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Research Article

Clinical Perspectives on Hereditary Hemochromatosis

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Pages 451-484 | Published online: 01 Jan 2008

REFERENCES

  • J K Olynyk, T G St Pierre, R S Britton, E M Brunt, and B R Bacon. (2005). Duration of hepatic iron exposure increases the risk of significant fibrosis in hereditary hemochromatosis: a new role for magnetic resonance imaging. Am J Gastroenterol 100:837–841.
  • P C Adams. (2006). Review article: the modern diagnosis and management of haemochromatosis. Aliment Pharmacol Ther 23:1681–1691.
  • C W Siah, D Trinder, and J K Olynyk. (2005). Iron overload. Clin Chim Acta 358:24–36.
  • A Bomford. (2002). Genetics of haemochromatosis. Lancet 360:1673–1681.
  • J N Feder, A Gnirke, W Thomas, Z Tsuchihashi, D A Ruddy, A Basava, F Dormishian, R Domingo, M C Ellis, A Fullan, L M Hinton, N L Jones, B E Kimmel, G S Kronmal, P Lauer, V K Lee, D B Loeb, F A Mapa, E McClelland, N C Meyer, G A Mintier, N Moeller, T Moore, E Morikang, C E Prass, L Quintana, S M Starnes, R C Schatzman, K J Brunke, D T Drayna, N J Risch, B R Bacon, and R K Wolff. (1996). A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 13:399–408.
  • A CG Chua, R M Graham, D Trinder, and J K Olynyk. (2007). The regulation of cellular iron metabolism. Crit Rev Clin Lab Sci 44:413–459.
  • S Parkkila, A Waheed, R S Britton, J N Feder, Z Tsuchihashi, R C Schatzman, B R Bacon, and W S Sly. (1997). Immunohistochemistry of HLA-H, the protein defective in patients with hereditary hemochromatosis, reveals unique pattern of expression in gastrointestinal tract. Proc Natl Acad Sci USA 94:2534–2539.
  • J M Bastin, M Jones, C A O'Callaghan, L Schimanski, D Y Mason, and A RM Townsend. (1998). Kupffer cell staining by an HFE-specific monoclonal antibody: implications for hereditary haemochromatosis. Br J Haematol 103:931–941.
  • A Krause, S Neitz, H J Magert, A Schulz, W G Forssmann, P Schulz-Knappe, and K Adermann. (2000). LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity. FEBS Lett 480:147–150.
  • C H Park, E V Valore, A J Waring, and T Ganz. (2001). Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem 276:7806–7810.
  • H Kawabata, S Yang, T Hirama, P T Vuong, S Kawano, A F Gombart, and H P Koeffler. (1999). Molecular cloning of transferrin receptor 2—A new member of the transferrin receptor-like family. J Biol Chem 274:20826–20832.
  • A P West, M J Bennett, V M Sellers, N C Andrews, C A Enns, and P J Bjorkman. (2000). Comparison of the interactions of transferrin receptor and transferrin receptor 2 with transferrin and the hereditary hemochromatosis protein HFE. J Biol Chem 275:38135–38138.
  • A D Robb, M Ericsson, and M Wessling-Resnick. (2004). Transferrin receptor 2 mediates a biphasic pattern of transferrin uptake associated with ligand delivery to multivesicular bodies. Am J Physiol Cell Physiol 287:C1769–C1775.
  • J Krijt, M Vokurka, K T Chang, and E Necas. (2004). Expression of Rgmc, the murine ortholog of hemojuvelin gene, is modulated by development and inflammation, but not by iron status or erythropoietin. Blood 104:4308–4310.
  • J L Babitt, F W Huang, D M Wrighting, Y Xia, Y Sidis, T A Samad, J A Campagna, R T Chung, A L Schneyer, C J Woolf, N C Andrews, and H Y Lin. (2006). Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet 38:531–539.
  • E Nemeth. (2008). Iron regulation and erythropoiesis. Curr Opin Hematol 15:169–175.
  • S Abboud, and D J Haile. (2000). A novel mammalian iron-regulated protein involved in intracellular iron metabolism. J Biol Chem 275:19906–19912.
  • A Donovan, A Brownlie, Y Zhou, J Shepard, S J Pratt, J Moynihan, B H Paw, A Drejer, B Barut, A Zapata, T C Law, C Brugnara, P D Kingsley, J Palis, M D Fleming, N C Andrews, and L I Zon. (2000). Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter. Nature 403:776–781.
  • A T McKie, P Marciani, A Rolfs, K Brennan, K Wehr, D Barrow, S Miret, A Bomford, T J Peters, F Farzaneh, M A Hediger, M W Hentze, and R J Simpson. (2000). A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation. Mol Cell 5:299–309.
  • E Nemeth, M S Tuttle, J Powelson, M B Vaughn, A Donovan, D M Ward, T Ganz, and J Kaplan. (2004). Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306:2090–2093.
  • J K Olynyk, D J Cullen, S Aquilia, E Rossi, L Summerville, and L W Powell. (1999). A population-based study of the clinical expression of the hemochromatosis gene. N Engl J Med 341:718–724.
  • L W Powell, V N Subramaniam, and T R Yapp. (2000). Haemochromatosis in the new millennium. J Hepatol 32:48–62.
  • L W Powell, J L Dixon, G A Ramm, D M Purdie, D J Lincoln, G J Anderson, V N Subramaniam, D G Hewett, J W Searle, L M Fletcher, D H Crawford, H Rodgers, K J Allen, J A Cavanaugh, and M L Bassett. (2006). Screening for hemochromatosis in asymptomatic subjects with or without a family history. Arch Intern Med 166:294–301.
  • P Brissot, Y Hitadenercy, Y Pawlotsky, M Simon, and M Bourel. (1977). Biology of idiopathic hemochromatosis—Without quantitative hormone determination. Rev Med 18:835.
  • M Simon, M Bourel, B Genetet, and R Fauchet. (1977). Idiopathic hemochromatosis. Demonstration of recessive transmission and early detection by Family HLA typing. N Engl J Med 297:1017–1021.
  • A Pietrangelo. (2004). Hereditary hemochromatosis—A new look at an old disease. N Engl J Med 350:2383–2397.
  • E C Jazwinska, L M Cullen, F Busfield, W R Pyper, S I Webb, L W Powell, C P Morris, and T P Walsh. (1996). Haemochromatosis and HLA-H. Nat Genet 14:249–251.
  • P Brissot, R Moirand, A M Jouanolle, D Guyader, J Y Le Gall, Y Deugnier, and V David. (1999). A genotypic study of 217 unrelated probands diagnosed as “genetic hemochromatosis” on “classical” phenotypic criteria. J Hepatol 30:588–593.
  • (1997). The UK Haemochromatosis Consortium W.M. A simple genetic test identifies 90% of UK patients with haemochromatosis. The UK Haemochromatosis Consortium. Gut 41:841–844.
  • A Piperno, M Sampietro, A Pietrangelo, C Arosio, L Lupica, G Montosi, A Vergani, M Fraquelli, D Girelli, P Pasquero, A Roetto, P Gasparini, S Fargion, D Conte, and C Camaschella. (1998). Heterogeneity of hemochromatosis in Italy. Gastroenterology 114:996–1002.
  • A T Merryweather-Clarke, J J Pointon, J D Shearman, and K J Robson. (1997). Global prevalence of putative haemochromatosis mutations. J Med Genet 34:275–278.
  • P C Adams, D M Reboussin, J C Barton, C E McLaren, J H Eckfeldt, G D McLaren, F W Dawkins, R T Acton, E L Harris, V R Gordeuk, C Leiendecker-Foster, M Speechley, B M Snively, J L Holup, E Thomson, and P Sholinsky. (2005). Hemochromatosis and iron-overload screening in a racially diverse population. N Engl J Med 352:1769–1778.
  • C Mura, O Raguenes, and C Ferec. (1999). HFE mutations analysis in 711 hemochromatosis probands: evidence for S65C implication in mild form of hemochromatosis. Blood 93:2502–2505.
  • J N de Villiers, R Hillermann, L Loubser, and M J Kotze. (1999). Spectrum of mutations in the HFE gene implicated in haemochromatosis and porphyria. Hum Mol Genet 8:1517–1522.
  • J C Barton, B E Rothenberg, L F Bertoli, and R T Acton. (1999). Diagnosis of hemochromatosis in family members of probands: a comparison of phenotyping and HFE genotyping. Genet Med 1:89–93.
  • A Salvioni, R Mariani, C Oberkanins, A Moritz, V Mauri, S Pelucchi, A Riva, C Arosio, P Cerutti, and A Piperno. (2003). Prevalence of C282Y and E168X HFE mutations in an Italian population of Northern European ancestry. Haematologica 88:250–255.
  • A Pietrangelo. (2005). Non-HFE hemochromatosis. Semin Liver Dis 25:450–460.
  • C Camaschella. (1998). Juvenile haemochromatosis. Baillieres Clinical Gastroenterology 12:227–235.
  • S R Rivard, C Lanzara, D Grimard, M Carella, H Simard, R Ficarella, R Simard, A P D'Adamo, C Ferec, C Camaschella, C Mura, A Roetto, M De Braekeleer, L Bechner, and P Gasparini. (2003). Juvenile hemochromatosis locus maps to chromosome 1q in a French Canadian population. Eur J Hum Genet 11:585–589.
  • G Papanikolaou, M E Samuels, E H Ludwig, M LE MacDonald, P L Franchini, M P Dube, L Andres, J MacFarlane, N Sakellaropoulos, M Politou, E Nemeth, J Thompson, J K Risler, C Zaborowska, R Babakaiff, C C Radomski, T D Pape, O Davidas, J Christakis, P Brissot, G Lockitch, T Ganz, M R Hayden, and Y P Goldberg. (2004). Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis. Nat Genet 36:77–82.
  • A Roetto, G Papanikolaou, M Politou, F Alberti, D Girelli, J Christakis, D Loukopoulos, and C Camaschella. (2003). Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis. Nat Genet 33:21–22.
  • C Camaschella, A Roetto, A Cali, M De Gobbi, G Garozzo, M Carella, N Majorano, A Totaro, and P Gasparini. (2000). The gene TFR2 is mutated in a new type of haemochromatosis mapping to 7q22. Nat Genet 25:14–15.
  • M De Gobbi, M R Barilaro, G Garozzo, L Sbaiz, F Alberti, and C Camaschella. (2001). TFR2 Y250X mutation in Italy. Br J Haematol 114:243–244.
  • A Roetto, A Totaro, A Piperno, A Piga, F Longo, G Garozzo, A Cali, M De Gobbi, P Gasparini, and C Camaschella. (2001). New mutations inactivating transferrin receptor 2 in hemochromatosis type 3. Blood 97:2555–2560.
  • D Girelli, C Bozzini, A Roetto, F Alberti, F Daraio, R Colombari, O Olivieri, R Corrocher, and C Camaschella. (2002). Clinical and pathologic findings in hemochromatosis type 3 due to a novel mutation in transferrin receptor 2 gene. Gastroenterology 122:1295–1302.
  • A Mattman, D Huntsman, G Lockitch, S Langlois, N Buskard, D Ralston, Y Butterfield, P Rodrigues, S Jones, G Porto, M Marra, M De Sousa, and G Vatcher. (2002). Transferrin receptor 2 (TfR2) and HFE mutational analysis in non-C282Y iron overload: identification of a novel TfR2 mutation. Blood 100:1075–1077.
  • G LeGac, F Mons, S Jacolot, V Scotet, C Ferec, and T Frebourg. (2004). Early onset hereditary hemochromatosis resulting from a novel TFR2 gene nonsense mutation (R105X) in two siblings of north French descent. Br J Haematol 125:674–678.
  • C Koyama, S Wakusawa, H Hayashi, R Suzuki, M Yano, K Yoshioka, M Kozuru, Y Takayamam, T Okada, and H Mabuchi. (2005). Two novel mutations, L490R and V561X, of the transferrin receptor 2 gene in Japanese patients with hemochromatosis. Haematologica 90:302–307.
  • H Kawabata, R E Fleming, D Gui, S Y Moon, T Saitoh, J O'Kelly, Y Umehara, Y Wano, J W Said, and H P Koeffler. (2005). Expression of hepcidin is down-regulated in TfR2 mutant mice manifesting a phenotype of hereditary hemochromatosis. Blood 105:376–381.
  • S F Drake, E H Morgan, C E Herbison, R Delima, R M Graham, A CG Chua, P J Leedman, R E Fleming, B R Bacon, J K Olynyk, and D Trinder. (2007). Iron absorption and hepatic iron uptake are increased in a transferrin receptor 2 (Y245X) mutant mouse model of hemochromatosis type 3. Am J Physiol Gastrointest Liver Physiol 292:G323–G328.
  • E Nemeth, A Roetto, G Garozzo, T Ganz, and C Camaschella. (2005). Hepcidin is decreased in TFR2 hemochromatosis. Blood 105:1803–1806.
  • A M Jouanolle, V Douabin-Gicquel, C Halimi, O Loréal, P Fergelot, T Delacour, A S de Lajarte-Thirouard, B Turlin, J Y Le Gall, E Cadet, J Rochette, V David, and P Brissot. (2003). Novel mutation in ferroportin 1 gene is associated with autosomal dominant iron overload. J Hepatol 39:286–289.
  • G Montosi, A Donovan, A Totaro, C Garuti, E Pignatti, S Cassanelli, C C Trenor, P Gasparini, N C Andrews, and A Pietrangelo. (2001). Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene. J Clin Invest 108:619–623.
  • O T Njajou, N Vaessen, M Joosse, B Berghuis, J WF van Dongen, M H Breuning, P Snijders, W PF Rutten, L A Sandkuijl, B A Oostra, C M van Duijn, and P Heutink. (2001). A mutation in SLC11A3 is associated with autosomal dominant hemochromatosis. Nat Genet 28:213–214.
  • K E Arden, D F Wallace, J L Dixon, L Summerville, J W Searle, G J Anderson, G A Ramm, L W Powell, and V N Subramaniam. (2003). A novel mutation in ferroportin1 is associated with haemochromatosis in a Solomon Islands patient. Gut 52:1215–1217.
  • G Hetet, I Devaux, N Soufir, B Grandchamp, and C Beaumont. (2003). Molecular analyses of patients with hyperferritinemia and normal serum iron values reveal both L ferritin IRE and 3 new ferroportin (slc11A3) mutations. Blood 102:1904–1910.
  • E Beutler, J C Barton, V J Felitti, T Gelbart, C West, P L Lee, J Waalen, and C Vulpe. (2003). Ferroportin 1 (SCL40A1) variant associated with iron overload in African-Americans. Blood Cells Mol Dis 31:305–309.
  • V Bach, A Remacha, A Altes, M J Barcelo, M A Molina, and M Baiget. (2005). Autosomal dominant hereditary hemochromatosis associated with two novel Ferroportin 1 mutations in Spain. Blood Cells Mol Dis 36:41–45.
  • D F Wallace, P Browett, P Wong, H Kua, R Ameratunga, and V N Subramaniam. (2005). Identification of ferroportin disease in the Indian subcontinent. Gut 54:567–568.
  • V Devalia, K Carter, A P Walker, S J Perkins, M Worwood, A May, and J S Dooley. (2002). Autosomal dominant reticuloendothelial iron overload associated with a 3-base pair deletion in the ferroportin 1 gene (SLC11A3). Blood 100:695–697.
  • R L Sham, P D Phatak, C West, P Lee, C Andrews, and E Beutler. (2005). Autosomal dominant hereditary hemochromatosis associated with a novel ferroportin mutation and unique clinical features. Blood Cells Mol Dis 34:157–161.
  • L M Schimanski, H Drakesmith, A T Merryweather-Clarke, V Viprakasit, J P Edwards, E Sweetland, J M Bastin, D Cowley, Y Chinthammitr, K J Robson, and A R Townsend. (2005). In vitro functional analysis of human ferroportin (FPN) and hemochromatosis-associated FPN mutations. Blood 105:4096–4102.
  • N F Olivieri, and G M Brittenham. (1997). Iron-chelating therapy and the treatment of thalassemia. Blood 89:739–761.
  • P Pootrakul, K Kitcharoen, P Yansukon, P Wasi, S Fucharoen, P Charoenlarp, G Brittenham, M J Pippard, and C A Finch. (1988). The effect of erythroid hyperplasia on iron balance. Blood 71:1124–1129.
  • N F Olivieri. (1999). The beta-thalassemias. N Engl J Med 341:99–109.
  • E Nemeth, and T Ganz. (2006). Hepcidin and iron-loading anemias. Haematologica 91:727–732.
  • R Origa, R Galanello, T Ganz, N Giagu, L Maccioni, G Faa, and E Nemeth. (2007). Liver iron concentrations and urinary hepcidin in beta-thalassemia. Haematologica 92:583–588.
  • G M Brittenham, P M Griffith, A W Nienhuis, C E McLaren, N S Young, E E Tucker, C J Allen, D E Farrell, and J W Harris. (1994). Efficacy of deferoxamine in preventing complications of iron overload in patients with thalassemia major. N Engl J Med 331:567–573.
  • N Hanspeter. (2007). Iron chelation, quo vadis?. Curr Opin Chem Biol 11:419–423.
  • D J Roberts, D Rees, J Howard, C Hyde, P Alderson, and S Brunskill. (2005). Desferrioxamine mesylate for managing transfusional iron overload in people with transfusion-dependent thalassaemia. Cochrane Database Syst Rev 4: CD004450
  • E J Neufeld. (2006). Oral chelators deferasirox and deferiprone for transfusional iron overload in thalassemia major: new data, new questions. Blood 107:3436–3441.
  • W T Lindsey, and B R Olin. (2007). Deferasirox for transfusion-related iron overload: A clinical review. Clin Ther 29:2154–2166.
  • C Hershko. (2007). Iron loading and its clinical implications. Am J Hematol 82:1147–1148.
  • L PH Yang, S J Keam, and G M Keating. (2007). Deferasirox—A review of its use in the management of transfusional chronic iron overload. Drugs 67:2211–2230.
  • G Papanikolaou, M Tzilianos, J I Christakis, D Bogdanos, K Tsimirika, J MacFarlane, Y P Goldberg, N Sakellaropoulos, T Ganz, and E Nemeth. (2005). Hepcidin in iron overload disorders. Blood 105:4103–4105.
  • K Adamsky, O Weizer, N Amariglio, L Breda, A Harmelin, S Rivella, E Rachmilewitz, and G Rechavi. (2004). Decreased hepcidin mRNA expression in thalassemic mice. Br J Haematol 124:123–124.
  • T H Bothwell. (1995). Overview and mechanisms of iron regulation. Nutr Rev 53:237–245.
  • V Gordeuk, J Mukiibi, Sj Hasstedt, W Samowitz, C Q Edwards, G West, S Ndambire, J Emmanual, N Nkanza, Z Chapanduka, M Randall, P Boone, P Romano, R W Martell, T Yamashita, P Effler, and G Brittenham. (1992). Iron overload in Africa. Interaction between a gene and dietary iron content. N Engl J Med 326:95–100.
  • B Brink, P Disler, S Lynch, P Jacobs, R Charlton, and T Bothwell. (1976). Patterns of iron storage in dietary iron overload and idiopathic hemochromatosis. J Lab Clin Med 88:725–731.
  • L McNamara, A P MacPhail, V R Gordeuk, S J Hasstedt, and T Rouault. (1998). Is there a link between African iron overload and the described mutations of the hereditary haemochromatosis gene?. Br J Haematol 102:1176–1178.
  • V R Gordeuk, A Caleffi, E Corradini, F Ferrara, R A Jones, O Castro, O Onyekwere, R Kittles, E Pignatti, G Montosi, C Garuti, I T Gangaidzo, Z A Gomo, V M Moyo, T A Rouault, P MacPhail, and A Pietrangelo. (2003). Iron overload in Africans and African-Americans and a common mutation in the SCL40A1 (ferroportin 1) gene. Blood Cells Mol Dis 31:299–304.
  • L McNamara, V R Gordeuk, and A P MacPhail. (2005). Ferroportin (Q248H) mutations in African families with dietary iron overload. J Gastroenterol Hepatol 20:1855–1858.
  • J Ludwig, E Hashimoto, M K Porayko, T P Moyer, and W P Baldus. (1997). Hemosiderosis in cirrhosis: a study of 447 native livers. Gastroenterology 112:882–888.
  • D Trinder, O T Ayonrinde, and J K Olynyk. (2008). HCV, iron, and oxidative stress: the new choreography of hepcidin. Gastroenterology 134:348–351.
  • G A Ramm, and R G Ruddell. (2005). Hepatotoxicity of iron overload: mechanisms of iron-induced hepatic fibrogenesis. Semin Liver Dis 25:433–449.
  • R G Batey, and R Johnston. (1993). Effects of alcohol, carbon-tetrachloride, and choline deficiency on iron-metabolism in the rat. Alcohol Clin Exp Res 17:931–934.
  • J K Olynyk, K R Reddy, A M Di Bisceglie, L J Jeffers, T I Parker, J L Radick, E R Schiff, and B R Bacon. (1995). Hepatic iron concentration as a predictor of response to interferon alfa therapy in chronic hepatitis C. Gastroenterology 108:1104–1109.
  • A M Di Bisceglie, H L Bonkovsky, S Chopra, S Flamm, R K Reddy, N Grace, P Killenberg, C Hunt, C Tamburro, A S Tavill, R Ferguson, E Krawitt, B Banner, and B R Bacon. (2000). Iron reduction as an adjuvant to interferon therapy in patients with chronic hepatitis C who have previously not responded to interferon: a multicenter, prospective, randomized, controlled trial. Hepatology 32:135–138.
  • J Kato, K Fujikawa, M Kanda, N Fukuda, K Sasaki, T Takayama, M Kobune, K Takada, R Takimoto, H Hamada, T Ikeda, and Y Niitsu. (2001). A mutation, in the iron-responsive element of H ferritin mRNA, causing autosomal dominant iron overload. Am J Hum Genet 69:191–197.
  • P F Whitington. (2007). Neonatal hemochromatosis: a congenital alloimmune hepatitis. Semin Liver Dis 27:243–250.
  • N Goya, S Miyazaki, S Kodate, and B Ushio. (1972). A family of congenital atransferrinemia. Blood 40:239–245.
  • E Beutler, T Gelbart, P Lee, R Trevino, M A Fernandez, and V F Fairbanks. (2000). Molecular characterization of a case of atransferrinemia. Blood 96:4071–4074.
  • Z L Harris, Y Takahashi, H Miyajima, M Serizawa, R T MacGillivray, and J D Gitlin. (1995). Aceruloplasminemia: molecular characterization of this disorder of iron metabolism. Proc Natl Acad Sci USA 92:2539–2543.
  • N E Hellman, M Schaefer, S Gehrke, P Stegen, W J Hoffman, J D Gitlin, and W Stremmel. (2000). Hepatic iron overload in aceruloplasminaemia. Gut 47:858–860.
  • E M Becker, J M Greer, P Ponka, and D R Richardson. (2002). Erythroid differentiation and protoporphyrin IX down-regulate frataxin expression in Friend cells: characterization of frataxin expression compared to molecules involved in iron metabolism and hemoglobinization. Blood 99:3813–3822.
  • E P Whitlock, B A Garlitz, E L Harris, T L Beil, and P R Smith. (2006). Screening for hereditary hemochromatosis: a systematic review for the US Preventive Services Task Force. Ann Intern Med 145:209–223.
  • O T Ayonrinde, and J K Olynyk. (2007). Clinical expression of hemochromatosis gene (HFE) variants. Hepatology 46:960–962.
  • B A Leggett, J W Halliday, N N Brown, S Bryant, and L W Powell. (1990). Prevalence of haemochromatosis amongst asymptomatic Australians. Br J Haematol 74:525–530.
  • J Waalen, and E Beutler. (2005). Beware of multiple comparisons: a study of symptoms associated with mutations of the HFE hemochromatosis gene. Clin Chim Acta 361:128–134.
  • S M McDonnell, B L Preston, S A Jewell, J C Barton, C Q Edwards, P C Adams, and R Yip. (1999). A survey of 2,851 patients with hemochromatosis: symptoms and response to treatment. Am J Med 106:619–624.
  • A S Tavill. (2001). Diagnosis and management of hemochromatosis. Hepatology 33:1321–1328.
  • M B Delatycki, L W Powell, and K J Allen. (2004). Hereditary hemochromatosis genetic testing of at-risk children: what is the appropriate age?. Genet Test 8:98–103.
  • E Beutler, V J Felitti, J A Koziol, N J Ho, and T Gelbart. (2002). Penetrance of 845G—A (C282Y) HFE hereditary haemochromatosis mutation in the USA. Lancet 359:211–218.
  • A Asberg, K Hveem, K Thorstensen, E Ellekjaer, K Kannelonning, U Fjosne, T B Halvorsen, H BG Smethurst, E Sagen, and K S Bjerve. (2001). Screening for hemochromatosis: high prevalence and low morbidity in an unselected population of 65,238 persons. Scand J Gastroenterol 36:1108–1115.
  • C A McCune, L N Al-Jader, A May, S L Hayes, H A Jackson, and M Worwood. (2002). Hereditary haemochromatosis: only 1% of adult HFE C282Y homozygotes in South Wales have a clinical diagnosis of iron overload. Hum Genet 111:538–543.
  • K J Allen, L C Gurrin, C C Constantine, N J Osborne, M B Delatycki, A J Nicoll, C E McLaren, M Bahlo, A E Nisselle, C D Vulpe, G J Anderson, M C Southey, G G Giles, D R English, J L Hopper, J K Olynyk, L W Powell, and D M Gertig. (2008). Iron-overload-related disease in HFE hereditary hemochromatosis. N Engl J Med 358:221–230.
  • M L Bassett, J W Halliday, and L W Powell. (1986). Value of hepatic iron measurements in early hemochromatosis and determination of the critical iron level associated with fibrosis. Hepatology 6:24–29.
  • L M Fletcher, J L Dixon, D M Purdie, L W Powell, and D HG Crawford. (2002). Excess alcohol greatly increases the prevalence of cirrhosis in hereditary hemochromatosis. Gastroenterology 122:281–289.
  • E Rossi, M K Bulsara, J K Olynyk, D J Cullen, L Summerville, and L W Powell. (2001). Effect of hemochromatosis genotype and lifestyle factors on iron and red cell indices in a community population. Clin Chem 47:202–208.
  • C A McCune, D Ravine, K Carter, H A Jackson, D Hutton, J Hedderich, M Krawczak, and M Worwood. (2006). Iron loading and morbidity among relatives of HFE C282Y homozygotes identified either by population genetic testing or presenting as patients. Gut 55:554–562.
  • E A Milward, S K Baines, M W Knuiman, H C Bartholomew, M L Divitini, D G Ravine, D G Bruce, and J K Olynyk. (2008). Non-citrus fruits as novel dietary environmental modifiers of iron stores in people with or without HFE gene mutations. Mayo Clin Proc 83:543–549.
  • L W Powell, E Jazwinska, and J Halliday. (1994). Changing concepts of haemochromatosis. Adv Exp Med Biol 356:285–291.
  • N Milman. (1996). Serum ferritin in Danes: studies of iron status from infancy to old age, during blood donation and pregnancy. Int J Hematol 63:103–135.
  • G Willis, V Bardsley, I W Fellows, R Lonsdale, J Z Wimperis, and B A Jennings. (2005). Hepatocellular carcinoma and the penetrance of HFE C282Y mutations: a cross sectional study. BMC Gastroenterol 5:17.
  • C Niederau, R Fischer, A Purschel, W Stremmel, D Haussinger, and G Strohmeyer. (1996). Long-term survival in patients with hereditary hemochromatosis. Gastroenterology 110:1107–1119.
  • B R Bacon, J K Olynyk, E M Brunt, R S Britton, and R K Wolff. (1999). HFE genotype in patients with hemochromatosis and other liver diseases. Ann Intern Med 130:953–962.
  • D HG Crawford, L M Fletcher, S G Hubscher, K A Stuart, E Gane, P W Angus, G P Jeffrey, G W McCaughan, P Kerlin, L W Powell, and E E Elias. (2004). Patient and graft survival after liver transplantation for hereditary hemochromatosis: implications for pathogenesis. Hepatology 39:1655–1662.
  • P C Adams. (2001). Is there a threshold of hepatic iron concentration that leads to cirrhosis in C282Y hemochromatosis?. Am J Gastroenterol 96:567–569.
  • J S Axford. (1991). Rheumatic manifestations of haemochromatosis. Baillieres Clin Rheumatol 5:351–365.
  • R Faraawi, M Harth, A Kertesz, and D Bell. (1993). Arthritis in hemochromatosis. J Rheumatol 20:448–452.
  • J Olynyk, P Hall, M Ahern, R Kwiatek, and M Mackinnon. (1994). Screening for genetic haemochromatosis in a rheumatology clinic. Aust N Z J Med 24:22–25.
  • G Willis, D GI Scott, B A Jennings, K Smith, M Bukhari, and J Z Wimperis. (2002). HFE mutations in an inflammatory arthritis population. Rheumatology (Oxford) 41:176–179.
  • C A Sherrington, M W Knuiman, M L Divitini, H C Bartholomew, D J Cullen, and J K Olynyk. (2006). Population-based study of the relationship between mutations in the hemochromatosis (HFE) gene and arthritis. J Gastroenterol Hepatol 21:595–598.
  • Z J Bulaj, R S Ajioka, J D Phillips, B A LaSalle, L B Jorde, L M Griffen, C Q Edwards, and J P Kushner. (2000). Disease-related conditions in relatives of patients with hemochromatosis. N Engl J Med 343:1529–1535.
  • J T Salonen, K Nyyssonen, H Korpela, J Tuomilehto, R Seppanen, and R Salonen. (1992). High stored iron levels are associated with excess risk of myocardial-infarction in eastern Finnish men. Circulation 86:803–811.
  • T P Tuomainen, K Kontula, K Nyyssonen, T A Lakka, T Helio, and J T Salonen. (1999). Increased risk of acute myocardial infarction in carriers of the hemochromatosis gene Cys282Tyr mutation—A prospective cohort study in men in eastern Finland. Circulation 100:1274–1279.
  • M Miller, and G M Hutchins. (1994). Hemochromatosis, multiorgan hemosiderosis, and coronary-artery disease. JAMA 272:231–233.
  • R F Franco, M A Zago, M D Trip, H ten Cate, A van den Ende, M H Prins, J JP Kastelein, and P H Reitsma. (1998). Prevalence of hereditary haemochromatosis in premature atherosclerotic vascular disease. Br J Haematol 102:1172–1175.
  • C J Fox, D J Cullen, M W Knuiman, G N Cumpston, M L Divitini, E Rossi, P A Gochee, L W Powell, and J K Olynyk. (2002). Effects of body iron stores and haemochromatosis genotypes on coronary heart disease outcomes in the Busselton health study. J Cardiovasc Risk 9:287–293.
  • I Porto, A M Leone, F Crea, and F Andreotti. (2005). Inflammation, genetics, and ischemic heart disease: focus on the major histocompatibility complex (MHC) genes. Cytokine 29:187–196.
  • A D van der, J J Marx, D E Grobbee, M H Kamphuis, N A Georgiou, J H van Kats-Renaud, W Breuer, Z I Cabantchik, M Roest, H A Voorbij, and Y T van der Schouw. (2006). Non-transferrin-bound iron and risk of coronary heart disease in postmenopausal women. Circulation 113:1942–1949.
  • C Mandelli, L Cesarini, A Piperno, S Fargion, A L Fracanzani, D Barisani, and D Conte. (1992). Saturability of hepatic iron deposits in genetic hemochromatosis. Hepatology 16:956–959.
  • P C Adams, Y Deugnier, R Moirand, and P Brissot. (1997). The relationship between iron overload, clinical symptoms, and age in 410 patients with genetic hemochromatosis. Hepatology 25:162–166.
  • Q Yang, S M McDonnell, M J Khoury, J Cono, and R G Parrish. (1998). Hemochromatosis-associated mortality in the United States from 1979 to 1992: an analysis of multiple-cause mortality data. Ann Intern Med 129:946–953.
  • L M Ptaszek, E T Price, M Y Hu, and P C Yang. (2005). Early diagnosis of hemochromatosis-related cardiomyopathy with magnetic resonance imaging. J Cardiovasc Magn Reson 7:689–692.
  • A Pepe, V Positano, M F Santarelli, F Sorrentino, E Cracolici, D De Marchi, A Maggio, M Midiri, L Landini, and M Lombardi. (2006). Multislice multiecho T2cardiovascular magnetic resonance for detection of the heterogeneous distribution of myocardial iron overload. J Magn Reson Imaging 23:662–668.
  • U Sechtem, H Mahrholdt, and H Vogelsberg. (2007). Cardiac magnetic resonance in myocardial disease. Heart 93:1520–1527.
  • S DuBois, and K V Kowdley. (2004). Review article. Targeted screening for hereditary haemochromatosis in high-risk groups. Aliment Pharmacol Ther 20:1–14.
  • A Dabestani, J S Child, J K Perloff, W G Figueroa, H R Schelbert, and T R Engel. (1988). Cardiac abnormalities in primary hemochromatosis. Ann NY Acad Sci 526:234–244.
  • A Holstein, S Hinze, E Thiessen, A Plaschke, and E H Egberts. (2002). Clinical implications of hepatogenous diabetes in liver cirrhosis. J Gastroenterol Hepatol 17:677–681.
  • E S Albright, and D SH Bell. (2003). The liver, liver disease and diabetes mellitus. Endocrinologist 13:58–66.
  • D Conte, D Manachino, A Colli, A Guala, G Aimo, M Andreoletti, M Corsetti, and M Fraquelli. (1998). Prevalence of genetic hemochromatosis in a cohort of Italian patients with diabetes mellitus. Ann Intern Med 128:370–373.
  • C Ellervik, T Mandrup-Poulsen, B G Nordestgaard, L E Larsen, M Appleyard, M Frandsen, P Petersen, P Schlichting, T Saermark, A Tybjaerg-Hansen, and H Birgens. (2001). Prevalence of hereditary haemochromatosis in late-onset type 1 diabetes mellitus: a retrospective study. Lancet 358:1405–1409.
  • D A McClain, D Abraham, J Rogers, R Brady, P Gault, R Ajioka, and J P Kushner. (2006). High prevalence of abnormal glucose homeostasis secondary to decreased insulin secretion in individuals with hereditary haemochromatosis. Diabetologia 49:1661–1669.
  • R V Andersen, A Tybjaerg-Hansen, M Appleyard, H Birgens, and B G Nordestgaard. (2004). Hemochromatosis mutations in the general population: iron overload progression rate. Blood 103:2914–2919.
  • J Waalen, B G Nordestgaard, and E Beutler. (2005). The penetrance of hereditary hemochromatosis. Best Pract Res Clin Haematol 18:203–220.
  • R T Acton, D M Reboussin, J C Barton, G D McLaren, L V Passmore, E L Harris, P C Adams, T C Bent, M R Speechley, T M Vogt, O Castro, and P Sholinsky. (2006). Relationships of serum ferritin, transferrin saturation, and HFE mutations and self-reported diabetes in the hemochromatosis and iron overload screening (HEIRS) study. Diabetes Care 29:2084–2089.
  • C Ellervik, H Birgens, A Tybjaerg-Hansen, and B G Nordestgaard. (2007). Hemochromatosis genotypes and risk of 31 disease endpoints: meta-analyses including 66,000 cases and 226,000 controls. Hepatology 46:1071–1080.
  • D J Halsall, I McFarlane, J Luan, T M Cox, and N J Wareham. (2003). Typical type 2 diabetes mellitus and HFE gene mutations: a population-based case-control study. Hum Mol Genet 12:1361–1365.
  • D Dubois-Laforgue, E Larger, and J Timsit. (2000). Is diabetes mellitus a sufficient condition to suspect hemochromatosis?. Diabetes Metab 26:318–321.
  • M J Sampson, T Williams, P J Heyburn, R H Greenwood, R C Temple, J Z Wimperis, B A Jennings, and G A Willis. (2000). Prevalence of HFE (hemochromatosis gene) mutations in unselected male patients with type 2 diabetes. J Lab Clin Med 135:170–173.
  • M B Youdim, and S Yehuda. (2000). The neurochemical basis of cognitive deficits induced by brain iron deficiency: involvement of dopamine-opiate system. Cell Mol Biol (Noisy-le-grand) 46:491–500.
  • Y Ke, and Z M Qian. (2003). Iron misregulation in the brain: a primary cause of neurodegenerative disorders. Lancet Neurol 2:246–253.
  • L Zecca, M BH Youdim, P Riederer, J R Connor, and R R Crichton. (2004). Iron, brain ageing and neurodegenerative disorders. Nat Rev Neurosci 5:863–873.
  • D J Pinero, J Hu, and J R Connor. (2000). Alterations in the interaction between Fe regulatory proteins and their Fe responsive element in normal and Alzheimer's diseased brains. Cell Mol Biol (Noisy-le-grand) 46:761–776.
  • J R Connor, E A Milward, S Moalem, M Percy, M Sampietro, C Vergani, R J Scott, and M Chorney. (2001). Is hemochromatosis a risk factor for Alzheimer's disease?. J Alzheimers Dis 3:471–477.
  • K Senior. (2001). New genes reveal major role for iron in neurodegeneration. Lancet 358:302.
  • A R Curtis, C Fey, C M Morris, L A Bindoff, P G Ince, P F Chinnery, A Coulthard, M J Jackson, A P Jackson, D P McHale, D Hay, W A Barker, A F Markham, D Bates, A Curtis, and J Burn. (2001). Mutation in the gene encoding ferritin light polypeptide causes dominant adult-onset basal ganglia disease. Nat Genet 28:350–354.
  • D E Crompton, P F Chinnery, C Fey, A RJ Curtis, C M Morris, J Kierstan, A Burt, F Young, A Coulthard, A Curtis, P G Ince, D Bates, M J Jackson, and J Burn. (2002). Neuroferritinopathy: a window on the role of iron in neurodegeneration. Blood Cells Mol Dis 29:522–531.
  • X Xu, S Pin, M Gathinji, R Fuchs, and Z L Harris. (2004). Aceruloplasminemia. An inherited neurodegenerative disease with impairment of iron homeostasis. Ann NY Acad Sci 1012:299–305.
  • B Zhou, S K Westaway, B Levinson, M A Johnson, J Gitschier, and S J Hayflick. (2001). A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome. Nat Genet 28:345–349.
  • R Bhidayasiri, S L Perlman, S M Pulst, and D H Geschwind. (2005). Late-onset Friedreich ataxia: phenotypic analysis, magnetic resonance imaging findings, and review of the literature. Arch Neurol 62:1865–1869.
  • D Berg, U Hoggenmuller, E Hofmann, R Fischer, M Kraus, M Scheurlen, and G Becker. (2000). The basal ganglia in haemochromatosis. Neuroradiology 42:9–13.
  • T Moos, and E H Morgan. (2000). Transferrin and receptor function in brain barrier systems. Cell Mol Neurobiol 20:77–95.
  • T Moos, and E H Morgan. (2002). A morphological study of the developmentally regulated transport of iron into the brain. Dev Neurosci 24:99–105.
  • R Deane, W Zheng, and B V Zlokovic. (2004). Brain capillary endothelium and choroid plexus epithelium regulate transport of transferrin-bound and free iron into the rat brain. J Neurochem 88:813–820.
  • J M Bastin, M Jones, C A O'Callaghan, L Schimanski, D Y Mason, and A R Townsend. (1998). Kupffer cell staining by an HFE-specific monoclonal antibody: implications for hereditary haemochromatosis. Br J Haematol 103:931–941.
  • M A Smith, P L Harris, L M Sayre, and G Perry. (1997). Iron accumulation in Alzheimer disease is a source of redox-generated free radicals. Proc Natl Acad Sci USA 94:9866–9868.
  • G Bartzokis, D Sultzer, J Cummings, L E Holt, D B Hance, V W Henderson, and J Mintz. (2000). In vivo evaluation of brain iron in Alzheimer disease using magnetic resonance imaging. Arch Gen Psychiatry 57:47–53.
  • D Blacker, L Bertram, A J Saunder, T J Moscarillo, M S Albert, H Weiner, R T Perry, J S Collins, L E Harrell, R C Go, A J Mahoney, T M. D. F Beaty, D Avramopoulos, G A Chase, M F Folstein, M G McInnis, S S Bassett, K J Doheny, E W Pugh, and R E Tanzi. (2003). Results of a high resolution genome screen of 437 Alzheimer's disease families. Hum Mol Genet 12:1723–1732.
  • J F Pulliam, C D Jennings, R J Kryscio, D G Davis, D Wilson, T J Montine, F A Schmitt, and W R Markesbery. (2003). Association of HFE mutations with neurodegeneration and oxidative stress in Alzheimer's disease and correlation with APOE. Am J Med Genet B Neuropsychiatr Genet 119:48–53.
  • S Moalem, M E Percy, D F Andrews, T P Kruck, S Wong, A J Dalton, P Mehta, B Fedor, and A C Warren. (2000). Are hereditary hemochromatosis mutations involved in Alzheimer disease?. Am J Med Genet 93:58–66.
  • M Sampietro, L Caputo, A Casatta, M Meregalli, A Pellagatti, J Tagliabue, G Annoni, and C Vergani. (2001). The hemochromatosis gene affects the age of onset of sporadic Alzheimer's disease. Neurobiol Aging 22:563–568.
  • A Lleó, R Blesa, C Angelopoulos, P Pastor-Rubio, M Villa, R Oliva, and E Bufill. (2002). Transferrin C2 allele, haemochromatosis gene mutations, and risk for Alzheimer's disease. J Neurol Neurosurg Psychiatry 72:820–821.
  • D Berlin, G Chong, H Chertkow, H Bergman, N A Phillips, and H M Schipper. (2004). Evaluation of HFE (hemochromatosis) mutations as genetic modifiers in sporadic AD and MCI. Neurobiol Aging 25:465–474.
  • R J Guerreiro, J M Bras, I Santana, C Januario, B Santiago, A S Morgadinho, M H Ribeiro, J Hardy, A Singleton, and C Oliveira. (2006). Association of HFE common mutations with Parkinson's disease, Alzheimer's disease and mild cognitive impairment in a Portuguese cohort. BMC Neurol 6:24–31.
  • M S Golub, S L Germann, R S Araiza, J R Reader, S M Griffey, and K CK Lloyd. (2005). Movement disorders in the Hfe knockout mouse. Nutr Neurosci 8:239–244.
  • d i Martinez, F Montemuros, D Tavazzi, E Salsano, T Piepoli, B Pollo, G Fiorelli, and G Finocchiaro. (2001). High frequency of the H63D mutation of the hemochromatosis gene (HFE) in malignant gliomas. Neurology 57:1342.
  • C Chapman, L Johnson, M Marriott, G Mraz, B Tait, C Wilkinson, B Taylor, T P Speed, S J Foote, and T J Kilpatrick. (2004). Extended haplotype analysis in the HLA complex reveals an increased frequency of the HFE-C282Y mutation in individuals with multiple sclerosis. Hum Genet 114:573–580.
  • J Haba-Rubio, L Staner, C Petiau, G Erb, T Schunck, and J P Macher. (2005). Restless legs syndrome and low brain iron levels in patients with haemochromatosis. J Neurol Neurosurg Psychiatry 76:1009–1010.
  • L J Stovner, K Hagen, A Waage, and K S Bjerve. (2002). Hereditary haemochromatosis in two cousins with cluster headache. Cephalgia 22:317–319.
  • A A Yen, E P Simpson, J S Henkel, D R Beers, and S H Appel. (2004). HFE mutations are not strongly associated with sporadic ALS. Neurology 62:1611–1612.
  • L E Beckman, G F Van Landeghem, C Sikstrom, A Wahlin, B Markevarn, G Hallmans, P Lenner, L Athlin, R Stenling, and L Beckman. (1999). Interaction between haemochromatosis and transferrin receptor genes in different neoplastic disorders. Carcinogenesis 20:1231–1233.
  • J Fuchs, M Podda, L Packer, and R Kaufmann. (2002). Morbidity risk in HFE associated hereditary hemochromatosis C282Y heterozygotes. Toxicology 180:169–181.
  • A R Kallianpur, L D Hall, M Yadav, B W Christman, R S Dittus, J L Haines, F F Parl, and M L Summar. (2004). Increased prevalence of the HFE C282Y hemochromatosis allele in women with breast cancer. Cancer Epidemiol Biomarkers Prev 13:205–212.
  • B K Abraham, C Justenhoven, B Pesch, V Harth, G Weirich, C Baisch, S Rabstein, Y D Ko, T Bruning, H P Fischer, S Haas, S Brod, C Oberkanins, U Hamann, and H Brauch. (2005). Investigation of genetic variants of genes of the hemochromatosis pathway and their role in breast cancer. Cancer Epidemiol Biomarkers Prev 14:1102–1107.
  • K A McGlynn, L C Sakoda, Y Hu, R E Schoen, R S Bresalier, M Yeager, S Chanock, R B Hayes, and K H Buetow. (2005). Hemochromatosis gene mutations and distal adenomatous colorectal polyps. Cancer Epidemiol Biomarkers Prev 14:158–163.
  • N J Osborne, L C Gurrin, K J Allen, C C Constantine, M B Delatycki, A E Nisselle, A R Fletcher, C E McLaren, D R English, J L Hopper, G G Giles, J Olynyk, A Nicoll, L W Powell, and D M Gertig. (2007). Homozygosity for the C282Y mutation in the HFE gene is associated with increased risk of colorectal and breast cancer in Australian population. Am J Hematol 82:575.
  • M T Dorak, A K Burnett, and M Worwood. (2005). HFE gene mutations in leukemia: HuGE review susceptibility to childhood. Genet Med 7:159–168.
  • E Rossi, D F Wallace, V N Subramaniam, T G St Pierre, C Mews, and G P Jeffrey. (2006). Clinical expression of C282Y homozygous HFE hemochromatosis at 14 years of age. Ann Clin Biochem 43:233–236.
  • M O Van Aken, A J De Craen, J Gussekloo, P H Moghaddam, J P Vandenbroucke, B T Heijmans, P E Slagboom, and R G Westendorp. (2002). No increase in mortality and morbidity among carriers of the C282Y mutation of the hereditary haemochromatosis gene in the oldest old: the Leiden 85-plus study. Eur J Clin Invest 32:750–754.
  • G Willis, J Z Wimperis, K Smith, I W Fellows, and B A Jennings. (2003). HFE mutations in the elderly. Blood Cells Mol Dis 31:240–246.
  • E Rossi, J K Olynyk, D J Cullen, G Papadopoulos, M Bulsara, L Summerville, and L W Powell. (2000). Compound heterozygous hemochromatosis genotype predicts increased iron and erythrocyte indices in women. Clin Chem 46:162–166.
  • A Geier, C Gartung, I Theurl, G Weiss, F Lammert, C G Dietrich, R Weiskirchen, H Zoller, B Hermanns, and S Matern. (2005). Occult celiac disease prevents penetrance of hemochromatosis. World J Gastroenterol 11:3323–3326.
  • C E McLaren, G J McLachlan, J W Halliday, S I Webb, B A Leggett, E C Jazwinska, D H Crawford, V R Gordeuk, G D McLaren, and L W Powell. (1998). Distribution of transferrin saturation in an Australian population: relevance to the early diagnosis of hemochromatosis. Gastroenterology 114:543–549.
  • B R Bacon. (2001). Hemochromatosis: diagnosis and management. Gastroenterology 120:718–725.
  • J Waalen, V J Felitti, T Gelbart, and E Beutler. (2008). Screening for hemochromatosis by measuring ferritin levels: a more effective approach. Blood 111:3373–3376.
  • J K Olynyk, S E Hagan, D J Cullen, J Beilby, and D E Wihttall. (2004). Evolution of untreated hereditary hemochromatosis in the Busselton population: a 17-year study. Mayo Clin Proc 79:309–313.
  • P C Adams, D M Reboussin, C Leiendecker-Foster, G C Moses, G D McLaren, C E McLaren, F W Dawkins, I Kasvosve, R T Acton, J C Barton, D Zaccaro, E L Harris, R Press, H Chang, and J H Eckfeldt. (2005). Comparison of the unsaturated iron-binding capacity with transferrin saturation as a screening test to detect C282Y homozygotes for hemochromatosis in 101,168 participants in the hemochromatosis and iron overload screening (HEIRS) study. Clin Chem 51:1048–1052.
  • D Vartsky, K J Ellis, D M Hull, and S H Cohn. (1979). Nuclear resonant scattering of gamma rays—A new technique for in vivo measurement of body iron stores. Phys Med Biol 24:689–701.
  • A W Leung, R E Steiner, and I R Young. (1984). Nmr imaging of the liver in 2 cases of iron overload. J Comput Assist Tomogr 8:446–449.
  • G M Brittenham, and D G Badman. (2003). Noninvasive measurement of iron: report of an NIDDK workshop. Blood 101:15–19.
  • J M Alustiza, J Artetxe, A Castiella, C Agirre, J I Emparanza, P Otazua, M Garcia-Bengoechea, J Barrio, F Mujica, and J A Recondo. (2004). MR quantification of hepatic iron concentration. Radiology 230:479–484.
  • T G St Pierre, P R Clark, W Chua-anusorn, A J Fleming, G P Jeffrey, J K Olynyk, P Pootrakul, E Robins, and R Lindeman. (2005). Noninvasive measurement and imaging of liver iron concentrations using proton magnetic resonance. Blood 105:855–861.
  • Y Gandon, D Olivie, D Guyader, C Aube, F Oberti, V Sebille, and Y Deugnier. (2004). Non-invasive assessment of hepatic iron stores by MRI. Lancet 363:357–362.
  • D Guyader, C Jacquelinet, R Moirand, B Turlin, M H Mendler, J Chaperon, V David, P Brissot, P Adams, and Y Deugnier. (1998). Noninvasive prediction of fibrosis in C282Y homozygous hemochromatosis. Gastroenterology 115:929–936.
  • E M Brunt, J K Olynyk, R S Britton, C G Janney, A M Di Bisceglie, and B R Bacon. (2000). Histological evaluation of iron in liver biopsies: relationship to HFE mutations. Am J Gastroenterol 95:1788–1793.
  • G Kent, and H Popper. (1968). Liver biopsy in diagnosis of hemochromatosis. Am J Med 44:837–841.
  • E W Clayton. (2003). Ethical, legal, and social implications of genomic medicine. N Engl J Med 349:562–569.
  • K Pollitz, B N Peshkin, E Bangit, and K Lucia. (2007). Genetic discrimination in health insurance: current legal protections and industry practices. Inquiry 44:350–368.
  • W Burke, E Thomson, M J Khoury, S M McDonnell, N Press, P C Adams, J C Barton, E Beutler, G Brittenham, A Buchanan, E W Clayton, M E Cogswell, E M Meslin, A G Motulsky, L W Powell, E Sigal, B S Wilfond, and F S Collins. (1998). Hereditary hemochromatosis—Gene discovery and its implications for population-based screening. JAMA 280:172–178.
  • J S Alper, L N Geller, C I Barash, P R Billings, V Laden, and M R Natowicz. (1994). Genetic discrimination and screening for hemochromatosis. J Public Health Policy 15:345–358.
  • M Delatycki, K Allen, and R Williamson. (2002). Insurance agreement to facilitate genetic testing. Lancet 359:1433.
  • M B Delatycki, K J Allen, A E Nisselle, V Collins, S Metcalfe, D du Sart, J Halliday, M A Aitken, I Macciocca, V Hill, A Wakefield, A Ritchie, A A Gason, A J Nicoll, L W Powell, and R Williamson. (2005). Use of community genetic screening to prevent HFE-associated hereditary haemochromatosis. Lancet 366:314–316.
  • T E Power, and P C Adams. (2001). Psychosocial impact of C282Y mutation testing for hemochromatosis. Genet Test 5:107–110.
  • J P Kaltwasser, E Werner, K Schalk, C Hansen, R Gottschalk, and C Seidl. (1998). Clinical trial on the effect of regular tea drinking on iron accumulation in genetic haemochromatosis. Gut 43:699–704.
  • L Yu, and G N Ioannou. (2007). Survival of liver transplant recipients with hemochromatosis in the United States. Gastroenterology 133:489–495.
  • H R Schumacher, P C Straka, M A Krikker, and A T Dudley. (1988). The arthropathy of hemochromatosis—recent Studies. Ann NY Acad Sci 526:224–233.

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