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Patients with biochemical iron overload: causes and characteristics of a cohort of 150 cases

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Abstract

Biochemical iron overload (IO) is a frequent metabolic abnormality. It may be caused by several diseases, and data regarding the relative frequency of these are scant. A single diagnostic protocol including clinical, biochemical, and genetic data was used to diagnose the cause of biochemical IO in a group of 150 patients referred by general practitioners. Severe alterations of the HFE gene (42 patients, 28%), hepatitis C virus infection (33 patients, 22%), and dysmetabolic syndrome with iron overload (DSIO) (22 patients, 15%) emerged as the main causes, and other single causes were found in 20 patients (13%). In 19 patients (13%), multiple causes of IO were found, and in 14 patients no cause was found, 5 of whom had classical criteria of genetic hemochromatosis (GH) without HFE mutations. Transferrin saturation index (TSI) had a very low positive predictive value (0.16) for GH among patients with biochemical IO in this setting. In conclusion, 90% of patients with biochemical IO were diagnosed with a specific disorder. GH, hepatitis C infection, and DSIO were the major causes, and a large group of patients had multiple causes of IO. TSI is not a useful indicator of GH in patients referred by general practitioners.

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References

  1. Altes A, Gimferrer E, Capella G, Barcelo MJ, Baiget M (1999) Colorectal cancer and HFE gene mutations. Haematologica 84:479–480

    CAS  PubMed  Google Scholar 

  2. Altes A, Souto JC, Mateo J, Borrell M, Fontcuberta J (1997) Activated protein C resistance assay when applied in the general population. Am J Obstet Gynecol 176:358–359

    Article  CAS  PubMed  Google Scholar 

  3. Bacon BR, Powell LW, Adams PC, Kresina TF, Hoofnagle JH (1999) Molecular medicine and hemochromatosis: at the crossroads. Gastroenterology 116:193–207

    Article  CAS  PubMed  Google Scholar 

  4. Baiget M, Barcelo MJ, Gimferrer E (1998) Frequency of the HFE C282Y and H63D mutation in distinct ethnic groups living in Spain. J Med Gen 35:701

    Article  CAS  Google Scholar 

  5. Beard J (2001) Iron status of free-living elderly individuals Am J Clin Nutr 73:503–504

    CAS  PubMed  Google Scholar 

  6. Bonkovsky HL, Jawaid Q, Tortorelli K, LeClair P, Cobb J, Lambrecht RW, Banner BF (1999) Non-alcoholic steatohepatitis and iron: increased prevalence of mutations of the HFE gene in non-alcoholic steatohepatitis. J Heptatol 31:421–429

    Article  CAS  Google Scholar 

  7. Bonkovsky HL, Ponka P, Bacon BR, Drysdale J, Grace ND, Tavill AS (1996) An update on iron metabolism: summary of the fifth international conference on disorders of iron metabolism. Hepatology 24:718–729

    Article  CAS  PubMed  Google Scholar 

  8. Dadone MM, Kushner JP, Edwards CQ, Bishop DT, Skolnick MH (1982) Hereditary hemochromatosis. Analysis of the laboratory expression of the disease by genotype in 18 pedigrees. Am J Clin Pathol 78:196–207

    Article  CAS  PubMed  Google Scholar 

  9. EASL International Consensus Conference on Haemochromatosis (2000) J Hepatol 33:485–504

    Article  Google Scholar 

  10. Fargion S, Mattioli M, Francanzani AL, Sampietro M, Tavazzi D, Fociani P, Taioli E, Valenti L, Fiorelli G (2001) Hyperferritinemia, iron overload, and multiple metabolic alterations identify patients at risk for nonalcoholic steatohepatitis. Am J Gastroenterol 96:2448–2455

    Article  CAS  PubMed  Google Scholar 

  11. Farinati F, Carin R, De Maria N, Della Libera G, Marafin C, Lecis E, Burra P, Floreani A, Cecchetto A, Naccarato R (1995) Iron storage, lipid peroxidation and glutathione turnover in chronic anti-HCV positive hepatitis. J Hepatol 22:449–456

    Article  CAS  PubMed  Google Scholar 

  12. Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA, Basava A, Dormishian F, Domingo R Jr, Ellis MC, Fullan A, Hinton LM, Jones NL, Kimmel BE, Kronmal GS, Lauer P, Lee VK, Loeb DB, Mapa FA, McClelland E, Meyer NC, Mintier GA, Moeller N, Moore T, Morikang E, Wolff RK (1996) A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 13:399–408

    Article  CAS  PubMed  Google Scholar 

  13. Fleming DJ, Jacques PF, Tucker KL, Massaro JM, D'Agostino RB SR, Wilson PW, Wood RJ (2001) Iron status of the free-living, elderly Framingham Heart Study cohort: an iron-replete population with a high prevalence of elevated iron stores. Am J Clin Nutr 73:638–646

    CAS  PubMed  Google Scholar 

  14. Gandon Y, Guyader D, Heautot JF, Reda MI, Yaouanq J, Buhe T, Brissot P, Carsin M, Deugnier Y (1994) Hemochromatosis: diagnosis and quantification of liver iron with gradient-echo MR imaging. Radiology 193:533–538

    Article  CAS  PubMed  Google Scholar 

  15. George DK, Goldwurm S, Macdonald GA, Cowley LL, Walker NI, Ward PJ, Jazwinska EC, Powell LW (1998) Increased hepatic iron concentration in nonalcoholic steatohepatitis is associated with increased fibrosis. Gastroenterology 114:311–318

    Article  CAS  PubMed  Google Scholar 

  16. Gochee PA, Powell LW, Cullen DJ, Du Sart D, Rossi E, Olynyk JK (2002) A population-based study of the biochemical and clinical expression of the H63D hemochromatosis mutation. Gastroenterology122:646–651

  17. Hezode Ch, Cazeneuve C, Coue O, Roudot-Thoraval F, Lonjon I, Bastie A, Duvoux C, Pawlotsky JM, Zafrani ES, Amselem S, Dhumeaux D (1999) Liver iron accumulation in patients with chronic active hepatitis C: prevalence and role of hemochromatosis gene mutations and relationship with hepatic histological lesions. J Hepatol 31:979–984

    Article  CAS  PubMed  Google Scholar 

  18. Kazemi-Shirazi L, Datz Ch, Maier-Dobersberger T, Kaserer K, Hackl F, Polli C, Steindl PE, Penner E, Ferenci P (1999) The relation of iron status and hemochromatosis gene mutations in patients with chronic hepatitis C. Gastroenterology 116:127–134

    Article  CAS  PubMed  Google Scholar 

  19. Leggett BA, Halliday JW, Brown NN, Bryant S, Powell LW (1990) Prevalence of haemochromatosis amongst asymptomatic Australians. Br J Haematol 74:525–530

    Article  CAS  PubMed  Google Scholar 

  20. Mendler M, Turlin B, Moirand R, Jouanolle AM, Sapey T, Guyader D, Le Gall JY, Brissot P, David V, Deugnier Y (1999) Insulin resistance-associated hepatic iron overload. Gastroenterology 117:1155–1163

    Article  CAS  PubMed  Google Scholar 

  21. Moirand R, Mortaji AM, Loreal O, Paillard F, Brissot P, Deugnier Y (1997) A new syndrome of liver iron overload with normal transferrin saturation. Lancet 349:95–97

    Article  CAS  PubMed  Google Scholar 

  22. Nielsen P, Günther U, Dürken M, Fischer R, Düllmann (2000) Serum ferritin iron in iron overload and liver damage: correlation to body iron stores and diagnostic relevance. J Lab Clin Med 135:413–418

    Article  CAS  PubMed  Google Scholar 

  23. Porter JB (2001) Practical management of iron overload Br J Haematol 115:239–252

    Article  CAS  PubMed  Google Scholar 

  24. Remacha AF, Carrasco M, Sarda MP, Barcelo MJ, Baiget M (1999) HFE mutation analysis in patients with hepatitis C virus with positive screening for iron overload. Haematologica 84:284–285

    CAS  PubMed  Google Scholar 

  25. Remacha AF, Carrasco M, Sarda MP, Barceló MJ, Blesa I, Baiget M (2000) Screening for iron overload and HFE mutations in a university hospital. Haematologica 85:873–874

    CAS  PubMed  Google Scholar 

  26. Smith BC, Grove J, Guzail MA, Day CP, Daly AK, Burt AD, Bassendine MF (1998) Heterozygosity for hereditary hemochromatosis is associated with more fibrosis in chronic hepatitis C. Hepatology 27:1695–1699

    Article  CAS  PubMed  Google Scholar 

  27. Thorburn D, Curry G, Spooner R, Spence E, Oien K, Halls D, Fiox R, McCruden EA, McSween RN, Mills PR (2002) The role of iron and haemochromatosis gene mutations in the progression of liver disease in chronic hepatitis C. Gut 50:248–252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Hematology Department, Hospital de la Santa Creu i Sant Pau. Autonomous University of Barcelona, Sant Antoni Mª Claret 167, 08025 , Barcelona, Spain

    A. Altes, A. F. Remacha, A. Sureda, R. Martino, J. Briones, S. Brunet & J. Sierra

  2. Genetic Service. Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Spain

    M. Baiget

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  1. A. Altes
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  2. A. F. Remacha
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  3. A. Sureda
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  4. R. Martino
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  5. J. Briones
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  7. M. Baiget
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  8. J. Sierra
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Correspondence to A. Altes.

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Altes, A., Remacha, A.F., Sureda, A. et al. Patients with biochemical iron overload: causes and characteristics of a cohort of 150 cases. Ann Hematol 82, 127–130 (2003). https://doi.org/10.1007/s00277-002-0595-8

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  • DOI: https://doi.org/10.1007/s00277-002-0595-8

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