Liver Biopsy Discloses a New Apolipoprotein A-I Hereditary Amyloidosis in Several Unrelated Italian Families

Laura Obici, Giovanni Palladini, Sofia Giorgetti, Vittorio Bellotti, Gina Gregorini, Eloisa Arbustini, Laura Verga, Sabrina Marciano, Simona Donadei, Vittorio Perfetti, Laura Calabresi, Cesare Bergonzi, Francesco Scolari, Giampaolo Merlini

Research output: Contribution to journalArticlepeer-review


Background & Aims: Hereditary systemic amyloidoses are autosomal dominant, late-onset disorders caused by mutations in the genes for a group of plasma proteins including transthyretin, lysozyme, fibrinogen Aα chain, gelsolin, apolipoprotein A-I, and apolipoprotein A-II. We investigated both phenotypic and genotypic aspects of apolipoprotein A-I amyloidosis unexpectedly disclosed by liver biopsy in 13 unrelated individuals with asymptomatic, persistent elevation of alkaline phosphatase and γ-glutamyltransferase levels. Methods: Immunoelectron microscopy was used for in situ characterization of amyloid deposits on liver biopsy specimens. Mutation analysis was performed by sequencing of the apolipoprotein A-I gene in all patients. Wild-type/variant apolipoprotein A-I ratio in plasma high-density lipoproteins was assessed by a peptide mass fingerprinting approach after purification of total apolipoprotein A-I of 2 patients. Results: Family history was informative in 5 cases. Renal failure developed in 9 cases. Hypogonadism due to testicular involvement was observed. Amyloid fibrils specifically stained with anti-apolipoprotein A-I antibody. A novel (Leu75Pro) heterozygous mutation in the apolipoprotein A-I gene was present in affected individuals but not in controls. Variant apolipoprotein A-I was about 10% of the total protein in high-density lipoproteins. Conclusions. The high number of individuals with apparently sporadic disease might reflect widespread occurrence of this mutation in the population and a milder phenotype of this variant compared with other apolipoprotein A-I amyloidogenic mutants. These findings suggest that specific staining for amyloid should be performed on liver biopsy of individuals with asymptomatic chronic elevation of alkaline phosphatase and γ-glutamyltransferase levels.

Original languageEnglish
Pages (from-to)1416-1422
Number of pages7
Issue number5
Publication statusPublished - May 2004

ASJC Scopus subject areas

  • Gastroenterology


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