Kidney nontumor
Hereditary renal disease
Fabry’s disease

Author: Nikhil Sangle, M.D. (see Authors page)

Revised: 20 November 2017, last major update November 2017

Copyright: (c) 2003-2017, PathologyOutlines.com, Inc.

PubMed Search: Fabry’s disease [title] "loattrfree+full+text"[sb]
Cite this page: Sangle, N. Fabry disease. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/kidneyfabry.html. Accessed November 12th, 2018.
Definition / general
  • Also called alpha-galactosidase A deficiency, angiokeratoma corporis diffusum universale
  • X linked (Xq22.1) recessive lysosomal storage disease which causes deficiency in lysosomal alpha-galactosidase A, which catabolizes neutral glycosphingolipids
  • Deficiency causes intracellular accumulation of galabiosylceramide (ceramide trihexoside) and digalactosyl ceramide within skin, renal glomeruli, renal tubular epithelium, blood vessels, corneal epithelium, myocardium and ganglion cells
Clinical features
  • Affects 1 per 40,000
  • Highly penetrant in hemizygous males with symptoms at infancy or childhood
  • Later presentation in heterozygous females, who have more variable severity due to variable lyonization of X chromosome and may have normal leukocyte alpha-galactosidase A activity
  • Clinical symptoms include angiokeratomas on skin of abdomen, buttocks, lips, genitalia and upper thighs
  • Also hematuria and proteinuria progressing to renal failure, corneal dystrophy and recurrent shooting pains in legs
  • Death due to renal, cardiac or cerebrovascular disease at age 40+ years
Diagnosis
  • Low blood or urine levels of alpha-galactosidase by enzymatic assay (may be normal in female heterozygotes)
  • Elevated ceramide trihexoside in urine by thin layer chromatography
  • Immunostains for ceramide trihexoside
  • In women, must perform DNA mutation analysis of alpha-galactosidase A gene to exclude carrier state
  • Patients may present with advanced disease identifiable only by ultrastructural studies (Ultrastruct Pathol 2010;34:307)
Case reports
Treatment
  • Recombinant human alpha-galactosidase A replacement therapy
Microscopic (histologic) description
    Kidney:
  • Enlarged and bubbly, clear vacuoles in visceral epithelium (demonstrated by trichrome stain), parietal epithelium, mesangial cells, endothelial cells, vascular smooth muscle and distal tubular cells
  • Narrowing and thrombosis of arteries and arterioles
  • Patchy tubular atrophy and interstitial fibrosis
  • Progression to focal segmental and global glomerulosclerosis
Microscopic (histologic) images

Images hosted on other servers:
Missing Image

Various images including EM

Missing Image

Global sclerosis,
segmental sclerosis
with moderate interstitial
fibrosis

Missing Image

Figure 1: vacuolar change in renal tubular cells with large nodular aggregates of foam cells
Figure 2: enlarged glomeruli due to segmental vacuolar changes in visceral epithelial cells
Figure 3: strong oil-red-O staining of vacuolated cells
Figure 4: EM shows abundant whorled lamellated electron dense myelin-like bodies lined by single membranes; various images including EM

Immunofluorescence description
  • Negative
Positive stains
  • PAS, Oil red O, Sudan black and Luxol fast blue (stain glycolipid and phospholipid-like material)
Electron microscopy description
  • Characteristic single membrane bound intracellular inclusions (myelin-like figures, zebra bodies), that are 0.1 to 10 microns in diameter, round and lamellated with concentric electron dense layers, found in endothelial and smooth muscle cells, myocardium, fibroblasts and glomerular epithelium; deposits reduced after enzyme therapy (Clin Nephrol 2009;71:550)
  • Changes also present in urine sediment (Arch Pathol Lab Med 1981;105:361)
Electron microscopy images

Images hosted on other servers:
Missing Image

Electron dense lamellar
inclusion bodies in
cytoplasm of skin
fibroblasts
Molecular / cytogenetics description
Differential diagnosis
  • Foam cell change of Gaucher’s disease, gangliosidoses, fucosidosis, mucopolysaccharidoses (all have different intracellular distribution and ultrastructural features of inclusions, lack electron dense myeloid bodies and can detect by laboratory assays)
  • Treatment with chloroquine, amiodarone or aminoglycosides (have similar myelin-like figures, Hum Pathol 2003;34:285)