Anderson Gregory J, Powell Lawrie W
The Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Australia.
Int J Hematol. 2002 Oct;76(3):203-7. doi: 10.1007/BF02982788.
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.
遗传性血色素沉着症（HH）是一种铁代谢紊乱疾病，其中膳食铁吸收增强导致肝脏、心脏和胰腺中铁蓄积增加。大多数HH患者是HFE基因点突变的纯合子，导致HFE蛋白中的C282Y替代。HFE蛋白的功能尚不清楚，但现有证据表明它与β2-微球蛋白和转铁蛋白受体1共同作用，以调节十二指肠从血浆转铁蛋白摄取铁，这是一种推测的机体铁水平感知机制。HFE的鉴定为更好地理解铁稳态的分子和细胞生物学及其在HH中改变的调节奠定了基础。此外，准确诊断铁过载疾病的能力得到了加强，家庭筛查得到了改善，现在也能够对合并中度至重度铁过载的其他形式肝病患者进行评估。然而，HFE检测在HH的一般人群筛查中的作用仍存在争议。最近，已描述了其他形式的HH，它们与HFE无关，而是由于编码铁转运蛋白的基因突变所致。
