Fabry Nephropathy

Abstract

Fabry disease is a rare X-linked recessive lysosomal storage disease. Multiple mutations of the GLA gene lead to a deficient or absent activity of the lysosomal enzyme α-galactosidase A, resulting in progressive glycotriaosylceramide accumulation in many organs. Low α-galactosidase A activity and mutations in the GLA gene confirm the diagnosis. Clinical signs are multisystemic, heterogeneous, and progressive. Renal, cardiac, and neurovascular involvements are the main life-threatening complications, highlighting the importance of an early initiation of enzyme replacement therapy improving long-term outcome. Fabry nephropathy lesions are characterized by a cell vacuolization of glomeruli, tubules, interstitium, and arteries and by ultrastructural myelin bodies. The main histologic differential diagnoses are toxicity of lysosomal inhibitors and other renal lipidoses. Renal biopsies are not necessary for diagnosis but have an important role in the evaluation of disease evolution and treatment efficiency, which is a major challenge for improving outcome and quality of life.

α-d-Gal-cyclophellitol cyclosulfamidate is a Michaelis complex analog that stabilizes therapeutic lysosomal α-galactosidase A in Fabry disease

“…35 LysoGb3 constitutes a signature of Fabry disease and allows diagnostic monitoring of disease progression, 2,3,[36][37][38] and has been linked to neuronopathic pain and renal failure through its effect on nociceptive neurons and podocytes. [39][40][41][42] We investigated whether co-administration of a-cyclosulfamidate 4 and Fig. 4 Competitive ABPP in a-galactosidases.…”

Nail-patella-like renal disease masquerading as Fabry disease on kidney biopsy: a case report

“…However, it is still not clear if individuals with other causes for renal phospholipidosis could also excrete lyso-Gb3. It is important to point out that in FD, myeloid bodies are usually present not only in the podocytes, but also in mesangial cells, endothelial cells, distal tubule, and interstitium whereas in our patient there were inclusions only in the podocytes similar to non-FD causes, and provides a clue that we were dialing with a disease other than FD [23]. The FSGS lesion in our patient is consistent with what has been reported in association with the identified LMX1B variant.…”

Fabry disease—what cardiologists can learn from the nephrologist: a narrative review

“…In advanced Fabry nephropathy histological alterations are already detectable on light microscopy (Figure 3D,E) (31,32). Glomeruli show prominent vacuolization of podocytes, mesangial cells and endothelial cells, reflecting inclusion of storage material, mainly Gb3.…”

“…An adequate method to demonstrate Fabry-specific deposits on light microscopy is toluidine blue staining (Figure 3F,G) (31,32). This method is not part of routine pathological workup and has to be requested if Fabry nephropathy is a differential diagnosis.…”