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Original Article

Iron Overload Disorders: Natural History, Pathogenesis, Diagnosis, and Therapy

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Pages 205-266 | Published online: 02 Jul 2009

References

  • Fairbanks V. F., Fahey J. L., Beutler E. Clinical Disorders of Iron Metabolism, 2nd ed. Grune & Stratton, New York 1971; 399
  • Walker R. J., Williams R. Haemochromatosis and iron overload. Iron in Biochemistry and Medicine, A. Jacobs, M. Worwood. Academic Press, New York 1974; 589
  • Bothwell T. H., Charlton R. W., Cook J. D., Finch C. A. Iron Metabolism in Man. Blackwell Scientific, Oxford 1979; 121
  • Powell L. W., Halliday J. W. Idiopathic haemochromatosis. Iron in Biochemistry and Medicine, A. Jacobs, M. Worwood. Academic Press, New York 1980; Vol. 2: 462
  • Finch S. C., Finch C. A. Idiopathic hemochromatosis, an iron storage disease. A. Iron metabolism in hemochromatosis. Medicine 1955; 34: 381
  • Powell L. W. Changing concepts in haemochromatosis. Postgrad. Med. J. 1970; 46: 200
  • Grace N. D., Powell L. W. Iron storage disorders of the liver. Gastroenterology 1974; 67: 1257
  • Crosby W. H. Hemochromatosis: the unsolved problems. Semin. Hematol. 1977; 14: 135
  • Powell L. W., Bassett M. L., Halliday J. W. Hemochromatosis: 1980 update. Gastroenterology 1980; 78: 374
  • Halliday J. W., Powell L. W. Iron overload. Semin. Hematol. 1982; 19: 42
  • Harrison P. M., Hoare R. J., Hoy T. G., Macara I. G. Ferritin and haemosiderin: structure and function. Iron in Biochemistry and Medicine, A. Jacobs, M. Worwood. Academic Press, New York 1974; 73
  • Wixom R. L., Prutkin L., Munro H. N. Hemosiderin: nature, formation, and significance. Int. Rev. Exp. Pathol. 1980; 22: 193
  • Trousseau A. Glycosurie, diabète sucré. Clinique Médicale de l'Hotel-Dieu de Paris, 2nd ed. Baillière, Paris 1865; Vol. 2: 663
  • Troisier M. Diabète sucré. Bull. Soc. Anat. Paris 1871; 16: 231
  • von Recklinghausen F. D. Ueber Hämochromatose. Tagebl. Versamml. Natur. Arzte, Heidelberg 1889; 62: 324
  • Sheldon J. H. Haemochromatosis. Oxford University Press, London 1935
  • MacDonald R. A. Idiopathic hemochromatosis. A variant of portal cirrhosis and idiopathic hemosiderosis. Arch. Intern. Med. 1961; 107: 606
  • MacDonald R. A. Idiopathic hemochromatosis: acquired or inherited?. Controversy in Internal Medicine, F. J. Ingelfinger, A. S. Relman, M. Finland. W. B. Saunders, Philadelphia 1966; 271
  • Simon M., Bourel M., Genetet B., Fauchet R. Idiopathic hemochromatosis: demonstration of recessive transmission and early detection by family HLA typing. N. Engl. J. Med. 1977; 297: 1017
  • Cartwright G. E., Edwards C. Q., Kravitz K., Skolnick M., Amos D. B., Johnson A., Buskjaer L. Hereditary hemochromatosis; phenotypic expression of the disease. N. Engl. J. Med. 1979; 301: 175
  • Higginson J., Gerritsen T., Walker A. R. P. Siderosis in the Bantu of Southern Africa. Am. J. Pathol. 1953; 29: 779
  • Bothwell T. H., Abrahams C., Bradlow B. A., Charlton R. W. Idiopathic and Bantu hemochromatosis. Comparative histological study. Arch. Pathol. 1965; 79: 163
  • Strachan A. S. Haemosiderosis and Haemochromatosis in Southern African Natives, with a Comment on the Aetiology of Haemochromatosis. M.D. thesis, Glasgow 1929
  • Walker A. R. P., Arvidsson U. B. Iron uptake and haemochromatosis in Bantu. Nature (London) 1950; 166: 438
  • Bothwell T. H., Bradlow B. A. Siderosis in the Bantu. A combined histopathological and chemical study. Arch. Pathol. 1960; 70: 279
  • Seftel H. C., Keeley K. J., Isaacson C., Bothwell T. H. Siderosis in the Bantu: the clinical incidence of hemochromatosis in diabetic subjects. J. Lab. Clin. Med. 1961; 58: 837
  • Iancu T. C., Lichterman L., Neustein H. B. Hepatic sinusoidal cells in iron overload: ultrastructural observations. Isr. J. Med. Sci. 1978; 14: 1191
  • Perkins K. W., McInnes I. W. S., Blackburn C. R. B., Beal R. W. Idiopathic haemochromatosis in children. Report of a family. Am. J. Med. 1965; 39: 118
  • Ross C. E., Muir W. A., Ng A. B. P., Graham R. C., Jr., Kellermeyer R. W. Hemochromatosis: pathologic and genetic considerations. Am. J. Clin. Pathol. 1975; 63: 179
  • Charlton R. W., Abrahams C., Bothwell T. H. Idiopathic hemochromatosis in young subjects. Clinical, pathological and chemical findings in four patients. Arch. Pathol. 1967; 83: 132
  • Lamon J. M., Marynick S. P., Rosenblatt R., Donnelly S. Idiopathic hemochromatosis in a young female. A case study and review of the syndrome in young people. Gastroenterology 1979; 76: 178
  • Kent G., Popper H. Liver biopsy in diagnosis of hemochromatosis. Am. J. Med. 1968; 44: 837
  • Williams R. Haemochromatosis, I. A. D. Bouchier. Pitman Medical, London 1971; 199, in 7th Symp. Advanced Medicine
  • Knauer C. M., Gamble C. N., Monroe L. S. The reversal of hemochromatotic cirrhosis by multiple phlebotomies. Report of a case. Gastroenterology 1965; 49: 667
  • Weintraub L. R., Conrad M. E., Crosby W. H. The treatment of hemochromatosis by phlebotomy. Med. Clin. N. Am. 1966; 50: 1579
  • Powell L. W., Kerr J. F. R. Reversal of “cirrhosis” in idiopathic haemochromatosis following long-term intensive venesection therapy. Aust. Am. Med. 1970; 1: 54
  • Bomford A., Williams R. Long-term results of venesection therapy in idiopathic haemochromatosis. Q. J. Med. n.s. 1976; 45: 611
  • Warren S., Drake W. L., Jr. Primary carcinoma of the liver in hemochromatosis. Am. J. Pathol. 1951; 27: 573
  • Edmondson H. A., Steiner P. E. Primary carcinoma of the liver; study of 100 cases among 48,900 necropsies. Cancer 1954; 7: 462
  • MacDonald R. A., Mallory G. K. Hemochromatosis and hemosiderosis. Study of 211 autopsied cases. Arch. Intern. Med. 1960; 105: 686
  • Hurst P. E., Kakulas B. A., Walters M. N. I. Hepatoma developing in treated hemochromatosis. Report of a case. Med. J. Aust. 1961; 2: 18
  • Hines C., Jr., Davis W. D., Jr., Ferrante W. A. Hepatoma developing in hemochromatosis in spite of adequate treatment by multiple phlebotomies. Am. J. Dig. Dis. n.s. 1971; 16: 349
  • Abe K., Nicholson W. E., Liddle G. W., Orth D. N., Island D. P. Normal and abnormal regulation of β-MSH in man. J. Clin. Invest. 1969; 48: 1580
  • Dymock I. W., Cassar J., Pyke D. A., Oakley W. G., Williams R. Observations on the pathogenesis, complications and treatment of diabetes in 115 cases of haemochromatosis. Am. J. Med. 1972; 52: 203
  • Eskind I. B., Franklin W., Lowell F. C. Insulin-resistant diabetes mellitus associated with hemochromatosis. Ann. Intern. Med. 1953; 38: 1295
  • Oakley W., Field J. B., Sowton G. E., Rigby B., Cunliffe A. C. Action of prednisone in insulin-resistant diabetes. Br. Med. J. 1959; 1: 1601
  • Bierens de Haan B., Scherrer J. R., Stauffacher W., Pometta D. Iron excess, early glucose intolerance and impaired insulin secretion in idiopathic hemochromatosis. Eur. J. Clin. Invest. 1973; 3: 179
  • Rowe J. W., Wands J. R., Mezey E., Waterbury L. A., Wright J. R., Tobin J., Andres R. Familial hemochromatosis: characteristics of the pre-cirrhotic stage in a large kindred. Medicine 1977; 56: 197
  • Griffiths J. D., Dymock I. W., Davies E. W. G., Hill D. W., Williams R. Occurrence and prevalence of diabetic retinopathy in hemochromatosis. Diabetes 1971; 20: 766
  • Bourel M., Simon M., Ferrand B., Pawlotsky Y., Lenoir P. Quatre observations de pancréatite calcifiante dans l'hémochromatose. Sem. Hôp. Paris 1970; 46: 879
  • Kramer J. R., Jr., Faimer R. G. Idiopathic hemochromatosis presenting as malabsorption syndrome. Cleveland Clin. Q. 1970; 37: 151
  • Stocks A. E., Martin F. I. R. Pituitary function in haemochromatosis. Am. J. Med. 1968; 45: 839
  • Harris P. W. Endocrine abnormalities in chronic liver disease. Guys Hosp. Rep. 1969; 118: 387
  • Stocks A. E., Powell L. W. Pituitary function in idiopathic haemochromatosis and cirrhosis of the liver. Lancet 1972; 2: 298
  • Bezwoda W. R., Bothwell T. H., van der Walt L. A., Kronheim S., Pimstone B. L. An investigation into gonadal dysfunction in patients with idiopathic hemochromatosis. Clin. Endocrinol. 1977; 6: 377
  • Althausen T. L., Doig R. K., Weiden S., Motterann R., Turner C. N., Moore A. Hemochromatosis: investigation of 23 cases, with special reference to etiology, nutrition, iron metabolism, and studies of hepatic and pancreatic function. Arch. Intern. Med. 1951; 88: 553
  • Schumacher H. R., Jr. Hemochromatosis and arthritis. Arthritis Rheum. 1964; 7: 41
  • Walker R. J., Dymock I. W., Ansell I. D., Hamilton E. B. D., Williams R. Synovial biopsy in haemochromatosis arthropathy: histological findings and iron deposition in relation to total body iron overload. Ann. Rheum. Dis. 1972; 31: 98
  • Jensen P. S. Hemochromatosis: a disease often silent but not invisible. Am. J. Roentgenol. 1976; 126: 343
  • Angevine C. D., Jacox R. F. Unusual connective tissue manifestations of hemochromatosis. Arthritis Rheum. 1974; 17: 477
  • Bensen W. G., Laskin C. A., Little H. A., Fam A. G. Hemochromatotic arthropathy mimicking rheumatoid arthritis. A case with subcutaneous nodules, tenosynovitis, and bursitis. Arthritis Rheum. 1978; 21: 844
  • Gordon D. A., Little H. A. The arthropathy of hemochromatosis without hemochromatosis. Arthritis Rheum. 1973; 16: 305
  • M'Seffar A., Fornasier V. L., Fox I. H. Arthropathy as the major clinical indicator of occult iron storage disease. J. Am. Med. Assoc. 1977; 238: 1825
  • Laborde J. M., Green D. L., Askari A. D., Muir A. Arthritis in hemochromatosis. A case report. J. Bone Joint Surg. (Am.) 1977; 59: 1103
  • Rosner I. A., Askari A. D., McLaren G. D., Muir W. A. Arthropathy, hypouricemia and normal serum iron studies in hereditary hemochromatosis. Am. J. Med. 1981; 70: 870
  • Budiman-Mak E., Weitzner R., Lertratanakul Y. Arthropathy of hemochromatosis. Arthritis Rheum. 1977; 20: 1430
  • Stubbins C. Hemochromatosis and arthritis. Proc. R. Soc. Med. 1976; 69: 26
  • Hamilton E. B. D., Bomford A. B., Laws J. W., Williams R. The natural history of arthritis in idiopathic haemochromatosis: progression of the clinical and radiological features over ten years. Q. J. Med. n.s. 1981; 199: 321
  • Seftel H. C., Malkin C., Schmaman A., Abrahams C., Lynch S. R., Charlton R. W., Bothwell T. H. Osteoporosis, scurvy, and siderosis in Johannesburg Bantu. Br. Med. J. 1966; 1: 642
  • Wapnick A. A., Lynch S. R., Krawitz P., Seftel H. C., Charlton R. W., Bothwell T. H. Effects of iron overload on ascorbic acid metabolism. Br. Med. J. 1968; 3: 704
  • Cohen A., Cohen I. J., Schwartz E. Scurvy and altered iron stores in thalassemia major. N. Engl. J. Med. 1981; 304: 158
  • Lynch S. R., Seftel H. C., Torrance J. D., Charlton R. W., Bothwell T. H. Accelerated oxidative catabolism of ascorbic acid in siderotic Bantu. Am. J. Clin. Nutr. 1967; 20: 641
  • Hankes L. V., Jansen C. R., Schmaeler M. Ascorbic acid catabolism in Bantu with hemosiderosis (scurvy). Biochem. Med. 1974; 9: 244
  • Wapnick A. A., Lynch S. R., Seftel H. C., Charlton R. W., Bothwell T. H. The effect of siderosis and ascorbic acid depletion on bone metabolism, with special reference to osteoporosis in the Bantu. Br. J. Nutr. 1971; 25: 367
  • Lynch S. R., Seftel H. C., Wapnick A. A., Charlton R. W., Bothwell T. H. Some aspects of calcium metabolism in normal and osteoporotic Bantu subjects with special reference to the effects of iron overload and ascorbic acid depletion. S. Afr. J. Med. Sci. 1970; 35: 45
  • Keschner H. W. The heart in hemochromatosis. South. Med. J. 1951; 44: 927
  • Buja L. M., Roberts W. C. Iron in the heart. Am. J. Med. 1970; 51: 209
  • McAllen P. M., Coghill N. F., Lubran M. The treatment of haemochromatosis; with particular reference to the removal of iron from the body by repeated venesection. Q. J. Med. n.s. 1957; 26: 251
  • Grosberg S. J. Hemochromatosis and heart failure: presentation of a case with survival after three years' treatment by repeated venesection. Ann. Intern. Med. 1961; 54: 550
  • Easley R. M., Schreiner B. F., Yu P. N. Reversible cardiomyopathy associated with hemochromatosis. N. Engl. J. Med. 1972; 287: 866
  • Skinner C., Kenmure A. C. F. Haemochromatosis presenting as congestive cardiomyopathy and responding to venesection. Br. Heart J. 1973; 35: 466
  • Schafer A. I., Cheron R. G., Dluhy R., Cooper B., Gleason R. E., Soeldner J. S., Bunn H. F. Clinical consequences of acquired transfusional iron overload in adults. N. Engl. J. Med. 1981; 304: 319
  • de Alarcon P. A., Donovan M. A., Forbes G. B., Landaw S. E., Stockman J. A., III. Iron absorption in the thalassemia syndromes and its inhibition by tea. N. Engl. J. Med. 1979; 300: 5
  • McClatchie S., Taylor H. E., Henry A. T. Acute abdominal pain and shock associated with hemochromatosis. Can. Med. Assoc. J. 1950; 63: 485
  • MacSween R. N. M. Acute abdominal crisis, circulatory collapse and sudden death in haemochromatosis. Q. J. Med. n.s. 1966; 35: 589
  • Yamashiro K. W., Goldman R. H., Harris D. R., Uyeda C. T. Pasteurella pseudotuberculosis Acute sepsis with survival. Arch. Intern. Med. 1971; 128: 605
  • Sussman M. Iron and infection. Iron in Biochemistry and Medicine, A. Jacobs, M. Worwood. Academic Press, New York 1974; 650
  • Weinberg E. D. Iron and susceptibility to infectious disease. Science 1974; 184: 952
  • Hegenauer J., Saltman P. Iron and susceptibility to infectious disease. Science 1975; 188: 1038
  • Barry D. M. J., Reeve A. W. Increased incidence of Gram-negative neonatal sepsis with intramuscular iron administration. Pediatrics 1977; 60: 908
  • McFarlane H., Reddy S., Adcock K. J., Adeshina H., Cooke A. R., Akene J. Immunity, transferrin, and survival in kwashiorkor. Br. Med. J. 1970; 4: 268
  • Cantwell R. J. Iron deficiency anemia of infancy. Some clinical principles illustrated by response of Maori infants to neonatal parenternal iron administration. Clin. Pediatr. 1972; 11: 443
  • Blake P. A., Merson M. H., Weaver R. E., Hollis D. G., Heublein P. C. Disease caused by a marine Vibrio: clinical characteristics and epidemiology. N. Engl. J. Med. 1979; 300: 1
  • Matzner Y., Hershko C., Polliack A., Konijn A. M., Izak G. Suppressive effect of ferritin on in vitro lymphocyte function. Br. J. Haematol. 1979; 42: 345
  • van Asbeck B. S., Verbrugh H. A., van Oost B. A., Marx J. J. M., Imhof H. W., Verhoef J. Listeria monocytogenes meningitis and decreased phagocytosis associated with iron overload. Br. Med. J. 1982; 284: 542
  • McLaren G. D., Konijn A. M., Bentley D. P., Jacobs A. Iron uptake and ferritin synthesis by human peripheral blood monotypes incubated in vitro with a particulate suspension of radioiron. The Biochemistry and Physiology of Iron, J. Hegenauer, P. Saltman. Elsevier, New YorkNorth-Holland 1982; 605
  • Milder M. S., Cook J. D., Stray S., Finch C. A. Idiopathic hemochromatosis, an interim report. Medicine 1980; 59: 34
  • Sullivan L. W., Herbert V. Suppression of hematopoiesis by ethanol. J. Clin. Invest. 1964; 43: 2048
  • Lizzi F. A., Tartaglia A. P., Adamson J. W. Hemochromatosis, hepatoma, erythrocytosis and erythropoietin. N. Y. State J. Med. 1973; 73: 1098
  • Scott D., Theologides A. Hepatoma, erythrocytosis, and increased serum erythropoietin in long-standing hemochromatosis. Am. J. Gastroenterol. 1974; 61: 206
  • Beutler E. Clinical evaluation of iron stores. N. Engl. J. Med. 1957; 256: 692
  • Granick S. Iron metabolism and hemochromatosis. Bull. N.Y. Acad. Med. 1949; 25: 403
  • Popper H. P., Schaffner F. Liver: Structure and Function. McGraw-Hill, New York 1957
  • Brink B., Disler P., Lynch S., Jacobs P., Charlton R., Bothwell T. Patterns of iron storage in dietary iron overload and idiopathic hemochromatosis. J. Lab. Clin. Med. 1976; 88: 725
  • Ammann R. W., Müller E., Bansky J., Schüller G., Häcki W. H. High incidence of extrahepatic carcinomas in idiopathic hemochromatosis. Scand. J. Gastroenterol. 1980; 15: 733
  • Heilmeyer L., Keller W., Vivell O., Keideling W., Betke K., Wohler F., Schultze H. E. Congenital transferrin deficiency in a 7-year-old girl. Germ. Med. Monthly 1961; 6: 385
  • Goya N., Miljazaki S., Kodate S., Vshio B. A family of congenital atransferrinemia. Blood 1972; 40: 239
  • Ellis J. T., Schulman I., Smith C. H. Generalized siderosis with fibrosis of the liver and pancreas in Cooley's (Mediterranean) Anemia. Am. J. Pathol. 1954; 30: 287
  • Byrd R. B., Cooper T. Hereditary iron loading anemia with secondary hemochromatosis. Ann. Intern. Med. 1961; 55: 103
  • Bothwell T. H., Cohen I., Abrahams O. L., Perold S. M. A familial study in idiopathic hemochromatosis. Am. J. Med. 1959; 27: 730
  • Nussbaumer T., Platner H. R., Rywlin A. Hemochromatose juvenile chez trois soeurs et un frère avec consanguinité des parents. J. Genet. Hum. 1952; 1: 139
  • Brick I. B. Liver histology in six asymptomatic siblings in a family with hemochromatosis. Genetic implications. Gastroenterology 1961; 40: 210
  • Scheuer P. J., Williams R., Muir A. R. Hepatic pathology in relatives of patients with hemochromatosis. J. Pathol. Bacteriol. 1962; 84: 53
  • Dillingham C. H. Familial occurrence of hemochromatosis. N. Engl. J. Med. 1960; 262: 1128
  • Johnson G. B., Frey W. G. Familial aspects of idiopathic hemochromatosis. J. Am. Med. Assoc. 1962; 179: 747
  • Harris O. D. Haemochromatosis, a family study. Med. J. Aust. 1962; 2: 754
  • Houston J. C., Zilkhak J. Hemochromatosis in a family. Guys Hosp. Rep. 1955; 104: 262
  • Löhr K., Reinwein H. Konkordantes auftreten von lebercirrhose und diabetes mellitus (hämochromatose) bei eineiigen zwillingen. Deutsch. Arch. Klin. Med. 1952; 200: 53, 202–767, 1956
  • Felts J. H., Nelson J. R., Herndon C. N., Spur C. L. Hemochromatosis in two young sisters. Case studies and a family survey. Ann. Intern. Med. 1967; 67: 117
  • Debré R., Dreyfus J.-C., Frézal J., Labie D., Lamy M., Maroteaux P., Schapira F., Schapira G. Genetics of haemochromatosis. Ann. Hum. Genet. 1958; 23: 16
  • Dreyfus J.-C., Schapira G. The metabolism of iron in haemochromatosis. Iron Metabolism: An International Symposium, F. Gross. Springer-Verlag, Berlin 1964; 296
  • Balcerzak S. P., Westerman M. P., Lee R. E., Doyle A. P. Idiopathic hemochromatosis: a study of three families. Am. J. Med. 1966; 40: 857
  • Davison R. H. Inheritance of haemochromatosis: a report on a family with consanguinity. Br. Med. J. 1961; 2: 1262
  • Bothwell T. H., Finch C. A. Iron Metabolism. Little, Brown, Boston 1962; 364
  • Feller E. R., Pont L. A., Wands J. R., Carter E. A., Foster G., Kouirides I. A., Isselbacher K. J. Familial hemochromatosis: physiologic studies in the precirrhotic stage of the disease. N. Engl. J. Med. 1977; 296: 1422
  • Edwards C. Q., Carroll M., Bray P., Cartwright G. E. Hereditary hemochromatosis: diagnosis in siblings and children. N. Engl. J. Med. 1977; 297: 7
  • Simon M., Pawlotsky Y., Bourel M., Fauchet R., Genetet B. Idiopathic hemochromatosis associated with HL-A3 tissular antigen. Nouvelle Presse Med. 1975; 4: 1432
  • Walters J. M., Watt D. W., Stevens F. M., McCarthy C. F. HLA antigens in haemochromatosis. Br. Med. J. 1975; 4: 520
  • Shewan W. G., Mouat S. A., Allen T. M. HLA antigens in haemochromatosis. Br. Med. J. 1976; 1: 281
  • Simon M., Bourel M., Fauchet R., Genetet B. Association of HLA-A3 and HLA-B14 antigens with idiopathic haemochromatosis. Gut 1976; 17: 332
  • Goossens J. P., Schreuder I., Went L. N. Inheritance of idiopathic haemochromatosis. Lancet 1977; 1: 1106
  • MacDonald R. A. Hemochromatosis and Hemosiderosis. Charles C Thomas, Springfield, Ill 1964
  • Simon M., Bourel M., Genetet B., Fauchet R., Edan G., Brissot P. Idiopathic hemochromatosis and iron overload in alcoholic liver disease: differentiation by HLA phenotype. Gastroenterology 1977; 73: 655
  • Muir W. A., McLaren G. D., Braun W. A., Askari A. D. Hereditary hemochromatosis: dominant inheritance and probable linkage to HLA. Am. J. Hum. Genet. 1978; 30: 61A
  • Lipinski M., Hors J., Saleun J., Saddi R., Passa P., Lafaurie S., Feingold N., Dausset J. Idiopathic hemochromatosis: linkage with HLA. Tissue Antigens 1978; 11: 471
  • Beaumont C., Simon M., Fauchet R., Hespel J.-P., Brissot P., Genetet B., Bourel M. Serum ferritin as a possible marker of the hemochromatosis allele. N. Engl. J. Med. 1979; 301: 169
  • Edwards C. Q., Cartwright G. E., Skolnick M. H., Amos D. B. Genetic mapping of the hemochromatosis locus on chromsome six. Hum. Immunol. 1980; 1: 19
  • MacSween R. N. M., Scott A. R. Hepatic cirrhosis: a clinico-pathologic review of 520 cases. J. Clin. Pathol. 1973; 26: 936
  • Simon M., Alexandre J.-L., Fauchet R., Genetet B., Bourel M. The genetics of hemochromatosis. Prog. Med. Genet. 1980; 4: 135
  • Motulsky A. G. Genetics of hemochromatosis. N. Engl. J. Med. 1979; 301: 1291
  • Bomford A., Eddleston A. L. W.F., Kennedy L. A., Batchelor J. R., Williams R. Histocompatibility antigens as markers of abnormal iron metabolism in patients with idiopathic haemochromatosis and their relatives. Lancet 1977; 1: 327
  • Simon M., Fauchet R., Hespel J. P., Beaumont C., Brissot P., Hery B., de Nercy Y. H., Genetet B., Bourel M. Idiopathic hemochromatosis: a study of biochemical expression in 247 heterozygous members of 63 families: evidence for a single major HLA-linked gene. Gastroenterology 1980; 78: 703
  • Aronow W. S., Meister L., Kent J. R. Atrioventricular block in familial hemochromatosis treated by permanent synchronous pacemaker. Arch. Intern. Med. 1969; 123: 433
  • Chapman R. W., Morgan M. Y., Laulicht M., Hoffbrand A. V., Sherlock S. Hepatic iron stores and markers of iron overload in alcoholics and patients with idiopathic hemochromatosis. Dig. Dis. Sci. 1982; 27: 909
  • Felsher B. F., Kushner J. P. Hepatic siderosis and porphyria cutanea tarda: relation of iron excess to the metabolic defect. Semin. Hematol. 1977; 14: 243
  • Grossman M. E., Bickers D. R., Poh-Fitzpatrick M. B., Deleo V. A., Harber L. C. Porphyria cutanea tarda: clinical features and laboratory findings in 40 patients. Am. J. Med. 1979; 67: 277
  • Ippen H. Treatment of porphyria cutanea tarda by phlebotomy. Semin. Hematol. 1977; 14: 253
  • Kushner J. P., Barbuto A. J., Lee G. R. An inherited enzymatic defect in porphyria cutanea tarda: decreased uroporphyrinogen decarboxylase activity. J. Clin. Invest. 1976; 58: 1089
  • Elder G. H., Lee G. B., Tovey J. A. Decreased activity of hepatic uroporphyrinogen decarboxylase in sporadic porphyria cutanea tarda. N. Engl. J. Med. 1978; 299: 274
  • Felsher B. F., Carpio N. M., Engleking D. W., Nunn A. T. Decreased hepatic uroporphyrinogen decarboxylase activity in porphyria cutanea tarda. N. Engl. J. Med. 1982; 306: 766
  • Kushner J. P. The enzymatic defect in porphyria cutanea tarda. N. Engl. J. Med. 1982; 306: 799
  • Felsher B. F., Norris M. E., Shih J. C. Red-cell uroporphyrinogen decarboxylase activity in porphyria cutanea tarda and in other forms of porphyria. N. Engl. J. Med. 1978; 299: 1095
  • Kushner J. P., Steinmuller D. P., Lee G. R. The role of iron in the pathogenesis of porphyria cutanea tarda. II. Inhibition of uroporphyrinogen decarboxylase. J. Clin. Invest. 1975; 56: 661
  • Benedetto A. V., Kushner J. P., Taylor J. S. Porphyria cutanea tarda in three generations of a single family. N. Engl. J. Med. 1978; 298: 358
  • Kuntz B. M. E., Goerz G., Sonneborn H. H., Lissner R. HLA-types in porphyria cutanea tarda. Lancet 1981; 1: 155
  • Bregman H., Gelfand M. C., Winchester J. F., Manz H. J., Knepshield J. H., Schreiner G. E. Iron-overload-associated myopathy in patients on maintenance haemodialysis: a histocompatibility-linked disorder. Lancet 1980; 2: 882
  • Powell L. W., Halliday J. W. Iron absorption and iron overload. Clin. Gastroenterol. 1981; 10: 707
  • Layrisse M., Martinez-Torres C., Renzy M., Leets I. Ferritin iron absorption in man. Blood 1975; 45: 689
  • Heinrich H. C., Gabbe E. E., Kugler G. Iron absorption from ingested pork, hog-liver and hemoglobin in subjects with normal and depleted iron stores. Studies on dietary iron prophylaxis and therapy. Klin. Wochenschr. 1971; 49: 819
  • Heinrich H. C. Clinical aspects of iron absorption and turnover. Iron Metabolism and Its Disorders, H. Kief. Elsevier, New York 1975; 34
  • Heinrich H. C. Gastric intrinsic factor and iron absorption. Lancet 1970; 2: 1256
  • Wheby M. S. Site of iron absorption in man. Scand. J. Haematol. 1970; 7: 56
  • McCance R. A., Widdowson E. M. Absorption and excretion of iron. Lancet 1937; 2: 680
  • Granick S. Ferritin: its properties and significance for iron metabolism. Chem. Rev. 1946; 38: 379
  • Huebers H., Huebers E., Rummel W. Mechanism of iron absorption: iron-binding proteins and dependence of iron absorption on an elutable factor. Iron Metabolism and Its Disorders, H. Kief. Elsevier, New York 1975; 13
  • Deutschländer N., Kief H., Bähr H. Morphological findings in iron absorption. Iron Metabolism and Its Disorders, H. Kief. Elsevier, New York 1975; 6
  • Cavill I., Worwood M., Jacobs A. Internal regulation of iron absorption. Nature (London) 1975; 256: 328
  • Rosenmund A., Gerber S., Heubers H., Finch C. Regulation of iron absorption and storage iron turnover. Blood 1980; 56: 30
  • Williams R., Manenti F., Williams H. S., Pitcher C. S. Iron absorption in idiopathic haemochromatosis before, during, and after venesection therapy. Br. Med. J. 1966; 2: 78
  • Walters G. O., Jacobs A., Worwood M., Trevett D., Thomson W. Iron absorption in normal subjects and patients with idiopathic haemochromatosis: relationship with serum ferritin concentration. Gut 1975; 16: 188
  • Davis A. E. Relationship of disturbed pancreatic function to haemosiderosis. Lancet 1961; 2: 749
  • Biggs J. C., Davis A. E. Relationship of diminished pancreatic secretion to haemochromatosis. Lancet 1963; 2: 814
  • Murray M. J., Stein N. Does the pancreas influence iron absorption? A critical review of information to date. Gastroenterology 1966; 51: 694
  • Smith J. A., Drysdale J. W., Goldberg A., Munro H. N. The effect of enteral and parenteral iron on ferritin synthesis in the intestinal mucosa of the rat. Br. J. Haematol. 1968; 14: 79
  • Davis P. S., Luke C. G., Deller D. J. Reduction of gastric iron-binding protein in haemochromatosis, a previously unrecognized metabolic defect. Lancet 1966; 2: 1431
  • Luke C. G., Davis P. S., Deller D. J. Gastric iron binding in haemochromatosis, secondary iron overload, cirrhosis, and diabetes. Lancet 1968; 2: 844
  • Deller D. J., Edwards R. G., Dart G., Luke C. G., Davis P. S. Gastric iron binding substance (gastroferrin) in a family with haemochromatosis. Aust. Ann. Med. 1969; 18: 36
  • Wynter C. V. A., Williams R. Iron binding properties of gastric juice in idiopathic haemochromatosis. Lancet 1968; 2: 534
  • Morgan O. S., Weir D. G., Gatenby P. B. B., Scott J. M. Studies on an iron-binding component in human gastric juice. Lancet 1969; 1: 861
  • Powell L. W., Wilson E. In vivo intestinal mucosal uptake of iron, body iron and absorption and gastric juice iron-binding in idiopathic haemochromatosis. Aust. Ann. Med. 1970; 3: 226
  • Crosby W. H. The control of iron balance by the intestinal mucosa. Blood 1963; 22: 441
  • Astaldi G., Meardi G., Lisino T. The iron content of jejunal mucosa obtained by Crosby's biopsy in hemochromatosis and hemosiderosis. Blood 1966; 28: 70
  • Boender C. A., Verloop M. C. Iron absorption, iron loss and iron retention in man: studies after oral administration of a tracer dose of 59FeSO4131BaSo4. Br. J. Haematol. 1969; 17: 45
  • Powell L. W., Campbell C. B., Wilson E. Intestinal mucosal uptake of iron and iron retention in idiopathic haemochromatosis as evidence for a mucosal abnormality. Gut 1970; 11: 727
  • Ayvazian J. H. Xanthinuria and hemochromatosis. N. Engl. J. Med. 1964; 270: 18
  • Mazur A., Green S., Saha A., Carleton A. Mechanism of release of ferritin iron in vivo by xanthine oxidase. J. Clin. Invest. 1958; 37: 1809
  • Dawson R. B., Rafal S., Weintraub L. R. Absorption of hemoglobin iron: the role of xanthine oxidase in the intestinal heme-splitting reaction. Blood 1970; 35: 94
  • Davis P. S., Deller D. J. Effect of xanthine oxidase inhibitor (allopurinol) on radioiron absorption in man. Lancet 1966; 2: 470
  • Cox T. M., Peters T. J. The kinetics of iron uptake in vitro by human duodenal mucosa: studies in normal subjects. J. Physiol. 1979; 289: 469
  • Cox T. M., Peters T. J. Cellular mechanisms in the regulation of iron absorption by the human intestine: studies in patients with iron deficiency before and after treatment. Br. J. Haematol. 1980; 44: 75
  • Cox T. M., Peters T. J. Uptake of iron by duodenal biopsy specimens from patients with iron-deficiency anaemia and primary haemochromatosis. Lancet 1978; 1: 123
  • Cox T. M., Peters T. J. In vitro studies of duodenal iron uptake in patients with primary and secondary iron storage disease. Q. J. Med. n.s. 1980; 49: 249
  • Cox T. M. Prevalence of the hemochromatosis gene. N. Engl. J. Med. 1980; 302: 695
  • Marx J. J. M. Mucosal uptake, mucosal transfer, and retention of iron, measured by whole body counting. Scand. J. Haematol. 1979; 23: 293
  • Cook J. D., Barry W. E., Hershko C., Fillet G., Finch C. A. Iron kinetics with emphasis on iron overload. Am. J. Pathol. 1973; 72: 337
  • Brown E. B., Okada S., Awai M., Chipman B. In vivo evidence for the functional heterogeneity of transferrin-bound iron. III. Studies of transferrin at high and low saturation. J. Lab. Clin. Med. 1975; 86: 576
  • Zimelman A. P., Zimmerman H. J., McLean R., Weintraub L. R. Effect of iron saturation of transferrin on hepatic iron uptake: an in vitro study. Gastroenterology 1977; 72: 129
  • Aisen P., Brown E. B. The iron-binding function of transferrin in iron metabolism. Semin. Hematol. 1977; 14: 31
  • Morgan E. H., Huebers H., Finch C. A. Differences between the binding sites for iron binding and release in human and rat transferrin. Blood 1978; 52: 1219
  • Lynch S. R., Simon M., Bothwell T. H., Charlton R. W. Circadian variation in plasma iron concentration and reticuloendothelial iron release in the rat. Clin. Sci. Mol. Med. 1973; 45: 331
  • Sinniah R., Doggart J. R., Neill D. W. Diurnal variations of the serum iron in normal subjects and in patients with haemochromatosis. Br. J. Haematol. 1969; 17: 351
  • Evans R. W., Williams J., Moreton K. M. A transferrin variant with unusual iron-binding properties. Proc. 4th Int. Conf. Proteins of Iron Metabolism. Davos, Switzerland 1979
  • Bothwell T. H., Jacobs P., Torrance J. D. Studies on the behaviour of transferrin in idiopathic haemochromatosis. S. Afr. J. Med. Sci. 1962; 27: 35
  • Batey R. G., Fong P. L. C., Schamir S., Sherlock S. A nontransferrin-bound serum iron in idiopathic hemochromatosis. Dig. Dis. Sci. 1980; 25: 340
  • Hershko C., Graham G., Bates G. W., Rachmilewitz E. A. Nonspecific serum iron in thalassaemia: an abnormal serum iron fraction of potential toxicity. Br. J. Haematol. 1978; 40: 255
  • Ricketts C., Cavill I. Iron kinetics and erythropoiesis. Iron Metabolism. Excerpta Medica, Amsterdam 1977; 145, Ciba Found. Symp. 51
  • Batey R. G., Pettit J. E., Nicholas A. W., Sherlock S., Hoffbrand A. V. Hepatic iron clearance from serum in treated hemochromatosis. Gastroenterology 1978; 75: 856
  • Pollycove M., Fawwaz R. A., Winchell H. S. Transient hepatic deposition of iron in primary hemochromatosis with iron deficiency following venesection. J. Nucl. Med. 1971; 12: 28
  • Fawwaz R. A., Winchell H. S., Pollycove M., Sargent T. Hepatic iron deposition in humans. Blood 1967; 30: 417
  • Valberg L. S., Simon J. B., Manley P. N., Corbett W. E., Ludwig J. Distribution of storage iron as body iron stores expand in patients with hemochromatosis. J. Lab. Clin. Med. 1975; 86: 479
  • Tavill A. S., Morton A. G. Transferrin metabolism and the liver. Metals and the Liver, L. W. Powell. Marcel Dekker, New York 1978; 93
  • Clegg G. A., Fitton J. E., Harrison P. M., Treffry A. Ferritin: molecular structure and iron-storage mechanisms. Prog. Biophys. Mol. Biol. 1980; 36: 53
  • Harrison P. M., Clegg G. A., May K. Ferritin structure and function. Iron in Biochemistry and Medicine, A. Jacobs, M. Worwood. Academic Press, London 1980; Vol. 2: 131
  • Crichton R. R., Collet-Cassart D., Ponce-Ortiz Y., Wauters M., Roman F., Paques E. Ferritin: comparative structural studies, iron deposition, and mobilization. Proteins of Iron Metabolism, E. B. Brown, P. Aisen, J. Fielding, R. R. Crichton. Grune & Stratton, New York 1977; 13
  • Jacobs A. Iron overload—clinical and pathologic aspects. Semin. Hematol. 1977; 14: 89
  • Jacobs A. The pathology of iron overload. Iron in Biochemistry and Medicine, A. Jacobs, M. Worwood. Academic Press, London 1980; Vol. 2: 427
  • Harrison P. M. Ferritin: an iron-storage molecule. Semin. Hematol. 1977; 14: 55
  • Drysdale J. W., Adelman T. G., Arosio P., Casareale D., Fitzpatrick P., Hazard J. T., Yokota M. Human isoferritins in normal and disease states. Semin. Hematol. 1977; 14: 71
  • Gabuzda T. G., Pearson J. Metabolic and molecular heterogeneity of marrow ferritin. Biochim. Biophys. Acta. 1969; 194: 50
  • Wagstaff M., Worwood M., Jacobs A. Properties of human tissue isoferritins. Biochem. J. 1978; 173: 969
  • Worwood M., Jones B. M., Jacobs A. The reactivity of isoferritins in a labelled antibody assay. Immunochemistry 1976; 13: 477
  • Hoy T. G., Jacobs A. Changes in the characteristics and distribution of ferritin in iron-loaded cell cultures. Biochem. J. 1981; 193: 87
  • Drysdale J. W. Ferritin phenotypes: structure and metabolism. Iron Metabolism. Excerpta Medica, Amsterdam 1977; 41, Ciba Found. Symp. 51
  • Crichton R. R., Millar J. A., Cumming R. L. C., Bryce C. F. A. The organ-specificity of ferritin in human and horse liver and spleen. Biochem. J. 1973; 131: 51
  • Powell L. W., Alpert E., Isselbacher K. J., Drysdale J. W. Abnormality in tissue isoferritin distribution in idiopathic haemochromatosis. Nature (London) 1974; 250: 333
  • Powell L. W., McKerring L. V., Halliday J. W. Alterations in tissue ferritins in iron storage disorders. Gut 1975; 16: 909
  • Fineberg R. A., Greenberg D. M. Ferritin biosynthesis. II. Acceleration of synthesis by the administration of iron. J. Biol. Chem. 1955; 214: 97
  • Drysdale J. W., Shafritz D. A. In vitro stimulation of apoferritin synthesis by iron. Biochem. Biophys. Acta 1975; 383: 97
  • Jacobs A. Low molecular weight intracellular iron transport compounds. Blood 1977; 50: 433
  • Lynch S. R., Lipschitz D. A., Bothwell T. H., Charlton R. W. Iron and the reticuloendothelial system. Iron in Biochemistry and Medicine, A. Jacobs, M. Worwood. Academic Press, New York 1974; 563
  • Beamish M. R., Walker R., Miller F., Worwood M., Jacobs A., Williams R., Corrigall A. Transferrin iron, chelatable iron and ferritin in idiopathic haemochromatosis. Br. J. Haematol. 1974; 27: 219
  • Valberg L. S. Tissue iron distribution in idiopathic hemochromatosis. Gastroenterology 1978; 75: 915
  • Selden C., Owen M., Hopkins J. M. P., Peters T. J. Studies on the concentration and intracellular localization of iron proteins in liver biopsy specimens from patients with iron overload with special reference to their role in lysosomal disruption. Br. J. Haematol. 1980; 44: 593
  • Halliday J. W., Mack U., Powell L. W. Duodenal ferritin content and structure: relationship with body iron stores in man. Arch. Intern. Med. 1978; 138: 1113
  • Jacobs A., Summers M. R. Iron uptake and ferritin synthesis by peripheral blood leucocytes in patients with primary idiopathic haemochromatosis. Br. J. Haematol. 1981; 49: 649
  • Bassett M. L., Halliday J., Powell L. W. Ferritin synthesis in peripheral blood monocytes in idiopathic hemochromatosis. J. Lab. Clin. Med. 1982; 100: 137
  • Powell L. W., Kerr J. F. R. The pathology of the liver in hemochromatosis. Pathobiol. Annu. 1975; 5: 317
  • Brittenham G. M., Danish E. H., Harris J. W. Assessment of bone marrow and body iron stores: old techniques and new technologies. Semin. Hematol. 1981; 18: 194
  • Gale E., Torrance J., Bothwell T. The quantitative estimation of total iron stores in human bone marrow. J. Clin. Invest. 1963; 42: 1076
  • Block M. B., Moore G., Wasi P., Haiby G. Histogenesis of the hepatic lesion in primary hemochromatosis: with consideration of the pseudo-iron deficient state produced by phlebotomies. Am. J. Pathol. 1965; 47: 89
  • Nixon R. K., Olson J. P. Diagnostic value of marrow hemosiderin patterns. Ann. Intern. Med. 1968; 69: 1249
  • Cooperberg A. A., Rosenberg A., Schwartz J. P. Diagnostic value of bone marrow iron deposits in idiopathic hemochromatosis. Arch. Intern. Med. 1977; 137: 748
  • MacDonald R. A., Endo H., Pechet G. S. Studies of experimental hemochromatosis: disorder of the reticuloendothelial system and excess iron. Arch. Pathol. 1968; 85: 366
  • McLaren G. D., Boehm C., Muir W. A. Decreased uptake of iron by peripheral blood monocytes from patients with hereditary hemochromatosis. A clue to etiology? Blood 1979; 54(1)43a
  • Erickson R. P. Haemochromatosis and superoxide metabolism: free-radical influenced iron storage?. Lancet 1978; 2: 743
  • Hershko C. Storage iron regulation. Progress in Hematology. Grune & Stratton, New York 1977; Vol. 10: 105
  • Pitcher C. S., Williams H. S., Parsonson A., Williams R. The measurement of iron absorption by the double isotope technique. Br. J. Haematol. 1965; 11: 633
  • Smith P. M., Godfrey B. E., Williams R. Iron absorption in idiopathic haemochromatosis and its measurement using a whole-body counter. Clin. Sci. 1969; 37: 519
  • Bezwoda W. R., Disler S. R., Lynch R. W., Charlton R. W., Torrance J. D., Derman D., Bothwell T. H., Walker R. B., Mayet F. Patterns of food iron absorption in iron-deficient white and Indian subjects and in venesected haemochromatotic patients. Br. J. Haematol. 1976; 33: 425
  • Sargent T., Saito H., Winchell H. S. Iron absorption in hemochromatosis before and after phlebotomy therapy. J. Nucl. Med. 1971; 12: 660
  • Dymock I. W., Smith P. M., Williams R. Iron absorption studies in idiopathic haemochromatosis. Br. J. Radiol. 1970; 43: 284
  • Schumacher H. R., Jr. Ultrastructural characteristics of the synovial membrane in idiopathic haemochromatosis. Ann. Rheum. Dis. 1972; 31: 465
  • Muriden K. G. Ferritin in synovial cells in patients with rheumatoid arthritis. Ann. Rheum. Dis. 1966; 25: 387
  • Yam L. T., Finkel H. E., Weintraub L. R., Crosby W. H. Circulating iron-containing macrophages in hemochromatosis. N. Engl. J. Med. 1968; 279: 512
  • Green R., Saab G. A., Conjalka M. S., Crosby W. H. Monocyte ferritin levels disproportionately low in untreated idiopathic hemochromatosis. Blood 1978; 52(1)80
  • Fillet G., Marsaglia G. Idiopathic hemochromatosis (IH). Abnormality in RBC transport of iron by the reticuloendothelial system (RES). Blood 1975; 46: 1007, (Abstr. 19)
  • Cavill I., Bentley D. P., Stefanelli M., personal communication
  • Bentley D. P., Cavill I., Ricketts C., Peake S. A method for the investigation of reticuloendothelial iron kinetics in man. Br. J. Haematol. 1979; 43: 619
  • Hausmann K., Kuse R. Morphological types of non-heme iron in bone marrow squash preparations and intestinal iron absorption. Iron Deficiency, L. Hallberg, H. G. Harwerth, A. Vanotti. Academic Press, New York 1970; 297
  • Crosby W. H. Iron and the macrophage. The monocyte is a metabolic idiot. Arch. Intern. Med. 1982; 142: 233
  • Brown E. B., Dubach R., Smith D. E., Reynafarje C., Moore C. V. Studies in iron transportation and metabolism. X. Long-term iron overload in dogs. J. Lab. Clin. Med. 1957; 50: 862
  • Kinney T. D., Kaufman N., Klavins J. Effect of ethionine-induced pancreatic damage on iron absorption. J. Exp. Med. 1955; 102: 151
  • MacDonald R. A. Experimental pigment cirrhosis: its production in rats by feeding a choline deficient diet with excess iron. Am. J. Pathol. 1960; 36: 499
  • MacDonald R. A., Pechet G. S. Experimental hemochromatosis in rats. Am. J. Pathol. 1965; 46: 85
  • MacDonald R. A., MacSween R. N. M., Pechet G. S. Iron metabolism by reticuloendothelial cells in vitro: physical and chemical conditions, lipotrope deficiency, and acute inflammation. Lab. Invest. 1969; 21: 236
  • Pechet G. S. Parenteral iron overload. Organ and cell distribution in rats. Lab. Invest. 1969; 20: 119
  • MacSween R. N. M., MacDonald R. A. Iron metabolism by reticuloendothelial cells: in vitro uptake of transferrin-bound iron by rat and rabbit cells. Lab. Invest. 1969; 21: 230
  • Lisboa P. Experimental hepatic cirrhosis in dogs caused by chronic massive iron overload. Gut 1971; 12: 363
  • Richter G. W. Effects of cyclic starvation—feeding and of splenectomy on the development of hemosiderosis in rat livers. Am. J. Pathol. 1974; 74: 481
  • McLaren G. D., Sachs S. D., Muir W. A., Kellermeyer R. W. Canine hemochromatosis: a model for the study of reticuloendothelial cell function. Clin. Res. 1976; 24: 315A
  • McLaren G. D., Muir A., Sachs S., Johnston K. Animal model for hemochromatosis: hereditary susceptibility to hepatocellular iron overload. Proc. 4th Int. Conf. Proteins of Iron Metabolism. Davos, Switzerland 1979
  • Steiner A., Kendall F. E. Atherosclerosis and arteriosclerosis in dogs following ingestion of cholesterol and thiouracil. Arch. Pathol. 1946; 42: 433
  • Winkelmann J. C., Mariash C. N., Towle H. C., Oppenheiner J. H. Thyroidectomy increases rat hepatic ferritin iron. Science 1981; 213: 569
  • Awai M., Narasaki M., Yamanoi Y., Seno S. Induction of diabetes in animals by parenteral administration of ferric nitrilotriacetate. A model of experimental hemochromatosis. Am. J. Pathol. 1979; 95: 663
  • May M. E., Parmley R. T., Spicer S. S., Ravenel D. P., May E. E., Buse M. G. Iron nitrilotriacetate-induced experimental diabetes in rats. J. Lab. Clin. Med. 1980; 95: 525
  • Brittenham G. M., Bacon B. R., Park C. H., Tavill A. S. Iron overload: a new experimental model with oral elemental iron, submitted for publication
  • Richter G. W. The iron-loaded cell—the cytopathology of iron storage. Am. J. Pathol. 1978; 91: 363
  • Goldberg L., Marti L. E., Batchelor A. Biochemical changes in the tissues of animals injected with iron. 3. Lipid peroxidation. Biochem. J. 1962; 83: 291
  • Seymour C. A., Budillon G., Peters T. J. Lysosomal changes in human and experimental iron overload. Gut 1974; 15: 838
  • Peters T. J., Seymour C. A. Acid hydrolase activities and lysosomal integrity in liver biopsies from patients with iron overload. Clin. Sci. Mol. Med. 1976; 50: 75
  • Wills E. D. Lipid peroxide formation in microsomes. The role of non-haem iron. Biochem. J. 1969; 113: 325
  • Wills E. D. Mechanisms of lipid peroxide formation in animal tissues. Biochem. J. 1966; 99: 667
  • Wapnick A. A., Lynch S. R., Charlton R. W., Seftel H. C., Bothwell T. H. The effect of ascorbic acid deficiency on desferrioxamine-induced urinary iron excretion. Br. J. Haematol. 1969; 17: 563
  • Bacon B. R., Tavill A. S., Brittenham G. M., Park C. H., Recknagel R. O. Hepatic lipid peroxidation in vivo in rats with chronic iron overload. J. Clin. Invest. 1983; 71: 429
  • Jacobs A. Metabolic consequences of iron overload. Br. J. Haematol. 1976; 34: 1
  • Cartei G., Causerano D., Naccarato R. Transferrin behaviour in primary haemochromatosis. Experientia 1975; 31: 373
  • Losowsky M. S. Effects of desferrioxamine in patients with iron-loading with a simple method for estimating urinary iron. J. Clin. Pathol. 1966; 19: 165
  • Balcerzak S. P., Westerman M. P., Heinle E. W., Taylor F. H. Measurement of iron stores using deferoxamine. Ann. Intern. Med. 1968; 68: 518
  • Fielding J., O'Shaughnessy M. C., Brunstrom G. M. Differential ferrioxamine test in idiopathic haemochromatosis and transfusional haemosiderosis. J. Clin. Pathol. 1966; 19: 159
  • Powell L. W., Thomas M. J. Use of diethylenetriamine penta-acetic acid (D.T.P.A.) in the clinical assessment of total body iron stores. J. Clin. Pathol. 1967; 20: 896
  • Harker L. A., Funk D. D., Finch C. A. Evaluation of storage iron by chelates. Am. J. Med. 1968; 45: 105
  • Barry M., Cartei G., Sherlock S. Differential ferrioxamine test in haemochromatosis and liver disease. Gut 1969; 10: 697
  • Smith P. M., Miller J. P. G., Pitcher C. S., Lestas A. N., Dymock I. W., Williams R. The differential ferrioxamine test in the management of idiopathic haemochromatosis. Lancet 1969; 2: 402
  • Barry M., Cartei G., Sherlock S. Quantitative measurement of iron stores with diethylenetriamine penta-acetic acid. Gut 1970; 11: 891
  • Barry M., Cartei G., Sherlock S. Measurement of iron stores in cirrhosis using diethylenetriamine penta-acetic acid. Gut 1970; 11: 899
  • Addison G. M., Beamish M. R., Hales C. N., Hodgkins M., Jacobs A., Llewellin P. An immunoradiometric assay for ferritin in the serum of normal subjects and patients with iron deficiency and iron overload. J. Clin. Pathol. 1972; 25: 326
  • Miles L. E. M., Lipschitz D. A., Bieber C. P., Cook J. D. Measurement of serum ferritin by a 2-site immunoradiometric assay. Anal. Biochem. 1974; 61: 209
  • Halliday J. W., Gera K. L., Powell L. W. Solid phase radioimmunoassay for serum ferritin. Clin. Chim. Acta 1975; 58: 207
  • Jacobs A., Miller F., Worwood M., Beamish M. R., Wardrop C. A. Ferritin in the serum of normal subjects and patients with iron deficiency and iron overload. Br. Med. J. 1972; 4: 206
  • Lipschitz D. A., Cook J. D., Finch C. A. A clinical evaluation of serum ferritin as an index of iron stores. N. Engl. J. Med. 1974; 290: 1213
  • Siimes M. A., Addiego J. E., Dallman P. R. Ferritin in serum: diagnosis of iron deficiency and iron overload in infants and children. Blood 1974; 43: 581
  • Alfrey C. P. Serum ferritin assay. CRC Crit. Rev. Clin. Lab. Sci. 1978; 9: 179
  • Worwood M. Serum ferritin. CRC Crit. Rev. Clin. Lab. Sci. 1979; 10: 171
  • Green R., Watson L. R., Saab G. A., Crosby W. H. “Normal” serum ferritin - a caution. Blood 1977; 50: 545
  • Siimes M. A., Dallman P. R. New kinetic role for serum ferritin in iron metabolism. Br. J. Haematol. 1974; 28: 7
  • Worwood M., Aherne W., Dawkins S., Jacobs A. The characteristics of ferritin from human tissues, serum and blood cells. Clin. Sci. Mol. Med. 1975; 48: 441
  • Arosio P., Yokota M., Drysdale J. W. Characterization of serum ferritin in iron overload: possible identity to natural apoferritin. Br. J. Haematol. 1974; 36: 199
  • Zuyderhoudt F. M. J., Linthorst C., Hengeveld P. On the iron content of human serum ferritin, especially in acute viral hepatitis and iron overload. Clin. Chim. Acta 1978; 90: 93
  • Siimes M. A., Koerper M. A., Licko V., Dallman P. R. Ferritin turnover in plasma: an opportunistic use of blood removed during exchange transfusion. Pediatr. Res. 1975; 9: 127
  • Worwood M., Cragg S. J., Williams A. M., Wagstaff M., Jacobs A. The clearance of 131I-human plasma ferritin in man. Blood 1982; 60: 827
  • Pollock A. S., Lipschitz D. A., Cook J. D. The kinetics of serum ferritin. Proc. Soc. Exp. Biol. Med. 1978; 157: 481
  • Puro D. G., Richter G. W. Ferritin synthesis by free and membrane-bound (poly) ribosomes of rat liver. Proc. Soc. Exp. Biol. Med. 1971; 138: 399
  • Halliday J. W., Mack U., Powell L. W. The kinetics of serum and tissue ferritins: relation to carbohydrate content. Br. J. Haematol. 1979; 42: 535
  • McKeering L. V., Halliday J. W., Caffin J. A., Mack U., Powell L. W. Immunological detection of isoferritins in normal human serum and tissue. Clin. Chim. Acta 1976; 67: 189
  • Aherne W., Worwood M. Some properties of human serum ferritin. Biochem. Soc. Trans. 1974; 2: 429
  • Halliday J. W., McKeering L. V., Tweedale R., Powell L. W. Serum ferritin in haemochromatosis: changes in the isoferritin composition during venesection therapy. Br. J. Haematol. 1977; 36: 395
  • Worwood M., Cragg S. J., Wagstaff M., Jacobs A. Binding of human serum ferritin to concanavalin A. Clin. Sci. 1979; 56: 83
  • Cragg S. J., Wagstaff M., Worwood M. Sialic acid and the microheterogeneity of human serum ferritin. Clin. Sci. 1980; 58: 259
  • Worwood M., Cragg S. J., Jacobs A., McLaren C., Ricketts C., Economidou J. Binding of serum ferritin to concanavalin A: patients with homozygous β thalassaemia and transfusional iron overload. Br. J. Haematol. 1980; 46: 409
  • Prieto J., Barry M., Sherlock S. Serum ferritin in patients with iron overload and with acute and chronic liver diseases. Gastroenterology 1975; 68: 525
  • Walters G. O., Miller F., Worwood M. Serum ferritin concentration and iron stores in normal subjects. J. Clin. Pathol. 1973; 26: 770
  • Letsky E. A., Miller F., Worwood M., Flynn D. M. Serum ferritin in children with thalassaemia regularly transfused. J. Clin. Pathol. 1974; 27: 652
  • Powell L. W., Halliday J. W., Cowlishaw J. L. Relationship between serum ferritin and total body iron stores in idiopathic haemochromatosis. Gut 1978; 19: 538
  • Jacobs A., Worwood M. Ferritin: clinical aspects. Iron Metabolism and its Disorders, H. Kief. Excerpta Medica, Amsterdam 1975; 90
  • Dawkins S., Cavill I., Ricketts C., Worwood M. Variability of serum ferritin concentration in normal subjects. Clin. Lab. Haematol. 1979; 1: 41
  • Valberg L. S., Sorbie J., Ludwig J., Pelletier O. Serum ferritin and the iron status of Canadians. Can. Med. Assoc. J. 1976; 114: 417
  • Mack U., Cooksley W. G. E., Ferris R. A., Powell L. W., Halliday J. W. Regulation of plasma ferritin by the isolated perfused rat liver. Br. J. Haematol. 1981; 47: 403
  • Beaumont C., Simon M., Smith P. M., Worwood M. Hepatic and serum ferritin concentrations in patients with idiopathic hemochromatosis. Gastroenterology 1980; 79: 877
  • Brissot P., Bourel M., Herry D., Verger J. P., Messner M., Beaumont C., Regnouard F., Ferrand B., Simon M. Assessment of liver iron content in 271 patients: a reevaluation of direct and indirect methods. Gastroenterology 1981; 80: 557
  • Roeser H. P., Halliday J. W., Sizemore D. J., Nikles A., Willgoss D. Serum ferritin in ascorbic acid deficiency. Br. J. Haematol. 1980; 45: 457
  • Wands J. R., Rowe J. A., Mezey S. E., Waterbury L. A., Wright J. R., Halliday J. W., Isselbacher K. J., Powell L. W. Normal serum ferritin concentrations in precirrhotic hemochromatosis. N. Engl. J. Med. 1976; 294: 302
  • Halliday J. W., Russo A. M., Cowlishaw J. L., Powell L. W. Serum-ferritin in diagnosis of haemochromatosis. A study of 43 families. Lancet 1977; 2: 621
  • Bassett M. L., Halliday J. W., Powell L. W., Doran T., Bashir H. Early detection of idiopathic haemochromatosis: relative value of serum-ferritin and HLA typing. Lancet 1979; 2: 4
  • Cook J. D., Lipschitz D. A. Clinical measurements of iron absorption. Clin. Haematol. 1977; 6: 567
  • Bezwoda W. R., Bothwell T. H., Torrance J. D., MacPhail A. P., Charlton R. W., Kay G., Levin J. The relationship between marrow iron stores, plasma ferritin concentrations and iron absorption. Scand. J. Haematol. 1979; 22: 113
  • Valberg L. S., Lloyd D. A., Ghent C. N., Flanagan P. R., Sinclair N. R., Stiller C. R., Chamberlain M. J. Clinical and biochemical expression of the genetic abnormality in idiopathic hemochromatosis. Gastroenterology 1980; 79: 884
  • Bomford A., Corrigall A., Walker R. J., Williams R. Iron metabolism in haemochromatosis with reference to a chelatable iron pool and changes in iron absorption. Iron Metabolism and Its Disorders, H. Kief. Excerpta Medica, Amsterdam 1975; 211
  • Olatunbosun D., Corbett W. E. N., Ludwig J., Valberg L. S. Alteration of cobalt absorption in portal cirrhosis and idiopathic hemochromatosis. J. Lab. Clin. Med. 1970; 75: 754
  • Sorbie J., Valberg L. S., Corbett W. E. N., Ludwig J. Serum ferritin, cobalt excretion and body iron status. Can. Med. Assoc. J. 1975; 112: 1173
  • Miller A., Zimelman A., Brauer M. J. A family study of a patient with idiopathic hemochromatosis. Am. J. Hematol. 1977; 2: 41
  • Weinfeld A., Lundin P., Lundvall O. Significance for the diagnosis of iron overload of histo-chemical and chemical iron in the liver of normal subjects. J. Clin. Pathol. 1968; 21: 35
  • Walker R. J., Miller J. P. G., Dymock I. W., Shilkin K. B., Williams R. Relationship of hepatic iron concentration to histochemical grading and to total chelatable body iron in conditions associated with iron overload. Gut 1971; 12: 1011
  • Barry M., Sherlock S. Measurement of liver-iron concentration in needle-biopsy specimens. Lancet 1971; 1: 100
  • Brittenham G. M., Farrell D. E., Harris J. W., Feldman E. S., Danish E. H., Muir W. A., Tripp J. H., Bellon E. M. Magnetic-susceptibility measurement of human iron stores. N. Engl. J. Med. 1982; 307: 1671
  • Mills S. R., Doppman J. L., Nienhuis A. W. Computed tomography in the diagnosis of disorders of excessive iron storage of the liver. J. Comp. Assisted Tomography 1977; 1: 101
  • Houang M. T. W., Arozena X., Skalicka A., Huehns E. R., Shaw D. G. Correlation between computed tomographic values and liver iron content in thalassaemia major with iron overload. Lancet 1979; 1: 1322
  • Chapman R. W. G., Williams G., Bydder G., Dick R., Sherlock S., Kreel L. Computed tomography for determining liver iron content in primary haemochromatosis. Br. Med. J. 1980; 280: 440
  • Blitzer B. L., Weiss G. B., Osbaldiston G. W., Markham R. B., Aamodt R., Berk P. D., Wolff S. M., Fauci A. S. Early idiopathic hemochromatosis with absent stainable bone marrow iron stores. Gastroenterology 1978; 75: 886
  • Cawley E. P., Hsu Y. T., Wood B. T., Weary P. E. Hemochromatosis and the skin. Arch. Dermatol. 1969; 100: 1
  • Chevrant-Breton J., Simon M., Bourel M., Ferrand B. Cutaneous manifestations of idiopathic hemochromatosis. Arch. Dermatol. 1977; 113: 161
  • Zeimer R., Belkin M., Leitersdorff E., Rachmilewitz E. A. A noninvasive method for the evaluation of tissue iron deposition in beta-thalassemia major. J. Lab. Clin. Med. 1978; 91: 24
  • Williams R., Smith P. M., Spicer E. J. F., Barry M., Sherlock S. Venesection therapy in idiopathic haemochromatosis: An analysis of 40 treated and 18 untreated patients. Q. J. Med. 1969; 38: 1
  • Worwood M. Serum ferritin. Iron in Biochemistry and Medicine, A. Jacobs, M. Worwood. Academic Press, New York 1980; Vol. 2: 203
  • Zimelman A. P., Edelstein A., Miller A. Storage iron measurement in hemochromatotic patients reaccumulating iron. Clin. Res. 1977; 25: 352A
  • Bickel H., Gaumann E., Keller-Schierlein W., Prelog V., Vischer E., Wettstein A., Zahner H. Iron-containing growth factors, the sideramines, and their antagonists, the iron-containing sideromycin antibiotics. Experientia 1960; 16: 129
  • Modell C. B., Beck J. Long-term desferrioxamine therapy in thalassemia. Ann. N.Y. Acad. Sci. 1974; 232: 201
  • Barry M., Flynn D. M., Letsky E. A., Risdon R. A. Long-term chelation therapy in thalassaemia major: effect on liver iron concentration, liver histology, and clinical progress. Br. Med. J. 1974; 2: 16
  • Propper R. D., Shurin S. B., Nathan D. G. Reassessment of the use of desferrioxamine B in iron overload. N. Engl. J. Med. 1976; 294: 1421
  • Propper R. D., Cooper B., Rufo R. R., Nienhuis A. W., Anderson W. F., Bunn H. F., Rosenthal A., Nathan D. G. Continuous subcutaneous administration of desferrioxamine in patients with iron overload. N. Engl. J. Med. 1977; 297: 418
  • Hussain M. A. M., Flynn D. M., Green N., Hoffbrand A. V. Effect of dose, time, ascorbate on iron excretion after subcutaneous desferrioxamine. Lancet 1977; 1: 977
  • Pippard M. J., Letsky E. A., Callender S. T., Weatherall D. J. Prevention of iron loading in transfusion-dependent thalassaemia. Lancet 1978; 1: 1178
  • Blume K. G., Beutler E., Chillar R. K., Fahey J. L., Sharkoff D., Zia P. K. Continuous intravenous deferoxamine infusion. Treatment of secondary hemochromatosis in adults. J. Am. Med. Assoc. 1978; 239: 2149
  • Summers M. R., Jacobs A., Tudway D., Perera P., Ricketts C. Studies in desferrioxamine and ferrioxamine metabolism in normal and iron-loaded subjects. Br. J. Haematol. 1979; 42: 547
  • Lipschitz D. A., Dugard J., Simon M. O., Bothwell T. H., Charlton R. W. The site of action of desferrioxamine. Br. J. Haematol. 1971; 20: 395
  • Hershko C., Grady R. W., Cerami C. Mechanism of iron chelation in the hypertransfused rat; definition of two alternate pathways of iron mobilization. J. Lab. Clin. Med. 1978; 92: 144
  • Fairbanks V. F. Chronic iron overload: new chelators and new strategies. J. Lab. Clin. Med. 1978; 92: 141
  • Hoffbrand A. V., Gorman A., Laulicht M., Garidi M., Economidou J., Georgipoulou G., Hussain M. A. M., Flynn D. M. Improvement in iron status and liver function in patients with transfusional iron overload with long-term subcutaneous desferrioxamine. Lancet 1947, 1979
  • Cohen A., Martin M., Schwartz E. Response to long-term deferoxamine therapy in thalassemia. J. Pediatr. 1981; 99: 689
  • Graziano J. H., Piomelli S., Hilgartner M., Giardina P., Karpatkin M., Andrew M., LoIacono N., Seaman C. Chelation therapy in β-thalassemia major. III. The role of splenectomy in achieving iron balance. J. Pediatr. 1981; 99: 695
  • O'Brien R. T. Ascorbic acid enhancement of desferrioxamine-induced urinary iron excretion in thalassemia major. Ann. N.Y. Acad. Sci. 1974; 232: 221
  • Nienhuis A. W., Delea C., Aamodt R., Bartter F., Anderson W. F. Evaluation of desferrioxamine and ascorbic acid for the treatment of chronic iron overload. Birth Defects Original Art. Ser. XII, No. 8, D. Bergsma, A. Cerami, C. M. Peterson. The National Foundation, New York 1976, 1977
  • Graziano J. H., Cerami A. Chelation therapy for the treatment of thalassemia. Semin. Hematol. 1977; 14: 127
  • Hoffbrand A. V. Transfusion siderosis and chelation therapy. Iron in Biochemistry and Medicine, A. Jacobs, M. Worwood. Academic Press, New York 1980; Vol. 2: 499
  • Callender S. T., Weatherall D. J. Iron chelation with oral desferrioxamine. Lancet 1980; 2: 689
  • Jacobs A., Ting W. C. Iron chelation with oral desferrioxamine. Lancet 1980; 2: 794
  • Kattamis C., Fitsialos J., Sinopoulou C. Oral desferrioxamine in young patients with thalassaemia. Lancet 1981; 1: 51
  • Peterson C. M., Graziano J. H., Grady R. W., Jones R. L., Vlassara H. V., Canale V. C., Miller D. R., Cerami A. Chelation studies with 2,3-dihydroxybenzoic acid in patients with β-thalassaemia major. Br. J. Haematol. 1976; 33: 477
  • Graziano J. H., Miller D. R., Grady R. W., Cerami A. Inhibition of membrane peroxidation in thalassaemic erythrocytes by 2,3-dihydroxybenzoic acid. Br. J. Haematol. 1976; 32: 351
  • Muller-Eberhard U., Erlandson M. E., Ginn H. E., Smith C. H. Effect of trisodium calcium diethylenetriaminepentaacetate on bivalent cations in thalassemia major. Blood 1963; 22: 209
  • Grady R. W., Graziano J. H., Akers H., Cerami A. The identification of rhodotorulic acid as a potentially useful iron-chelating drug. Blood 1974; 44: 911
  • Grady R. W., Graziano J. H., Akers H. A., Cerami A. The development of new iron-chelating drugs. J. Pharmacol. Exp. Ther. 1976; 196: 478
  • Grady R. W., Graziano J. H., White G. P., Jacobs A., Cerami A. The development of new iron-chelating drugs. II. J. Pharmacol. Exp. Ther. 1978; 205: 757
  • Pitt C. G., Gupta G., Estes W. E., Rosenkrantz H., Metterville J. J., Crumbliss A. L., Palmer R. A., Nordquest K. W., Sprinkle Hardy K. A., Whitcomb D. R., Byers B. R., Arceneaux J. E. L., Gaines C. G., Sciortino C. V. The selection and evaluation of new chelating agents for the treatment of iron overload. J. Pharmacol. Exp. Ther. 1979; 208: 12
  • Hoy T., Humphrys J., Jacobs A., Williams A., Ponka P. Effective iron chelation following oral administration of an isoniazid-pyridoxal hydrazone. Br. J. Haematol. 1979; 43: 443
  • May P. M., Williams D. R. The inorganic chemistry of iron metabolism. Iron in Biochemistry and Medicine, A. Jacobs, M. Worwood. Academic Press, New York 1980; Vol. 2: 1
  • Pollack S., Ruocco S. Synergistic effect of nitrilotriacetate on iron mobilization by desferrioxamine in vivo. Blood 1981; 57: 1117
  • Young S. P., Baker E., Huehns E. R. Liposome entrapped desferrioxamine and iron transporting ionophores: a new approach to iron chelation therapy. Br. J. Haematol. 1979; 41: 357
  • Lau E. H., Cerny E. A., Rahman Y. E. encapsulated desferrioxamine in experimental iron overload. Br. J. Haematol. 1981; 47: 505
  • Green R., Miller J., Crosby W. Enhancement of iron chelation by desferrioxamine entrapped in red blood cell ghosts. Blood 1981; 57: 866
  • Green R., Lamon J., Curran D. Clinical trial of desferrioxamine entrapped in red cell ghosts. Lancet 1980; 2: 327
  • Piomelli S., Danoff S. J., Becker M. H., Lipera M. J., Travis S. F. Prevention of bone malformations and cardiomegaly in Cooley's anemia by early hypertransfusion regimen. Ann. N.Y. Acad. Sci. 1969; 165: 427
  • Cavill I., Ricketts C., Jacobs A., Letsky E. Erythropoiesis and the effect of transfusion in homozygous β-thalassemia. N. Engl. J. Med. 1978; 278: 776
  • Corash L., Klein H., Deisseroth A., Shafer B., Rosen S., Beman J., Griffith P., Neinhuis A. Selective isolation of young erythrocytes for transfusion support of thalassemia major patients. Blood 1981; 57: 599
  • Graziano J. H., Piomelli S., Seaman C., Wang T., Cohen A. R., Kelleher J. F., Schwartz E. A simple technique for preparation of young red cells for transfusion from ordinary blood units. Blood 1982; 59: 865
  • Monnier L., Colette L., Aguirre L., Mirouze J. Evidence and mechanism for pectin-reduced intestinal inorganic iron absorption in idiopathic hemochromatosis. Am. J. Clin. Nutr. 1980; 33: 1225
  • McLaren G. D., Cragg S. J., Hoy T. G., unpublished data
  • Jacobs A., personal communication
  • Caskey J. H., Jones C., Miller Y. E., Seligman P. A. Human ferritin gene is assigned to chromosome 19. Proc. Natl. Acad. Sci. U.S.A. 1983; 80: 482

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