Hereditary fibrinogen A alpha-chain amyloidosis: phenotypic characterization of a systemic disease and the role of liver transplantation.
Variants of fibrinogen A alpha-chain (AFib) cause the most common type of hereditary renal amyloidosis in Europe and, possibly, the United States as well. Variant fibrinogen is produced in the liver, and solitary renal allografts fail within 1 to 7 years with recurrent amyloidosis. We assessed 22 AFib patients for combined liver and kidney transplantation (LKT) and report the clinical features and outcome. Twenty-one had E526V and 1, the R554L variant. Coronary atherosclerosis was identified in 68% and systemic atheromatosis in 55%. Vascular atheroma excised at endarterectomy and endomyocardial biopsies contained purely variant fibrinogen amyloid. Half had autonomic neuropathy. Six of 9 patients who underwent LKT are alive (67%), with good allograft function and no amyloidosis at median 67 months (range, 33-155 months) of follow-up. Serial technetium-99m-labeled dimercaptosuccinic acid ((99m)Tc-DMSA) renal scintigraphy in 2 cases of preemptive LKT demonstrated preserved native kidney residual function at 5 years. Four explanted livers were used successfully for domino transplantation. Fibrinogen amyloidosis is a systemic amyloid disease with visceral, vascular, cardiac, and neurologic involvement. LKT is curative; however, cardiovascular amyloidosis may preclude this option. Our data encourage evaluation of preemptive solitary liver transplantation early in the course of amyloid nephropathy to prevent hemodialysis and kidney transplantation.
Stangou
Arie J
AJ
Institute of Liver Studies and Amyloidosis Treatment Centre, King's College Hospital, London SE5 9RS, United Kingdom. arie.stangou@kcl.ac.uk
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Nicholas R
NR
Hendry
Bruce M
BM
Rela
Mohamed
M
Portmann
Bernard
B
Wendon
Julia
J
Monaghan
Mark
M
Maccarthy
Philip
P
Buxton-Thomas
Muriel
M
Mathias
Christopher J
CJ
Liepnieks
Juris J
JJ
O'Grady
John
J
Heaton
Nigel D
ND
Benson
Merrill D
MD
D000328:Adult; D028226:Amyloidosis, Familial / Q000000981:diagnostic imaging / Q000473:pathology*; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology; D002319:Cardiovascular System / Q000473:pathology; D005260:Female; D005340:Fibrinogen / Q000235:genetics*; D006801:Humans; D016030:Kidney Transplantation / Q000000981:diagnostic imaging; D016031:Liver Transplantation / Q000000981:diagnostic imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009422:Nervous System Diseases / Q000150:complications / Q000473:pathology; D018579:Patient Selection; D010641:Phenotype; D011877:Radionuclide Imaging; D019783:Technetium Tc 99m Dimercaptosuccinic Acid; D016896:Treatment Outcome; D014463:Ultrasonography
C464794:fibrinogen Aalpha; D019783:Technetium Tc 99m Dimercaptosuccinic Acid; D005340:Fibrinogen