BACKGROUND: Hereditary amyloidosis with predominant renal disease can be caused 
by mutations in the gene encoding the fibrinogen Aα-chain (AFib). Here, we 
describe the clinical course of AFib amyloidosis associated with the rare R554L 
mutation, and the significance of extrarenal amyloid deposits and their possible 
influence on cardiovascular morbidity.
METHODS: We report on 101 members of a family after having conducted patient 
interviews, chart review, genetic testing, renal biopsies and assessment for 
extrarenal amyloid deposition.
RESULTS: Ten family members had chronic kidney disease with late-onset gross 
proteinuria and a variable course of declining renal function, starting in the 
fourth decade of life. In two affected living members, we identified the AFib 
R554L mutation. Renal biopsies from two affected members revealed almost 
complete obliteration of the mesangial glomerular architecture, although kidney 
function was only moderately impaired. There was neither evidence of extrarenal 
amyloidosis nor accelerated atherosclerosis.
CONCLUSIONS: Renal amyloidosis associated with the R554L AFib variant dominated 
the clinical picture in this family, which was similar to that associated with 
the much more prevalent E526V mutation. Although it has been hypothesized that 
vascular deposits of fibrinogen amyloid may be associated with accelerated 
atherosclerosis, there was no suggestion of this in this particular kindred.