HFE and Non-HFE Hemochromatosis Authors
Progress in hematology
Received: 31 May 2002 Accepted: 10 June 2002 DOI:
Cite this article as: Anderson, G.J. & Powell, L.W. Int J Hematol (2002) 76: 203. doi:10.1007/BF02982788 Abstract
Hereditary hemochromatosis (HH) is a disorder of iron metabolism in which enhanced absorption of dietary iron causes increased iron accumulation in the liver, heart, and pancreas. Most individuals with HH are homozygous for a point mutation in the
HFE gene, leading to a C282Y substitution in the HFE protein. The function of HFE protein is unknown, but the available evidence suggests that it acts in association with β 2-microglobulin and transferrin receptor 1 to regulate iron uptake from plasma transferrin by the duodenum, the proposed mechanism by which body iron levels are sensed. The identification of HFE has established the foundation for a better understanding of the molecular and cellular biology of iron homeostasis and its altered regulation in HH. Additionally, the ability to accurately diagnose iron overload disorders has been strengthened, family screening has been improved, and evaluation of patients with other forms of liver disease complicated by moderate-to-severe iron overload is now possible. However, the role of HFE testing in generalized population screening for HH is still controversial. Recently, other forms of HH have been described that are not related to HFE but are due to mutations in genes coding iron transport proteins. Key words Iron Iron overload Hemochromatosis Thalassemia HFE IREG1 TfR2 References
Anderson GJ. Ironing out disease: inherited disorders of iron homeostasis.
Bacon BR, Powell LW, Adams PC, et al. Molecular medicine and hemochromatosis: at the crossroads.
. 1999;116: 193–207.
Feder JN, Gnirke A, Thomas W, et al. A novel MHC class I-like gene is mutated in patients with hereditary hemochromatosis.
Guyader D, Jacquelinet C, Moirand R, et al. Noninvasive prediction of fibrosis in C282Y homozygous hemochromatosis.
George DK, Ramm GA,Walker NI, et al. Elevated serum type IV collagen: a sensitive indicator of the presence of cirrhosis in hemochromatosis.
Cullen LM, Anderson GJ, Ramm GA, Jazwinska EC, Powell LW. Genetics of hemochromatosis.
Annu Rev Med.
Anderson GJ,Vulpe CD. Regulation of intestinal iron transport. In: Templeton DM, ed.
Molecular and Cellular Iron Transport. New York: Marcel Dekker; 2002:559–596.
Trinder D, Olynyk JK, Sly WS, Morgan EH. Iron uptake from plasma transferrin by the duodenum is impaired in the HFE knock-out mouse.
Proc Natl Acad Sci.
Tavill AS. Management of hemochromatosis. (AASLD Practice Guidelines)
EASL International Consensus Conference on Hemochromatosis.
Camaschella C, Roetto A, De Gobbi M, et al. Non-HFE hemochromatosis. In: Proceedings from the World Congress on Iron Metabolism. August 18-23, 2001. Cairns, Australia.
Camaschella C, Roetto A, Cali A, et al. The gene TFR2 is mutated in a new type of hemochromatosis mapping to 7q22.
Pietrangelo A, Montosi G, Totaro A, et al. Hereditary hemochromatosis in adults without pathogenic mutations in the hemochromatosis gene.
N Engl J Med.
Montosi G, Donovan A, Totaro A, et al. Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene.
J Clin Invest.
Njajou OT, Vaessen N, Joosse M, et al. A mutation in SLC11A3 is associated with autosomal dominant hemochromatosis.
Wallace DF, Pedersen P, Dixon JL, et al. Novel mutation in ferroportin 1 is associated with autosomal dominant hemochromatosis.
Kato J, Fujikawa K, Kanda M, et al.A mutation, in the iron responsive element of H ferritin mRNA, causing autosomal dominant iron overload.
Am J Hum Genet.
Eason RJ, Adams PC, Aston CE, Searle J. Familial iron overload with possible autosomal dominant inheritance.
Aust NZ J Med. 1990;20:226–230.
Roberts AG, Whatley SD, Morgan RR, et al. Increased frequency of the hemochromatosis Cys282Tyr mutation in sporadic porphyria cutanea tarda.
Stuart KA, Busfield F, Jazwinska EC, et al. The C282Y mutation in hemochromatosis (HFE) gene and hepatitis C virus infection are independent cofactors for porphyria cutanea tarda in Australian patients.
Sampietro M, Piperno A, Lupica L, et al. High prevalence of His63Asp HFE mutation in Italian patients with porphyria cutanea tarda.
Sullivan JL. Iron and the genetics of cardiovascular disease [editorial; comment].
Angelucci E, Brittenham GM, McLaren CE, et al. Hepatic iron concentration and total body iron stores in thalassemia major.
N Engl J Med.
PubMed CrossRef Copyright information
© The Japanese Society of Hematology 2002