Disorders of iron metabolism

New England Journal of Medicine

Volumn 341, Issue 26, 1999, Pages 1986-1995

  Andrews, Nancy C ^a,b  

^a HOWARD HUGHES MEDICAL INSTITUTE   (United States)

^b BOSTON CHILDREN S HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DEFEROXAMINE; FERRITIN; IRON; IRON CHELATING AGENT;

HEMOCHROMATOSIS; HUMAN; IRON ABSORPTION; IRON DEFICIENCY; IRON DEFICIENCY ANEMIA; IRON METABOLISM; IRON OVERLOAD; IRON THERAPY; IRON TRANSPORT; PHLEBOTOMY; PRIORITY JOURNAL; REVIEW; SIDEROSIS;

BIOLOGICAL TRANSPORT, ACTIVE; HUMANS; INTESTINAL ABSORPTION; IRON; IRON METABOLISM DISORDERS;

EID: 0033599057     PISSN: 00284793     EISSN: None     Source Type: Journal    
DOI: 10.1056/NEJM199912233412607     Document Type: Review

References (86)

1. Bothwell TH, Finch CA. Iron metabolism. Boston: Little, Brown, 1962.
2. Aisen P, Wessling-Resnick M, Leibold EA. Iron metabolism. Curr Opin Chem Biol 1999;3:200-6.
3. Fleming MD, Romano MA, Su MA, Garrick LM, Garrick MD, Andrews NC. Nramp2 is mutated in the anemic Belgrade (b) rat: evidence of a role for Nramp2 in endosomal iron transport. Proc Natl Acad Sci U S A 1998;95:1148-53.
4. Andrews NC, Bridges KR. Disorders of iron metabolism and sideroblastic anemia. In: Nathan DG, Orkin SH, eds. Nathan and Oski's hematology of infancy and childhood. 5th ed. Vol. 1. Philadelphia: W.B. Saunders, 1998:423-61.
5. Cook JD, Barry WE, Hershko C, Fillet G, Finch CA. Iron kinetics with emphasis on iron overload. Am J Pathol 1973;72:337-43.
6. Riedel H-D, Remus AJ, Fitscher BA, Stremmel W. Characterization and partial purification of a ferrireductase from human duodenal microvillus membranes. Biochem J 1995;309:745-8.
7. Fleming MD, Trenor CC III, Su MA, et al. Microcytic anaemia mice have a mutation in Nramp2, a candidate iron transporter gene. Nat Genet 1997;16:383-6.
8. Gunshin H, Mackenzie B, Berger UV, et al. Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 1997; 388:482-8.
9. McKie AT, Wehr K, Simpson RJ, Peters TJ, Hentze MW, Farzaneh F. Molecular cloning and characterisation of a novel duodenal-specific gene implicated in iron absorption. Biochem Soc Trans 1998;26:S264.
10. Vulpe CD, Kuo YM, Murphy TL, et al. Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. Nat Genet 1999;21:195-9.
11. Hahn PF, Bale WF, Ross JF, Balfour WM, Whipple GH. Radioactive iron absorption by the gastro-intestinal tract: influence of anemia, anoxia, and antecedent feeding distribution in growing dogs. J Exp Med 1943;78:169-88.
12. Finch C. Regulators of iron balance in humans. Blood 1994;84:1697-702.
13. Guggenheim KY. Chlorosis: the rise and disappearance of a nutritional disease. J Nutr 1995;125:1822-5.
14. Looker AC, Dallman PR, Carroll MD, Gunter EW, Johnson CL. Prevalence of iron deficiency in the United States. JAMA 1997;277:973-6.
15. Brugnara C, Zurakowski D, DiCanzio J, Boyd T, Platt O. Reticulocyte hemoglobin content to diagnose iron deficiency in children. JAMA 1999; 281:2225-30.
16. Pollitt E. Iron deficiency and cognitive function. Annu Rev Nutr 1993;13:521-37.
17. Moore DF Jr, Sears DA. Pica, iron deficiency, and the medical history. Am J Med 1994;97:390-3.
18. Heilmeyer L, Keller W, Vivell O, et al. Congenital transferrin deficiency in a seven-year old girl. German Med Mon 1961;6:385-9.
19. Goya N, Miyazaki S, Kodate S, Ushio B. A family of congenital atransferrinemia. Blood 1972;40:239-45.
20. Hamill RL, Woods JC, Cook BA. Congenital atransferrinemia: a case report and review of the literature. Am J Clin Pathol 1991;96:215-8.
21. Hayashi A, Wada Y, Suzuki T, Shimizu A. Studies on familial hypotransferrinemia: unique clinical course and molecular pathology. Am J Hum Genet 1993;53:201-13.
22. Buchanan GR, Sheehan RG. Malabsorption and defective utilization of iron in three siblings. J Pediatr 1981;98:723-8.
23. Hartman KR, Barker JA. Microcytic anemia with iron malabsorption: an inherited disorder of iron metabolism. Am J Hematol 1996;51:269-75.
24. Bannerman RM. Of mice and men and microcytes. J Pediatr 1981;98: 760-2.
25. Galanello R, Cau M, Melis MA, Deidda F, Cao A, Cazzola M. Studies of NRAMP2, transferrin receptor and transferrin genes as candidate genes for human hereditary microcytic anemia due to defective iron absorption and utilization. Blood 1998;92:Suppl 1:669a. abstract.
26. Blaud P. Sur les maladies chlorotiques et sur un mode de traitement specifique dans ces affections. Rev Med Fr Etrang 1832;45:357-67.
27. Oski FA, Naiman JL, eds. Hematologic problems in the newborn. 3rd ed. Vol. 4 of Major problems in clinical pediatrics. Philadelphia: W.B. Saunders, 1982:32-3.
28. American Academy of Pediatrics, Committee on Nutrition. Iron fortification of infant formulas. Pediatrics 1999;104:119-23.
29. Auerbach M, Witt D, Toler W, Fierstein M, Lerner RG, Ballard H. Clinical use of the total dose intravenous infusion of iron dextran. J Lab Clin Med 1988;111:566-70.
30. Ferguson BJ, Skikne BS, Simpson KM, Baynes RD, Cook JD. Serum transferrin receptor distinguishes the anemia of chronic disease from iron deficiency anemia. J Lab Clin Med 1992;119:385-90.
31. Jurado RL. Iron, infections, and anemia of inflammation. Clin Infect Dis 1997;25:888-95.
32. Trousseau A. Glycosurie: diabete sucre. Clin Med Hotel Dieu Paris 1865;2:663-98.
33. von Recklinghausen FD. Uber haemochromatose. Tageblatt Versammlung Dtsch Naturforsch Artze Herdelbert 1889;62:324-5.
34. Simon M, Bourel M, Fauchet R, Genetet B. Association of HLA-A3 and HLA-B14 antigens with idiopathic haemochromatosis. Gut 1976;17: 332-4.
35. Feder JN, Gnirke A, Thomas W, et al. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 1996; 13:399-408.
36. Ajioka RS, Jorde LB, Gruen JR, et al. Haplotype analysis of hemochromatosis: evaluation of different linkage-disequilibrium approaches and evolution of disease chromosomes. Am J Hum Genet 1997;60:1439-47.
37. Edwards CQ, Griffen LM, Goldgar D, Drummond C, Skolnick MH, Kushner JP. Prevalence of hemochromatosis among 11,065 presumably healthy blood donors. N Engl J Med 1988;318:1355-62.
38. Barton JC, Sawada-Hirai R, Rothenberg BE, Acton RT. Two novel missense mutations of the HFE gene (I105T and G93R) and identification of the S65C mutation in Alabama hemochromatosis probands. Blood Cells Mol Dis 1999;25:147-55.
39. Mura C, Raguenes O, Ferec C. HFE mutations analysis in 711 hemochromatosis probands: evidence for S65C implication in mild form of hemochromatosis. Blood 1999;93:2502-5.
40. Wallace DF, Dooley JS, Walker AP. A novel mutation of HFE explains the classical phenotype of genetic hemochromatosis in a C282Y heterozygote. Gastroenterology 1999;116:1409-12.
41. Bacon BR, Olynyk JK, Brunt EM, Britton RS, Wolff RK. HFE genotype in patients with hcmochromatosis and other liver diseases. Ann Intern Med 1999;130:953-62.
42. Olynyk JK, Cullen DJ, Aquilia S, Rossi E, Summerville L, Powell LW. A population-based study of the clinical expression of the hemochromatosis gene. N Engl J Med 1999;341:718-24.
43. Lebron JA, Bennett MJ, Vaughn DE, et al. Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor. Cell 1998;93:111-23.
44. Parkkila S, Waheed A, Britton RS, et al. Association of the transferrin receptor in human placenta with HFE, the protein defective in hereditary hemochromatosis. Proc Natl Acad Sci U S A 1997;94:13198-202.
45. Feder JN, Penny DM, Irrinki A, et al. The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding. Proc Natl Acad Sci USA 1998;95:1472-7.
46. Eisenstein RS. Interaction of the hemochromatosis gene product HFE with transferrin receptor modulates cellular iron metabolism. Nutr Rev 1998;56:356-8.
47. Waheed A, Parkkila S, Saarnio J, et al. Association of HFE protein with transferrin receptor in crypt enterocytes of human duodenum. Proc Natl Acad Sci U S A 1999;96:1579-84.
48. Roy CN, Penny DM, Feder JN, Enns CA. The hereditary hemochromatosis protein, HFE, specifically regulates transferrin-mediated iron uptake in HcLa cells. J Biol Chem 1999;274:9022-8.
49. Zhou XY, Tomatsu S, Fleming RE, et al. HFE gene knockout produces mouse model of hereditary hemochromatosis. Proc Natl Acad Sci U S A 1998;95:2492-7.
50. Levy JE, Montross LK, Cohen DE, Fleming MD, Andrews NC. The C282Y mutation causing hereditary hemochromatosis does not produce a null allele. Blood 1999;94:9-11.
51. Pietrangelo A, Montosi G, Totaro A, et al. Hereditary hemochromatosis in adults without pathogenic mutations in the hemochromatosis gene. N Engl J Med 1999;341:725-32.
52. Davis WD Jr, Arrowsmith WR. The effect of repeated bleeding in hemochromatosis. J Lab Clin Med 1950;36:814-5. abstract.
53. Barton JC, McDonnell SM, Adams PC, et al. Management of hemochromatosis. Ann Intern Med 1998;129:932-9.
54. Gordeuk VR. Hereditary and nutritional iron overload. Baillieres Clin Haematol 1992;5:169-86.
55. Gordeuk V, Mukiibi J, Hasstedt SJ, et al. Iron overload in Africa: interaction between a gene and dietary iron content. N Engl J Med 1992; 326:95-100.
56. Moyo VM, Mandishona E, Hasstedt SJ, et al. Evidence of genetic transmission in African iron overload. Blood 1998;91:1076-82.
57. McNamara L, MacPhail AP, Gordeuk VR, Hasstedt SJ, Rouault T. Is there a link between African iron overload and the described mutations of the hereditary hemochromatosis gene? Br J Haematol 1998;102:1176-8.
58. Gangaidzo IT, Moyo VM, Saungweme T, et al. Iron overload in urban Africans in the 1990s. Gut 1999;45:278-83.
59. Gordeuk VR, McLaren CE, MacPhail AP, Deichsel G, Bothwell TH. Associations of iron overload in Africa with hepatocellular carcinoma and tuberculosis: Strachan's 1929 thesis revisited. Blood 1996;87:3470-6.
60. Moyo VM, Gangaidzo IT, Gordeuk VR, Kiire CF, Macphail AP. Tuberculosis and iron overload in Africa: a review. Cent Afr J Med 1997;43:334-9.
61. Barton IC, Edwards CQ, Bertoli LF, Shroyer TW, Hudson SL. Iron overload in African Americans. Am J Med 1995;99:616-23.
62. Wurapa RK, Gordeuk VR, Brittenham GM, Khiyami A, Schechter GP, Edwards CQ. Primary iron overload in African Americans. Am J Med 1996;101:9-18.
63. Baer D. Hereditary iron overload and African Americans. Am J Med 1996;101:5-8.
64. Monaghan KG, Rybicki BA, Shurafa M, Feldman GL. Mutation analysis of the HFE gene associated with hereditary hemochromatosis in African Americans. Am J Hematol 1998;58:213-7.
65. Gordeuk VR, McLaren CE, Looker AC, Hasselblad V, Brittenham GM. Distribution of transferrin saturations in the African-American population. Blood 1998;91:2175-9.
66. Camaschella C, Roetto A, Cicilano M, et al. Juvenile and adult hemochromatosis are distinct genetic disorders. Eur J Hum Genet 1997;5: 371-5.
67. Camaschella C, Fargion S, Sampietro M, et al. Inherited HFE-unrelated hemochromatosis in Italian families. Hepatology 1999;29:1563-4.
68. Roetto A, Totaro A, Cazzola M, et al. Juvenile hemochromatosis locus maps to chromosome Iq. Am J Hum Genet 1999;64:1388-93.
69. Knisely AS. Neonatal hemochromatosis. Adv Pediatr 1992;39:383-403.
70. Goldfischer S, Grotsky HW, Chang CH, et al. Idiopathic neonatal iron storage involving the liver, pancreas, heart, and endocrine and exocrine glands. Hepatology 1981;1:58-64.
71. Blisard KS, Bartow SA. Neonatal hemochromatosis. Hum Pathol 1986;17:376-83.
72. Witzleben CL, Uri A. Perinatal hemochromatosis: entity or end result? Hum Pathol 1989;20:335-40.
73. Hoogstraten J, de Sa DJ, Knisely AS. Fetal liver disease may precede extrahepatic siderosis in neonatal hemochromatosis. Gastroenterology 1990;98:1699-701.
74. Danks D, Bodian M. A genetic study of neonatal obstructive jaundice. Arch Dis Child 1963;38:378-90.
75. Driscoll SG, Hayes AM, Levy HL. Neonatal hemochromatosis: evidence for autosomal recessive transmission. Am J Hum Genet 1988;43: Suppl:A232. abstract.
76. Dalhoj J, Kiaer H, Wiggers P, Grady RW, Jones RL, Knisely AS. Iron storage disease in parents and sibs of infants with neonatal hemochromatosis: 30-year follow-up. Am J Med Genet 1990;37:342-5.
77. Rand EB, McClenathan DT, Whitington PF. Neonatal hemochromatosis: report of successful orthotopic liver transplantation. J Pediatr Gastroenterol Nutr 1992;15:325-9.
78. Lund DP, Lillehei CW, Kevy S, et al. Liver transplantation in newborn liver failure: treatment for neonatal hemochromatosis. Transplant Proc 1993;25:1068-71.
79. Sigurdsson L, Reyes J, Kocoshis SA, Hansen TW, Rosh J, Knisely AS. Neonatal hemochromatosis: outcomes of pharmacologic and surgical therapies. J Pediatr Gastroenterol Nutr 1998;26:85-9.
80. Yoshida K, Furihata K, Takeda S, et al. A mutation in the ceruloplasmin gene is associated with systemic hemosiderosis in humans. Nat Genet 1995;9:267-72.
81. Harris ZL, Takahashi Y, Miyajima H, Serizawa M, MacGillivray RTA, Gitlin JD. Aceruloplasminemia: molecular characterization of this disorder of iron metabolism. Proc Natl Acad Sci U S A 1995;92:2539-43.
82. Frieden E, Hsieh HS. Ceruloplasmin: the copper transport protein with essential oxidase activity. Adv Enzymol Relat Areas Mol Biol 1976; 44:187-236.
83. Morita H, Ikeda S, Yamamoto K, et al. Hereditary ceruloplasmin deficiency with hemosiderosis: a clinicopathological study of a Japanese family. Ann Neurol 1995;37:646-56.
84. Miyajima H, Takahashi Y, Kamata T, Shimizu H, Sakai N, Gitlin JD. Use of desferrioxamine in the treatment of aceruloplasminemia. Ann Neurol 1997;41:404-7.
85. Brittenham GM, Farrell DE, Harris JW, et al. Magnetic-susceptibility measurement of human iron stores. N Engl J Med 1982;307:1671-5.
86. Olivieri NF. The β-thalassemias. N Engl J Med 1999;341:99-109.