Fibrosis: a key feature of Fabry disease with potential therapeutic implications

Orphanet Journal of Rare Diseases

Alberto Ortiz¹  David G Warnock³  Christoph Wanner⁶  João-Paulo Oliveira²  Juan Politei⁴  Maria D Sanchez-Niño⁵  Frank Weidemann⁶ 

[1] Unidad de Dialisis, IIS-Fundacion Jimenez Diaz, Av Reyes católicos 2, Madrid, 28040, Spain;Centro Hospitalar de São João, Porto, Portugal;University of Alabama at Birmingham, Birmingham, AL, USA;Trinity Dupuytren Clinic, Neurology department, Buenos Aires, Argentina;IDIPAZ/REDINREN, Madrid, Spain;Department of Medicine, Divisions of Cardiology and Nephrology, The Comprehensive Heart Failure Center at the University of Würzburg, Würzburg, Germany

关键词: Enzyme replacement therapy;    Heart;    Kidney;    Lyso-Gb3;    Podocyte;    Fibrosis;    Fabry;   

Others  :  863626
DOI  :  10.1186/1750-1172-8-116

 received in 2013-04-22, accepted in 2013-08-01,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Weidemann et al.; licensee BioMed Central Ltd.

【 图 表 】

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