Fabry disease is a rare genetic disease and potentially life-threatening condition caused by the accumulation of disease substrate (globotriaosylceramide
, GL-3) in the lysosome due to a dysfunctional or deficient enzyme.
Gb3, or globotriaosylceramide
, is a substrate that accumulates in the cells of Fabry patients and can result in damage to multiple organs including the kidneys and heart.
Novel quantitative method to evaluate globotriaosylceramide
inclusions in renal peritubular capillaries by virtual microscopy in patients with Fabry disease.
Shiga toxin binds to the host cell receptor Gb3 (globotriaosylceramide
, [P.sup.k] blood group antigen).
Although the main cause of anemia in Fabry disease patients is not clearly understood, it is speculated that the reasons were bone marrow accumulation of globotriaosylceramide
or renal insufficiency.
In Fabry disease, there is a progressive increase in the deposition of globotriaosylceramide
(Gb3), a sphingolipid degradation product, within the lysosomes of the epithelial cells of various organs.
Fabry disease (FD, OMIM #301500) is caused by the lysosomal accumulation of complex glycosphingolipids, mainly globotriaosylceramide
(Gb3) and its metabolites .
Impaired glycosphingolipid metabolism leads to systemic lysosomal globotriaosylceramide
accumulation with multiorgan systemic involvement and complex clinical presentation: acroparesthesias, angiokeratoma, hypohidrosis, corneal and lenticular opacities, gastrointestinal and endocrine abnormalities, renal impairment, and neural and cardiovascular disease [1, 2].
Cattle do not contain the Shiga toxin receptor, globotriaosylceramide
, and therefore are asymptomatic in the presence of E.
Fabry disease is an X-linked storage disease due to mutations in the GLA gene encoding the lysosomal enzyme [alpha]-galactosidase A, leading to the accumulation of enzyme substrates, namely, globotriaosylceramide
(Gb3), lyso-globotriaosylceramide (lyso-Gb3), and galabiosylceramide .
Cardiac disease is caused by accumulation of globotriaosylceramide
in all cellular components of the heart.