HFE and non-HFE hemochromatosis.
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 beta2-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.
Anderson
Gregory J
GJ
The Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Australia. gregA@qimr.edu.au
Powell
Lawrie W
LW
D003937:Diagnosis, Differential; D004386:Duodenum / Q000502:physiology; D006432:Hemochromatosis / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism; D008107:Liver Diseases / Q000209:etiology / Q000235:genetics / Q000473:pathology; D008403:Mass Screening; D008565:Membrane Proteins / Q000235:genetics*; D017354:Point Mutation
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D007501:Iron