title: Copper- and iron-rich matrices in hepatocellular lipofuscin particles of a young male patient: diagnostic ultrastructures for Wilson disease.
abstract: A 17-year-old male patient appeared with the biochemical liver damage associated with hypoceruloplasminemia and mild iron overload. Genetic analysis identified a compound heterozygosity of ATP7B responsible for the primary copper toxicosis of Wilson disease without mutations in HFE. A liver specimen consisted of cirrhotic nodules of large-sized hepatocytes with fatty change and those of fat-free small-sized hepatocytes. Histochemically, iron was distributed diffusely in the small-sized hepatocytes, while copper grains appeared in a few of the hepatocytes near the fibrous bands. X-ray microanalysis on the liver tissue fixed with a 0.1% osmium tetroxide solution and embedded in epoxy resin disclosed (1) complex formation of copper with sulfur, and iron with phosphorus in the hepatocyte lipofuscin particles, (2) intraparticle localization of the cuprothionein in the less dense matrix and ferric proteins in the dense matrix, and (3) high affinity of the cuprothionein to lead staining. Considering the fact that ceruloplasmin is the major ferroxidase essential for iron efflux, iron deposits in the hypoceruloplasminemic patients with Wilson disease are not a complication, but a natural event. This study disclosed for the first time the diagnostic ultrastructures of Wilson disease, which might represent different detoxification processes to the reactive metals of copper and iron.
authors.affiliation: Department of Pharmacy, University Hospital of Graduate School of Medicine, Kanazawa University, Kanazawa, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Motonishi
authors.forename: Hisao
authors.initials: H
authors.lastname: Hayashi
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Fujita
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Okada
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Kusakabe
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ito
authors.forename: Kenichi
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Toshio
authors.initials: T
authors.lastname: Ueno
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000293:Adolescent; D027682:Cation Transport Proteins / Q000235:genetics; D002570:Ceruloplasmin / Q000032:analysis; D003300:Copper / Q000032:analysis* / Q000378:metabolism; D000073840:Copper-Transporting ATPases; D004577:Electron Probe Microanalysis; D000071020:Hemochromatosis Protein; D022781:Hepatocytes / Q000737:chemistry / Q000648:ultrastructure*; D006527:Hepatolenticular Degeneration / Q000378:metabolism / Q000473:pathology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006651:Histocytochemistry; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000648:ultrastructure*; D007501:Iron / Q000032:analysis* / Q000378:metabolism; D008062:Lipofuscin / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D046529:Microscopy, Electron, Transmission; D009154:Mutation
chemical_list: D027682:Cation Transport Proteins; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008062:Lipofuscin; D008565:Membrane Proteins; D003300:Copper; D007501:Iron; D002570:Ceruloplasmin; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases