PMC3549770_01
a. Immunofluorescence with IgA positive staining in the mesangium, which is diagnostic for IgAN. b. Advanced lesion with diffuse interstitial fibrosis and sclerotic glomerulus. IgAN was confirmed by immunofluorescence. No swollen podocytes indicative of FD are seen (Jones methenamine silver stain; high power field). c. Electron microscopy from paraffin embedded tissue. Small dense deposits in mesangial area. Simultaneously lamellated lipid inclusions (so-called myeloid bodies) are shown.
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F1
In a renal biopsy sample, immunofluorescence and light microscopy [Figure 1a,1b] showed an advanced form of mesangioproliferative IgAN with marked scarring and epithelial crescents (in two glomeruli of the 12, the remaining 10 glomeruli were completely sclerotic) and vascular changes as a part of hypertension (electron microscopy was not performed because only sclerotic glomerulus was present in the sample). With this knowledge we performed additional electron microscopy from archive paraffin embedded kidney tissue [Figure 1c and additionally showed dense deposits in paramesangial areas as a part of IgAN, and podocytes with inclusions of so-called zebra bodies and myelin figures characteristic of FD.
Pedigree of the family of the first patient.
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F2
Other 8 relatives were newly diagnosed with FD [3 hemizygous and 5 heterozygous, Figure 2].
PMC3549770_02
a. Positive mesangial IgA staining in immunofluorescence (high power field). b. Light microscopy - glomerulus with remarkably enlarged podocytes with many vacuoles in their cytoplasm. Swollen lacy cytoplasm of podocytes is indicative of FD (Jones methenamine silver stain; high power field). Please note, diagnostic IgA deposits in mesangium were shown in immunofluorescence. c. Semithin section stained with toluidin blue showed characteristic "blue inclusions" mainly in podocytes. These features together with large podocytes with vacuolated cytoplasm in light microscopy represent a key to the morphological diagnosis of FD.
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F3
IgAN with remarkably enlarged podocytes. IgAN and a high suspicion of a combination with FD was diagnosed by evaluation using immunofluorescence and light microscopy [Figure 3a, 3b. Electron microscopy [Figure 3c, semithin section] revealed dense deposits in paramesangial areas typical of IgAN and podocytes with inclusive zebra bodies and myelin-like bodies characteristic of FD.
Pedigree of the family of the second patient (the relatives of the proband's mother refused the genetic analysis).
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F4
The mutation analysis also revealed the diagnosis of FD in the patient's mother and sister (both heterozygous) with the same mutation [Figure 4.