title: Hereditary lysozyme amyloidosis -- phenotypic heterogeneity and the role of solid organ transplantation.
abstract: OBJECTIVE
  Lysozyme amyloidosis (ALys) is a form of hereditary systemic non-neuropathic amyloidosis, which is inherited in an autosomal dominant fashion. Lysozyme, which is the amyloidogenic precursor protein in ALys, is a ubiquitous bacteriolytic enzyme synthesized by hepatocytes, polymorphs and macrophages. The aim of this study is to describe the phenotype and outcome of patients with ALys including the role of solid organ transplantation.
  
  
  METHODS
  Retrospective evaluation of patients with ALys.
  
  
  METHODS
  UK National Amyloidosis Centre.
  
  
  METHODS
  All 16 patients with ALys followed at the centre.
  
  
  RESULTS
  A family history of amyloidosis was present in every affected individual. Although the phenotype was broadly similar amongst those from the same kindred, there were marked phenotypic differences between kindreds who possessed the same amyloidogenic mutation. Symptomatic gastrointestinal (GI) amyloid was prevalent, and macroscopically visible amyloidotic lesions were present in nine of 10 patients who underwent GI endoscopy. All symptomatic ALys individuals had hepatic amyloid. Four patients received orthotopic liver transplants (OLT), three for spontaneous hepatic rupture and one case, who had extensive hepatic amyloid and a strong family history of hepatic rupture, pre-emptively. All of the liver grafts were functioning at censor 1.7, 5.8, 9.0 and 11.0 years after OLT. Five patients had progressive amyloidotic renal dysfunction culminating in end-stage renal failure, three of whom underwent renal transplantation (RTx). There was no evidence of renal allograft dysfunction at censor 6.6, 1.8 and 0.8 years after RTx.
  
  
  CONCLUSIONS
  Lysozyme amyloidosis is a disease of the GI tract, liver and kidneys, which has a slow natural history. There was a clear family history in all cases within this cohort, demonstrating a high clinical penetrance in the presence of an amyloidogenic lysozyme mutation. There is currently no amyloid-specific therapy for the condition which is managed symptomatically. OLT and RTx appear to be successful treatments for patients with liver rupture or end-stage renal disease, respectively, with excellent outcomes in terms of medium-term graft function and patient survival.
authors: National Amyloidosis Centre, Centre for Amyloidosis & Acute Phase Proteins, Department of Medicine, Royal Free Campus, University College London Medical School, London, UK.
authors: P T
authors: PT
authors: Sattianayagam
authors: S D J
authors: SD
authors: Gibbs
authors: D
authors: D
authors: Rowczenio
authors: J H
authors: JH
authors: Pinney
authors: A D
authors: AD
authors: Wechalekar
authors: J A
authors: JA
authors: Gilbertson
authors: P N
authors: PN
authors: Hawkins
authors: H J
authors: HJ
authors: Lachmann
authors: J D
authors: JD
authors: Gillmore
mesh_terms: D000328:Adult; D000368:Aged; D028226:Amyloidosis, Familial / Q000000981:diagnostic imaging / Q000235:genetics* / Q000401:mortality / Q000601:surgery*; D002648:Child; D005260:Female; D005767:Gastrointestinal Diseases / Q000235:genetics; D006801:Humans; D007676:Kidney Failure, Chronic / Q000601:surgery; D016030:Kidney Transplantation; D008107:Liver Diseases / Q000601:surgery; D016031:Liver Transplantation; D008206:Lymphatic Diseases / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009113:Muramidase / Q000235:genetics*; D009154:Mutation; D010438:Peptic Ulcer Hemorrhage / Q000235:genetics; D010641:Phenotype; D011693:Purpura / Q000235:genetics; D011877:Radionuclide Imaging; D012189:Retrospective Studies; D012422:Rupture, Spontaneous / Q000235:genetics; D000683:Serum Amyloid P-Component / Q000378:metabolism; D012859:Sjogren's Syndrome / Q000235:genetics; D016019:Survival Analysis; D006113:United Kingdom
chemical_list: D000683:Serum Amyloid P-Component; D009113:Muramidase