title: Clinical and pathologic characteristics of hereditary apolipoprotein A-I amyloidosis in Ireland.
abstract: OBJECTIVE
  Apolipoprotein A-I amyloidosis is a rare, autosomal dominant disorder characterized by progressive accumulation of amyloid fibrils in tissues, leading to renal and hepatic disease. We describe the clinical manifestations and pathologic features of kidney disease in three Irish families.
  
  
  METHODS
  This observational study examines all known cases of chronic kidney disease due to hereditary apolipoprotein A-I amyloidosis in Ireland. Patients were identified by physician interview. In all of the affected individuals the disease was caused by the Gly26Arg heterozygous mutation. Immunohistochemistry confirmed that amyloid deposits were composed of apolipoprotein A-I fibrils. Family trees and clinical data were obtained via analysis of patient medical records.
  
  
  RESULTS
  The vast majority of affected cases had demonstrable kidney disease, with variable liver disease. Renal disease most commonly manifested as slowly progressive renal impairment with mild proteinuria. In one kindred, a severe, debilitating peripheral neuropathy was common among affected family members. Histology demonstrated tubulointerstitial fibrosis with amyloid deposition in the medulla. There was very high penetrance within affected families. Of five patients who were transplanted, one transplant was lost after 5 years due to recurrent disease. One patient died from sepsis shortly after transplant.
  
  
  CONCLUSIONS
  Hereditary apolipoprotein A-I amyloidosis is characterized by slowly progressive renal disease. Amyloid is deposited in the renal medulla highlighting the need to examine the medulla on renal biopsy. Overall, kidney transplantation conferred a survival advantage.
authors.affiliation: Department of Nephrology and Transplantation, Beaumont Hospital, Dublin 9, Ireland. caroltraynor@beaumont.ie
authors.forename: Carol A
authors.initials: CA
authors.lastname: Traynor
authors.forename: Donal
authors.initials: D
authors.lastname: Tighe
authors.forename: Frank J
authors.initials: FJ
authors.lastname: O'Brien
authors.forename: Sean F
authors.initials: SF
authors.lastname: Leavey
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Dorman
authors.forename: Mark D
authors.initials: MD
authors.lastname: Denton
authors.forename: Colm
authors.initials: C
authors.lastname: Magee
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Conlon
mesh_terms: D000328:Adult; D000368:Aged; D000682:Amyloid / Q000235:genetics* / Q000378:metabolism; D028226:Amyloidosis, Familial / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D016632:Apolipoprotein A-I / Q000172:deficiency / Q000235:genetics*; D001706:Biopsy; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006579:Heterozygote; D006801:Humans; D007494:Ireland; D007668:Kidney / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011507:Proteinuria / Q000235:genetics / Q000378:metabolism; D012008:Recurrence; D051436:Renal Insufficiency, Chronic / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C505693:APOA1 protein, human; D000682:Amyloid; D016632:Apolipoprotein A-I
keywords: amyloid; apolipoprotein; hereditary; kidney transplantation