Fabry disease: a morphologic study of 11 cases

Mod Pathol. 2006 Oct;19(10):1295-301. doi: 10.1038/modpathol.3800634. Epub 2006 Jun 23.

Abstract

Fabry disease is a metabolic disorder caused by the genetic deficiency of alpha-galactosidase A. Deposition of glycosphingolipids in podocytes, endothelial cells, and other cell types leads to formation of myelin-like inclusions, which are the hallmark of the disease. In most untreated males, the disorder progresses to end-stage kidney disease. Fabry disease is rare, and no renal biopsy series focusing on pathologic findings has been published in the past 25 years. We retrieved kidney biopsies diagnosed with Fabry disease from our files, and reviewed clinical data as well as the light and electron microscopy. In total, 11 patients were identified: six male subjects aged 17-43 years and five female subjects aged 30-73 years. On average, male patients presented more than 10 years earlier then female patients. A total of 10 patients had proteinuria, two with the nephrotic syndrome. Four male and three female patients had decreased renal function. Light microscopy showed vacuolization of the podocyte cytoplasm and variable glomerular sclerosis. Older patients and males had more advanced glomerular and interstitial sclerosis, but three of the five female patients also had advanced renal disease. Electron microscopy showed the characteristic myelin-like inclusions most prominently in the podocyte cytoplasm. Seven patients also had podocyte foot process effacement. A second type of deposit, unexpected and conspicuous, was identified in three males, and found to be associated with glomerular basement membrane duplications. These deposits were composed of layered membrane-like material, and therefore morphologically distinct from myelin-like inclusions. They probably represent remnants of damaged endothelial cells.

MeSH terms

  • Adolescent
  • Adult
  • Biopsy
  • Fabry Disease / pathology*
  • Female
  • Glomerular Basement Membrane / ultrastructure
  • Humans
  • Inclusion Bodies / ultrastructure
  • Kidney / pathology*
  • Male
  • Podocytes / ultrastructure*
  • Retrospective Studies
  • Severity of Illness Index
  • Sex Factors