Primary iron overload with inappropriate hepcidin expression in V162del ferroportin disease

被引:47
作者
Zoller, H
McFarlane, I
Theurl, I
Stadlmann, S
Nemeth, E
Oxley, D
Ganz, T
Halsall, DJ
Cox, TM
Vogel, W
机构
[1] Univ Cambridge, Dept Med, Addenbrookes Hosp, Cambridge CB2 2QQ, England
[2] Innsbruck Med Univ, Clin Div Gastroenterol & Hepatol, Innsbruck, Austria
[3] Innsbruck Med Univ, Clin Div Gen Internal Med, Innsbruck, Austria
[4] Cambridge Univ Hosp NHS Trust, Dept Clin Biochem, Cambridge, England
[5] Innsbruck Med Univ, Dept Pathol, Innsbruck, Austria
[6] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90024 USA
[7] Babraham Inst, Cambridge, England
基金
英国惠康基金;
关键词
D O I
10.1002/hep.20775
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Ferroportin disease (hemochromatosis type 4) is a recently recognized disorder of human iron metabolism, characterized by iron deposition in macrophages, including Kupfer cells. Mutations in the gene encoding ferroportin 1, a cellular iron exporter, are responsible for this iron storage disease, inherited as an autosomal dominant trait. We present clinical, histopathological, and radiological findings in a family with the most common ferroportin mutation, V162del. In the index case, the disorder is characterized by abundant deposition of hemosiderin in all tissues investigated (mesenteric lymph node, liver, gastric and duodenal mucosa, and also in squamous cell carcinoma of the lung). The radiological findings indicated the presence of excess iron in bone marrow and spleen. Despite a significant burden of iron, no features of chronic liver disease were found in affected members of the family, including individuals aged up to 80 years. Hyperferritinemia greater than 1,000 mu g/L was a penetrant biochemical finding before the second decade in life and was associated with significantly increased serum concentrations of pro-hepcidin that correlated positively with urinary hepcidin concentrations. In conclusion, the systemic iron burden in ferroportin disease is not a sufficient cause for chronic liver disease. In patients with most, but not all, ferroportin mutations, retention of iron in macrophages of the liver and other organs may protect against damage to parenchymal cells. Finally, macrophage iron storage in ferroportin disease is associated with elevated serum pro-hepcidin levels.
引用
收藏
页码:466 / 472
页数:7
相关论文
共 43 条
  • [11] Iron overload in Africans and African-Americans and a common mutation in the SCL40A1 (ferroportin 1) gene
    Gordeuk, VR
    Caleffi, A
    Corradini, E
    Ferrara, F
    Jones, RA
    Castro, O
    Onyekwere, O
    Kittles, R
    Pignatti, E
    Montosi, G
    Garuti, C
    Gangaidzo, IT
    Gomo, ZAR
    Moyo, VM
    Rouault, TA
    MacPhail, P
    Pietrangelo, A
    [J]. BLOOD CELLS MOLECULES AND DISEASES, 2003, 31 (03) : 299 - 304
  • [12] Molecular analyses of patients with hyperferritinemia and normal serum iron values reveal both L ferritin IRE and 3 new ferroportin (slc11A3) mutations
    Hetet, G
    Devaux, I
    Soufir, N
    Grandchamp, B
    Beaumont, C
    [J]. BLOOD, 2003, 102 (05) : 1904 - 1910
  • [13] Novel mutation in ferroportin 1 gene is associated with autosomal dominant iron overload
    Jouanolle, AM
    Douabin-Gicquel, V
    Halimi, C
    Loréal, O
    Fergelot, P
    Delacour, T
    de Lajarte-Thirouard, AS
    Turlin, B
    Le Gall, JY
    Cadet, E
    Rochette, J
    David, V
    Brissot, P
    [J]. JOURNAL OF HEPATOLOGY, 2003, 39 (02) : 286 - 289
  • [14] Pro-hepcidin: expression and cell specific localisation in the liver and its regulation in hereditary haemochromatosis, chronic renal insufficiency, and renal anaemia
    Kulaksiz, H
    Gehrke, SG
    Janetzko, A
    Rost, D
    Bruckner, T
    Kallinowski, B
    Stremmel, W
    [J]. GUT, 2004, 53 (05) : 735 - 743
  • [15] The iron-regulatory peptide hormone hepcidin: expression and cellular localization in the mammalian kidney
    Kulaksiz, H
    Theilig, F
    Bachmann, S
    Gehrke, SG
    Rost, D
    Janetzko, A
    Cetin, Y
    Stremmel, W
    [J]. JOURNAL OF ENDOCRINOLOGY, 2005, 184 (02) : 361 - 370
  • [16] Severe hemochromatosis in a Portuguese family associated with a new mutation in the 5'-UTR of the HAMP gene
    Matthes, T
    Aguilar-Martinez, P
    Pizzi-Bosman, L
    Darbellay, R
    Rubbia-Brandt, L
    Giostra, E
    Michel, M
    Ganz, T
    Beris, P
    [J]. BLOOD, 2004, 104 (07) : 2181 - 2183
  • [17] The SLC40 basolateral iron transporter family (IREG1/ferroportin/MTP1)
    McKie, AT
    Barlow, DJ
    [J]. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 2004, 447 (05): : 801 - 806
  • [18] Digenic inheritance of mutations in HAMP and HFE results in different types of haemochromatosis
    Merryweather-Clarke, AT
    Cadet, E
    Bomford, A
    Capron, D
    Viprakasit, V
    Miller, A
    McHugh, PJ
    Chapman, RW
    Pointon, JJ
    Wimhurst, VLC
    Livesey, KJ
    Tanphaichitr, V
    Rochette, J
    Robson, KJH
    [J]. HUMAN MOLECULAR GENETICS, 2003, 12 (17) : 2241 - 2247
  • [19] Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene
    Montosi, G
    Donovan, A
    Totaro, A
    Garuti, C
    Pignatti, E
    Cassanelli, S
    Trenor, CC
    Gasparini, P
    Andrews, NC
    Pietrangelo, A
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2001, 108 (04) : 619 - 623
  • [20] Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein
    Nemeth, E
    Valore, EV
    Territo, M
    Schiller, G
    Lichtenstein, A
    Ganz, T
    [J]. BLOOD, 2003, 101 (07) : 2461 - 2463