Curative hepatorenal transplantation in systemic amyloidosis caused by theGlu526Val fibrinogen alpha-chain variant in an English family

A 53-year-old English woman who had been thought to have systemic monoclona l immunoglobulin light chain (AL) amyloidosis was investigated further beca use 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. Thi s has not previously been described in a British family, The mutant gene wa s associated with the same haplotype as in all of her reported cases, sugge sting a common founder. The patient had already received a renal transplant , but the graft failed within 6 years due to amyloid deposition. Progressiv e hepatic amyloidosis eventually caused liver failure, although the functio n of other organs was well preserved. She therefore received hepatic and re nal 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 scint igraphy. This is the first detailed report of hepatic transplantation for l iver failure caused by amyloidosis of any type. The substantial follow-up s uggests that fibrinogen alpha-chain amyloidosis is one of the inherited met abolic diseases that can be cured by liver transplantation. The mutation un derlying Glu526Val fibrinogen alpha-chain amyloidosis is incompletely penet rant and has a variable phenotype that can clinically mimic AL amyloidosis. Hereditary fibrinogen amyloidosis may be more prevalent than previously su spected and, since AL amyloid is sometimes a diagnosis of exclusion, genoty ping for other amyloidogenic proteins is mandatory in all cases in which th e amyloid fibrils cannot be positively identified as AL.