Fabry's disease is a rare genetic glycolipid-storage disorder characterized by the deficiency of the lysosomal enzyme a-galactosidase A. This enzyme participates in the catabolism of the glycosphingolipid globotriaosylceramide (Gb3) by specifically cleaving its terminal s-linked galactose residue. Progressive accumulation of Gb3 and related glycosphingolipids in vascular endothelial lysosomes of the kidneys, heart, skin and brain leads to several chronic symptoms such as debilitating neuropathic pain and characteristic cutaneous lesions called angiokeratomas. As vital organs are affected with age, premature death usually occurs in the fourth or fifth decade of life due to renal, cardiac or cerebral complications. Agalsidase alfa is delivered to its lysosomal site of action via the recognition of its mannose-6-phosphate (M6P) residues by specific M6P receptors on the cell surface followed by endocytosis. In clinical trials, twice weekly intravenous infusions of agalsidase alfa over six months to one year have been found to be safe and effective in reversing the accumulation of microvascular endothelial deposits of globotriaosylceramide in the kidneys, heart and skin.
Transkaryotic Therapies (US)
Treatment of Fabry
Disease.
ChEBI: Eliglustat tartrate is a tartrate that is the hemitartrate salt of eliglustat. A ceramide glucosyltransferase inhibitor used (as its tartrate salt) for treatment of Gaucher's disease. It has a role as an EC 2.4.1.80 (ceramide glucosyltransferase) inhibitor. It contains an eliglustat(1+).
Replagal (Transkaryotic Therapies).
Treatment of Fabry disease. Only to be prescribed by
specialist centres.
Potentially hazardous interactions with other drugs
Fabrazyme should not be administered with
chloroquine, amiodarone, benoquin or gentamicin
due to a theoretical risk of inhibition of intra-cellular
α-galactosidase activity.
Metabolic degradation pathway similar to other proteins.
