TY  - JOUR
A1  - Weidemann, Frank
A1  - Sanchez-Nino, Maria D.
A1  - Politei, Juan
A1  - Oliveira, João-Paulo
A1  - Wanner, Christoph
A1  - Warnock, David G.
A1  - Oritz, Alberto
T1  - Fibrosis: a key feature of Fabry disease with potential therapeutic implications
JF  - Orphanet Journal of Rare Diseases
N2  - 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.
KW  - Fabry
KW  - fibrosis
KW  - podocyte
KW  - Lyso-Gb3
KW  - kidney
KW  - enzyme replacement therapy
KW  - alpha-galactosidase-A
KW  - focal semental glomerulosclerosis
KW  - cardiovascular magnetic-resonance
KW  - left-ventricular hypertrophy
KW  - biopsy findings
KW  - agalsidase-beta
KW  - natural-history data
KW  - cardiac energy metabolism
KW  - randomized controlled trial
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124773
SN  - 1750-1172
VL  - 8
IS  - 116
ER  -