title: Cardiac phenotype and clinical outcome of familial amyloid polyneuropathy associated with transthyretin alanine 60 variant.
abstract: OBJECTIVE
  Familial amyloid polyneuropathy (FAP) is a dominantly inherited multi-system disease associated with transthyretin (TTR) mutations. Previous series have predominantly described patients with the TTR variant Val30Met (V30M), which is the most prevalent cause of FAP worldwide. Here, we report the dominant cardiac phenotype and outcome of FAP associated with TTR Thr60Ala (T60A), the most common UK variant.
  
  
  RESULTS
  Sixty consecutive patients with FAP associated with TTR T60A (FAP T60A) were prospectively evaluated in two centres between 1992 and 2009. Median (range) age of symptom development was 63 (45-78) years. A family history of amyloidosis was present in only 37%. Autonomic and peripheral neuropathy were present in 44 and 32 patients, respectively, at diagnosis. Cardiac involvement was evident on echocardiography at diagnosis in 56 patients, but was associated with reduced QRS voltages on electrocardiography in only 16% evaluable cases. Seventeen patients received implantable anti-arrhythmic devices. Median survival was 6.6 years following onset of symptoms and 3.4 years from diagnosis, and correlated with serum N-terminal prohormone brain natriuretic peptide (NT-proBNP) concentration and certain echocardiographic parameters at the latter. Orthotopic liver transplantation (OLT), performed to eliminate the predominant hepatic source of variant TTR T60A protein, was performed in eight patients including one who received a concomitant cardiac transplant. Cardiac amyloidosis progressed in all lone OLT recipients, of whom four died within 5 years.
  
  
  CONCLUSIONS
  Cardiac amyloidosis is almost always present at diagnosis in FAP T60A, and is a major determinant of its poor prognosis. Outcome of liver transplantation in FAP T60A has been discouraging.
authors: National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Royal Free Hospital, Rowland Hill Street, London NW3 2PF,  UK.
authors: Prayman T
authors: PT
authors: Sattianayagam
authors: Angelika F
authors: AF
authors: Hahn
authors: Carol J
authors: CJ
authors: Whelan
authors: Simon D J
authors: SD
authors: Gibbs
authors: Jennifer H
authors: JH
authors: Pinney
authors: Arie J
authors: AJ
authors: Stangou
authors: Dorota
authors: D
authors: Rowczenio
authors: Peter W
authors: PW
authors: Pflugfelder
authors: Zoe
authors: Z
authors: Fox
authors: Helen J
authors: HJ
authors: Lachmann
authors: Ashutosh D
authors: AD
authors: Wechalekar
authors: Philip N
authors: PN
authors: Hawkins
authors: Julian D
authors: JD
authors: Gillmore
mesh_terms: D000368:Aged; D028227:Amyloid Neuropathies, Familial / Q000097:blood / Q000235:genetics* / Q000401:mortality; D001145:Arrhythmias, Cardiac / Q000235:genetics / Q000401:mortality; D009202:Cardiomyopathies / Q000097:blood / Q000235:genetics* / Q000401:mortality; D004562:Electrocardiography; D006801:Humans; D053208:Kaplan-Meier Estimate; D016031:Liver Transplantation / Q000379:methods / Q000401:mortality; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D010641:Phenotype; D011228:Prealbumin / Q000235:genetics*; D011446:Prospective Studies
chemical_list: D010446:Peptide Fragments; D011228:Prealbumin; C109794:pro-brain natriuretic peptide (1-76); C072919:transthyretin, Ala(60)-; D020097:Natriuretic Peptide, Brain