Bedside stereomicroscopy of renal biopsies may lead to a rapid diagnosis of Fabry's disease

Einar Svarstad1, Bjarne M. Iversen1 and Leif Bostad2

1 Renal Research Group, Institute of Medicine and 2 The Gade Institute, Department of Pathology, University of Bergen, Bergen, Norway

Correspondence and offprint requests to: Einar Svarstad, Renal Research Group, Medical Dept, N-5021 Haukeland University Hospital, Norway. Email: einar.svarstad{at}helse-bergen.no

Keywords: Fabry's disease; renal biopsy; stereomicroscopy

Case

A 43-year-old female Fabry patient presented with asymptomatic slight albuminuria (0.043 g/l), normal glomerular filtration rate (120 ml/min/1.73 m2) and normal echocardiography. In younger age she had complained of typical burning pains in her extremities. A renal biopsy was done in the routine work-up, according to our ‘Fabry protocol’. The biopsy findings (16 G needle) are shown in Figures 1A and 1B. Figure 1A demonstrates the white-coloured superficial glomeruli seen in the stereomicroscope immediately after the biopsy procedure. The biopsy specimen is examined with 10–40x magnification in a drop of formaldehyde and illuminated by sharp, concentrated light from above. Subsequent light microscopy (Figure 1B) showed typical podocyte accumulation of glycosphingolipids in the same patient (McDowell's fixative).



View larger version (58K):
[in this window]
[in a new window]
 
Fig. 1. (A) Multiple superficial white glomeruli (arrows) in the stereomicroscope (magnification: x40) in a heterozygous Fabry patient. The white colour is caused by the lysosomal lipid accumulations in podocytes, shown as numerous dark blue cytoplasmic granules in light microscopy of the biopsy material (magnification: x510; biopsy material fixed in McDowell's fixative, embedded in Epon and stained with toluidine blue) (B). For comparison, the stereomicroscopic (magnification: x40) reddish glomeruli (arrows) from a patient with IgA nephropathy and normal podocytes are shown in (C).

 
Discussion

We have noticed that the visible glomeruli in biopsies from both hemizygous and heterozygous Fabry patients appear with a striking white colour in stereomicroscopy. The white colour is probably caused by the lipid content of the glycosphingolipid deposits in the podocytes. This colour is markedly different from the usual reddish-coloured glomeruli seen in patients with normal kidneys and all other types of renal disease we have seen, as demonstrated by the bedside stereomicroscopic findings in a patient with IgA nephritis, normal podocytes, patchy tubulointerstitial scarring and slightly elevated serum creatinine (Figure 1C).

The clinical diagnosis of Fabry's disease may be difficult in non-classic phenotypes and when a family history is lacking [1–3] and the diagnosis may be missed in inexperienced hands if only routine light microscopy is done. In our department, renal biopsy specimens are subject to routine stereomicroscopy by an experienced clinician. We conclude that an incidental finding of white glomeruli in the bedside stereomicroscopic examination of a renal biopsy should raise the suspicion and present an immediate clue to the Fabry diagnosis. A second biopsy specimen fixed in glutaraldehyde (McDowell's fixative) for light microscopy and electron microscopy will secure the morphological diagnosis of Fabry's disease.

Conflict of interest statement. None declared.

References

  1. Desnick RJ, Ioannou YA, Eng CM. {alpha}-Galactosidase A deficiency: Fabry disease. In: Scriver CR, Beaudet AL, Sly WS et al., eds. The Metabolic and Molecular Bases of Inherited Disease, 8th edn. McGraw-Hill, New York: 2001; 3733–3774
  2. Nakao S, Kodama C, Takenaka T et al. Fabry disease: detection of undiagnosed hemodialysis patients and identification of a ‘renal variant’ phenotype. Kidney Int 2003; 64: 801–807[ISI][Medline]
  3. Grünfeld JP. How to improve the early diagnosis of Fabry's disease? Kidney Int 2003; 64: 1136–1137[ISI][Medline]




This Article
Extract
FREE Full Text (PDF)
Alert me when this article is cited
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in ISI Web of Science
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Disclaimer
Request Permissions
Google Scholar
Articles by Svarstad, E.
Articles by Bostad, L.
PubMed
PubMed Citation
Articles by Svarstad, E.
Articles by Bostad, L.