title: Curative hepatorenal transplantation in systemic amyloidosis caused by the Glu526Val fibrinogen alpha-chain variant in an English family.
abstract: A 53-year-old English woman who had been thought to have systemic monoclonal immunoglobulin light chain (AL) amyloidosis was investigated further because of her unusually long 17-year history and a suggestion of renal disease in the family. She was found to have the Glu526Val fibrinogen alpha-chain variant that causes autosomal dominant hereditary systemic amyloidosis. This has not previously been described in a British family. The mutant gene was associated with the same haplotype as in all other reported cases, suggesting a common founder. The patient had already received a renal transplant, but the graft failed within 6 years due to amyloid deposition. Progressive hepatic amyloidosis eventually caused liver failure, although the function of other organs was well preserved. She therefore received hepatic and renal transplants to replace the failed organs and the hepatic source of the amyloidogenic variant fibrinogen. Three years later she is completely well and has no amyloid deposits identifiable by serum amyloid P component scintigraphy. This is the first detailed report of hepatic transplantation for liver failure caused by amyloidosis of any type. The substantial follow-up suggests that fibrinogen alpha-chain amyloidosis is one of the inherited metabolic diseases that can be cured by liver transplantation. The mutation underlying Glu526Val fibrinogen alpha-chain amyloidosis is incompletely penetrant and has a variable phenotype that can clinically mimic AL amyloidosis. Hereditary fibrinogen amyloidosis may be more prevalent than previously suspected and, since AL amyloid is sometimes a diagnosis of exclusion, genotyping for other amyloidogenic proteins is mandatory in all cases in which the amyloid fibrils cannot be positively identified as AL.
authors.affiliation: Centre for Amyloidosis & Acute Phase Proteins, Department of Medicine, Royal Free and University College Medical School, Royal Free Campus, London, UK. j.gillmore@rfc.ucl.ac.uk
authors.forename: J D
authors.initials: JD
authors.lastname: Gillmore
authors.forename: D R
authors.initials: DR
authors.lastname: Booth
authors.forename: M
authors.initials: M
authors.lastname: Rela
authors.forename: N D
authors.initials: ND
authors.lastname: Heaton
authors.forename: V
authors.initials: V
authors.lastname: Rahman
authors.forename: A J
authors.initials: AJ
authors.lastname: Stangou
authors.forename: M B
authors.initials: MB
authors.lastname: Pepys
authors.forename: P N
authors.initials: PN
authors.lastname: Hawkins
mesh_terms: D000686:Amyloidosis / Q000235:genetics / Q000601:surgery*; D004739:England; D005260:Female; D005340:Fibrinogen / Q000235:genetics*; D005500:Follow-Up Studies; D006801:Humans; D007674:Kidney Diseases / Q000601:surgery; D016030:Kidney Transplantation; D008099:Liver / Q000000981:diagnostic imaging; D008107:Liver Diseases / Q000601:surgery; D016031:Liver Transplantation; D008875:Middle Aged; D009154:Mutation; D010446:Peptide Fragments / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D011877:Radionuclide Imaging; D013154:Spleen / Q000000981:diagnostic imaging
chemical_list: D010446:Peptide Fragments; D005340:Fibrinogen