Plasma protein fibrinogen variants cause fibrinogen Aα-chain (AFib) amyloidosis, which presents with hypertension, proteinuria, and azotemia. Six AFib mutations have been reported thus far. We identified three patients who presented with marked proteinuria and serum creatinine elevations. Their kidney biopsies revealed destruction of the glomerular architecture by amyloid deposits with typical, apple-green birefringence in polarized light after Congo red staining. We found immunoreactivity against fibrinogen, which is typical for this type of amyloidosis. We sequenced the FGA exon 5 and demonstrated heterozygosity for the p.Glu526Val mutation in all three cases. This amino acid substitution is the most common fibrinogen Aα-chain variant causing AFib amyloidosis. The mutation has been reported in individuals of European and American descent but not yet in German patients. AFib amyloidosis should therefore be considered an important differential diagnosis in German patients with renal amyloidosis. In the cases described here, the use of antibodies directed against fibrinogen, followed by direct gene sequencing, revealed the underlying cause.
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fibrinogen Aα-chain gene
hereditary renal amyloidosis
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This project was supported by grants of the European Union (EU FP6 EURAMY). We wish to thank Dr. August (Münster), Prof. Krenn (Trier) and Prof. Waldherr (Heidelberg) for kindly providing the kidney biopsies for immunohistochemical analyses, Dr. Thomas Ackermann (Mechernich) and Dr. Kerstin Traser (Halle/Saale) for admission of the patients and Prof. Luft (Berlin) for his critical revision of the manuscript.
Conflict of interest statement
We declare that we have no conflict of interest.
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Eriksson, M., Schönland, S., Bergner, R. et al. Three German fibrinogen Aα-chain amyloidosis patients with the p.Glu526Val mutation. Virchows Arch 453, 25–31 (2008). https://doi.org/10.1007/s00428-008-0619-4