Vascular complications of Fabry disease: enzyme replacement and other therapies.
Fabry disease is an X-linked glycosphingolipid storage disorder resulting from deficiency of alpha-galactosidase A. Storage of globotriaosylceramide ultimately results in multiorgan pathology, including cerebrovascular, cardiovascular and renal disease. Vascular involvement is evident throughout the body but the mechanisms by which storage on a cellular level leads to end-organ pathology are unknown. Here the evidence for abnormal blood flow, vessel architecture and endothelial function will be reviewed and possible models of vascular pathology discussed. The effects of reversal of storage within vessels by enzyme replacement therapy (ERT) and the possibilities for intervention with additional agents will be considered.


CONCLUSIONS
The pathology of Fabry disease has an important vascular component, although the underlying pathophysiology is unclear. Preliminary evidence suggests that ERT may have beneficial effects on the vascular component of this multisystem disease.
Hughes
D A
DA
Department of Academic Haematology, Royal Free and University College Medical School, London, UK. da.hughes@rfc.ucl.ac.uk
Mehta
A B
AB
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use; D001778:Blood Coagulation Disorders / Q000209:etiology; D001783:Blood Flow Velocity / Q000502:physiology; D004176:Dipyridamole / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000503:physiopathology; D000795:Fabry Disease / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D008657:Metabolic Clearance Rate / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D014281:Trihexosylceramides / Q000097:blood; D014652:Vascular Diseases / Q000209:etiology* / Q000503:physiopathology; D014665:Vasodilator Agents / Q000627:therapeutic use; D000519:alpha-Galactosidase / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D010975:Platelet Aggregation Inhibitors; D014281:Trihexosylceramides; D014665:Vasodilator Agents; D004176:Dipyridamole; C018549:globotriaosylceramide; D000519:alpha-Galactosidase; D001241:Aspirin