible current indicators of damage (kidney, 15; cardiac, 15; CNS/PNS, 13; other, 16; patient reported, 24) were compiled. Of 45 indicators meeting the importance criteria, consensus was reached for 29 and consolidated as 27 indicators (kidney, 6; cardiac, 10; CNS/PNS, 2; other, 6; patient reported, 3) including: (kidney) elevated albumin:creatinine ratio, histological damage, microalbuminuria; (cardiac) markers of early systolic/diastolic dysfunction, elevated serum cardiac troponin; (CNS/PNS) neuropathic pain, gastrointestinal symptoms suggestive of gastrointestinal neuropathy; (other) pain in extremities/neuropathy, angiokeratoma; (patient-reported) febrile crises, progression of symptoms/signs. Panellists revised and approved proposed chronologies of when the consensus indicators manifest. The panel response rate was >95% at all stages. CONCLUSIONS: PREDICT-FD captured global opinion regarding current clinical indicators that could prompt FD-specific treatment initiation earlier than is currently practised.

Cardiac Imaging Department Barts Heart Centre London UK

Department and Laboratory of Paediatric Metabolic Disorders Gazi University Ankara Turkey

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

Department of Cardiovascular Respiratory Nephrologic Geriatric and Anesthesiologic Sciences University of Rome La Sapienza Rome Italy

Department of Clinical Medicine University of Bergen Bergen Norway

Department of Endocrinology and Clinical Nutrition University Hospital Zurich and University of Zurich Zurich Switzerland

Department of Haematology University College London London UK

Department of Internal Medicine General Hospital Slovenj Gradec Slovenj Gradec Slovenia

Department of Internal Medicine Psychiatry University Hospital Zurich Zurich Switzerland

Department of Internal Medicine Rheumatology Croix Saint Simon Hospital Paris France

Department of Medicine Haukeland University Hospital Bergen Norway

Department of Medicine The University of Melbourne Parkville Campus Melbourne Victoria Australia

Department of Medicine University of Cambridge Cambridge UK

Department of Nephrology Royal Melbourne Hospital Parkville Victoria Australia

Department of Nephrology Royal Perth Hospital Perth Western Australia Australia

Department of Neurology British Hospital of Buenos Aires Buenos Aires Argentina

Department of Pediatrics Taipei Veterans General Hospital Taipei Taiwan

Division of Nephrology Belcolle Hospital Viterbo Italy

Division of Nephrology University of Alabama at Birmingham Birmingham Alabama USA

Fabry International Network Beveren Belgium

Fabry Support and Information Group Concordia Missouri USA

Inborn Errors of Metabolism Reference Center North Lisbon Hospital Center Lisbon Portugal

Inherited Renal Diseases Unit Autonomous University of Barcelona Barcelona Spain

Institute of Clinical Medicine National Yang Ming University Taipei Taiwan

Institute of Metabolic Disease Baylor Research Institute Dallas Texas USA

Instituto de Estudios Inmunológicos y Fisiopatológicos UNLP CONICET La Plata Argentina

Lysosomal Disorders Unit Addenbrooke's Hospital Cambridge UK

Lysosomal Storage Disorders Unit Royal Free Hospital London UK

Medicine Dalhousie University Halifax Nova Scotia Canada

Medicine Department University of Lisbon Lisbon Portugal

Oxford PharmaGenesis Oxford UK

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