Renal pathological changes in Fabry disease

Abstract

Fabry disease is a rare X-linked disorder, characterized by deficient activity of the lysosomal enzyme alpha-galactosidase A. This leads to systemic accumulation of the glycosphingolipid globotriaosylceramide (Gb3) in all body tissues and organs, including the kidney. Renal manifestations are less evident in female heterozygotes than in male hemizygotes, according to the Lyon hypothesis. Accumulation of Gb3 occurs mainly in the epithelial cells of Henle's loop and distal tubule, inducing early impairment in renal concentrating ability; involvement of the proximal tubule induces Fanconi syndrome. All types of glomerular cells are involved, especially podocytes, and glomerular proteinuria may occur at a young age. The evolution of renal Fabry disease is characterized by progressive deterioration of renal function to end-stage renal failure (ESRF). Ultrastructural study of kidney biopsies reveals typical bodies in the cytoplasm of all types of renal cells, characterized by concentric lamellation of clear and dark layers with a periodicity of 35-50 A. Management of progressive renal disease requires dietetic and therapeutic strategies, usually indicated in developing chronic renal failure, with dialysis and renal transplantation required for patients with ESRF. The recent development of enzyme replacement therapy, however, should make it possible to prevent or reverse the progressive renal dysfunction associated with Fabry disease.

Targeted Screening of Fabry Disease in Male Hemodialysis Patients in Brazil Highlights Importance of Family Screening

“…FD has been described in several ethnic groups with an estimated prevalence of 1:40,000 male subjects [1]. Presenting with an X-linked inheritance pattern, there is a complete or partial inability to catabolize lipids with terminal alpha-galactosyl residues, mainly globotriaosylceramide (GL-3), believed to trigger a cascade of cellular events [1,2,3,4]. In the ‘classic' presentation of the disease, symptoms often manifest in childhood with acroparesthesia, Fabry ‘pain crises', angiokeratoma, hypohidrosis or anhidrosis and gastrointestinal symptoms with renal, cardiac and cerebrovascular complications occurring by the 3rd or 4th decade of life.…”

The Liquid Crystalline in Normal Renal Development Amplifies the Comprehension for Anderson-Fabry Disease

“…Within the concentric lamellation-structure, myelin bodies exhibit liquid crystal characteristics and can be identified by a Maltese cross when observed between the polarizer and analyzer of polarizing microscopes. At the present time Maltese-cross lipid bodies detected with osmiophilic lamellation at the ultrastructure level and Maltese cross birefringence at the microstructure level has become one of the typical diagnostic characteristics for evaluating Anderson-Fabry disease [6,[8][9][10][11]. In this paper, our recent data reveals that Maltese cross birefringence is also present in normal biological processes during the development of mesonephros and metanephros.…”

“…From renal insufficiency to end-stage renal failure, patients can suffer throughout life. The intracellular and extracellular accumulation of glycosphingolipids in the renal epithelium, endothelium and other different cells is the direct cuase of these complications [6,[8][9][10][11]. Enzyme replacement and enzyme enhancement therapy have proved effective for the improvement of renal and cardiac function for patients suffering from the disease.…”

“…Ultrastructural studies reveal that the cytoplasmic lysosomes exhibit concentric lamellation-osmiophilic myelin bodies in all types of renal cells. These myelin bodies critically damage the glomerular filtration barrier and take responsibility for disrupting the proteinuric mechanisms [6]. Furthermore, the involvement of myelin bodies with the Bowman's Capsule epithelial cells, the glomerular capillary, and the glomerular afferent arterioles contributes to the progressive loss of renal function [6].…”

“…These myelin bodies critically damage the glomerular filtration barrier and take responsibility for disrupting the proteinuric mechanisms [6]. Furthermore, the involvement of myelin bodies with the Bowman's Capsule epithelial cells, the glomerular capillary, and the glomerular afferent arterioles contributes to the progressive loss of renal function [6]. In the urine of Anderson-Fabry patients, these myelin bodies from pathological lesions are excreted in large amounts [7].…”