The Kidney in Fabry Disease

Abstract

Fabry disease is a rare cause of end-stage renal disease. Renal pathology is notable for diffuse deposition of glycosphingolipid in the renal glomeruli, tubules, and vasculature. Classical patients with mutations in the a-galactosidase A gene accumulate globotriaosylceramide and become symptomatic in childhood with pain, gastrointestinal disturbances, angiokeratoma, and hypohidrosis. Classical patients experience progressive loss of renal function and hypertrophic cardiomyopathy, with severe clinical events including end-stage renal disease, stroke, arrhythmias, and premature death. The pathophysiological mechanisms by which endothelial cells, podocytes, smooth muscle cells, and tubular dysfunction occur in Fabry disease are poorly characterized and understood. This review evaluates the new evidence in pathophysiology of Fabry nephropathy, highlighting the necessity of early identification of individuals with Fabry disease.

Reduced α-galactosidase A activity in zebrafish (Danio rerio) mirrors distinct features of Fabry nephropathy phenotype

“…4 A). Similar findings have been reported in human Fabry nephropathy [68] , [69] , [70] , [71] but not in other FD model [29] , [72] .…”

Epidemiological and clinical profile of patients with fabry disease

“…This disease is defined as an inborn error of X-linked inheritance pattern and secondary to mutations in the lysosomal αgalactosidase A (α-GAL). [3][4][5] The phenotypic result in the total or partial inability to catabolize lipids with terminal residues of α-galactosyl, mainly globotriaosylceramide (Gb-3), which progressively accumulate in lysosomes in the endothelium, podocytes, tubular epithelial cells, cells myocardial, valvular fibroblasts, dorsal ganglia root neurons and autonomic nervous system, which can lead to renal, cardiac and cerebrovascular complications. [5][6][7] The prevalence of Fabry disease among 1: 17,000 to 1: 117,000 males in Caucasian populations is further estimated.…”