INTRODUCTION: Fibrinogen A alpha chain amyloidosis is an autosomal dominant 
disease associated with mutations in the fibrinogen A alpha chain (FGA) gene, 
and it is the most common cause of hereditary renal amyloidosis in the UK. 
Patients typically present with kidney impairment and progress to end-stage 
renal disease over a median time of 4.6 years.
METHODS: Six patients presented with proteinuria, hypertension, and/or lower 
limb edema and underwent detailed clinical and laboratory investigations.
RESULTS: A novel FGA gene mutation was identified in each case: 2 frameshift 
mutations F521Sfs*27 and G519Efs*30 and 4 single base substitutions G555F, 
E526K, E524K, R554H. In 5 subjects, extensive amyloid deposits were found solely 
within the glomeruli, which stained specifically with antibodies to fibrinogen A 
alpha chain, and in one of these cases, we found coexistent fibrinogen A alpha 
chain amyloidosis and anti-glomerular basement membrane antibody disease. One 
patient was diagnosed with light-chain amyloidosis after a bone marrow 
examination revealed a small clonal plasma cell population, and laser 
microdissection of the amyloid deposits followed by liquid chromatography and 
tandem mass spectrometry identified kappa light chain as the fibril protein.
DISCUSSION: We report 6 novel mutations in the FGA gene: 5 were associated with 
renal fibrinogen A alpha chain amyloidosis and 1 was found to be incidental to 
light-chain amyloid deposits discovered in a patient with a plasma cell 
dyscrasia. Clinical awareness and suspicion of hereditary amyloidosis 
corroborated by genetic analysis and adequate typing using combined 
immunohistochemistry and laser microdissection and mass spectrometry is valuable 
to avoid misdiagnosis, especially when a family history of amyloidosis is 
absent.