Mutant fibrinogen A-alpha-chain associated with hereditary renal amyloidosis and peripheral neuropathy.
A middle age Portuguese woman was investigated for renal amyloidosis. She presented with progressive renal failure, proteinuria, hypertension, and sensory symptoms in the feet. Clinical and neurophysiological evaluation disclosed sensory-autonomic neuropathy. Cardiovascular tests and 123-MIBG investigation showed parasympathetic dysfunction and decrease of myocardial innervation, in accordance with small fiber neuropathy, as usually observed in amyloidosis. Immunohistochemical studies revealed AFib amyloidosis and genetic studies the amino acid exchange Glu526Val of the fibrinogen Aalpha-chain mutation, which was also present in one of her sons. The mutant gene in this patient was associated with the same haplotype as all other reported cases of Glu526Val mutations. This is the first reported AFibamyloidosis in Portugal, and the first case of AFib in which sensory and autonomic nerve fiber dysfunction is described, indicating that small nerve fiber lesion can occur in the fibrinogen Aalpha chain mutation. This can be important for prognosis, in particular when liver transplantation is considered for treatment.
de Carvalho
Mamede
M
Department of Neurology, Hospital de Santa Maria, Lisbon, Portugal. mamedemg@mail.telepac.pt
Linke
Reinhold P
RP
Domingos
Fernando
F
Evangelista
Teresinha
T
Ducla-Soares
José Luís
JL
Nathrath
Walter B J
WB
Azevedo-Coutinho
Conceição
C
Lima
Raquel
R
Saraiva
Maria João
MJ
D019943:Amino Acid Substitution / Q000235:genetics*; D028226:Amyloidosis, Familial / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015241:Fibrinogens, Abnormal / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007674:Kidney Diseases / Q000150:complications / Q000151:congenital / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D017354:Point Mutation / Q000235:genetics*
D015241:Fibrinogens, Abnormal