title: Fibrosis: a key feature of Fabry disease with potential therapeutic implications.
abstract: Fabry disease is a rare X-linked hereditary disease caused by mutations in the AGAL gene encoding the lysosomal enzyme alpha-galactosidase A. Enzyme replacement therapy (ERT) is the current cornerstone of Fabry disease management. Involvement of kidney, heart and the central nervous system shortens life span, and fibrosis of these organs is a hallmark of the disease. Fibrosis was initially thought to result from tissue ischemia secondary to endothelial accumulation of glycosphingolipids in the microvasculature. However, despite ready clearance of endothelial deposits, ERT is less effective in patients who have already developed fibrosis. Several potential explanations of this clinical observation may impact on the future management of Fabry disease. Alternative molecular pathways linking glycosphingolipids and fibrosis may be operative; tissue injury may recruit secondary molecular mediators of fibrosis that are unresponsive to ERT, or fibrosis may represent irreversible tissue injury that limits the therapeutic response to ERT. We provide an overview of Fabry disease, with a focus on the assessment of fibrosis, the clinical consequences of fibrosis, and recent advances in understanding the cellular and molecular mechanisms of fibrosis that may suggest novel therapeutic approaches to Fabry disease.
authors.affiliation: Department of Medicine, Divisions of Cardiology and Nephrology, The Comprehensive Heart Failure Center at the University of Würzburg.
authors.forename: Frank
authors.initials: F
authors.lastname: Weidemann
authors.forename: Maria D
authors.initials: MD
authors.lastname: Sanchez-Niño
authors.forename: Juan
authors.initials: J
authors.lastname: Politei
authors.forename: João-Paulo
authors.initials: JP
authors.lastname: Oliveira
authors.forename: Christoph
authors.initials: C
authors.lastname: Wanner
authors.forename: David G
authors.initials: DG
authors.lastname: Warnock
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
mesh_terms: D056947:Enzyme Replacement Therapy / Q000379:methods*; D000795:Fabry Disease / Q000188:drug therapy / Q000473:pathology*; D005355:Fibrosis / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D007668:Kidney / Q000473:pathology
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