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Vasculopathy of Fabry Disease: From Fetal Life to Adulthood

Olivier Dormond1, Samuel Rotman2, and Frédéric Barbey3

Fabry disease (FD) is a rare, X-linked, recessive disorder that is caused by deficiency of the enzyme α-galactosidase A [1]. As a result of this enzyme deficiency, neutral glycosphingolipids, predominantly globotriaosylceramide (Gb3), accumulate in almost all tissues, but with a predilection for endothelial cells (EC) and vascular smooth muscle cells (VSMC) of the vascular network, and in extracellular compartments and fluids. This results in renal, cardiovascular, and cerebrovascular ischemic complications leading to premature death in both hemizygous males and severely affected heterozygous females [2]. Therefore, unlike most other sphingolipidoses, the clinical symptoms in FD mostly result from ischemic dysfunction and lesions; these underline the presence of a global vasculopathy, which results from microvascular endothelial disease and/or necrosis and proliferation of VSMC extending from the aorta to the capillaries. To date, it is not clear to what extent the accumulated Gb3 contributes directly to tissue injury manifestations of FD.

The vascular symptoms in FD were extensively described as early as 1947 [3]. Post mortem examinations of male patients revealed an abnormal thickening of the aortic wall caused by swelling of the VSMC. The arterial walls were also thickened in the kidney owing to swelling of EC and VSMC, leading to a considerable reduction in the diameter of the lumens of small arteries in the kidney. Notably, the investigators concluded that this vascular process could not be regarded as simple arteriosclerosis [3].

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