Haemochromatosis
Hemochromatosis is defined as a systemic iron overload of genetic origin, caused by reduced concentrations of the iron-regulating hormone ferritin or reduced ferritin-iron transporter protein binding. The most common form of hemochromatosis is due to a pure mutation in HFE (specifically the C282Y mutation), which encodes the hereditary hemochromatosis protein.
Haemochromatosis Subtypes
Type 1: Caused by mutations in HFE.
Type 2A: Caused by mutations in HJV (also known as HFE2).
Type 2B: Caused by mutations in HAMPa.
Type 3: Caused by mutations in TFR2b.
Type 4: Caused by mutations in SLC40A1 that lead to ferroportin gain of activity.
Symptoms of Hemochromatosis
- Prevalent in middle-aged men, rare in women
- The skin is bronze or gray-black, mainly on the face, upper limbs, back of the hands, armpits, and perineum.
- The oral mucosa may have blue-gray or blue-black pigmented spots.
- Because iron is deposited in the liver and pancreas and impairs their functions, there are clinical manifestations of abnormal liver function and diabetes in addition to abnormal skin and mucous membrane pigmentation.
Symptoms of Hemochromatosis [1].
Iron Metabolism Abnormalities in Hemochromatosis
Most of the hereditary hemochromatosis is caused by mutations in the HFE. HFE has two main functions in human iron metabolism, one is to regulate cellular iron uptake and participate in the regulation of intracellular iron homeostasis. The second is to control the expression of small intestinal iron absorption-related proteins, thus participating in the regulation of small intestinal iron absorption. Mutations in HFE, an important molecule in the iron uptake loop, can lead to loss of function of this important iron regulatory mechanism and uncontrolled iron uptake, resulting in excessive iron accumulation in the body.
HFE structure [2].
Ferroptosis Caused by Hemochromatosis
Hemochromatosis is a genetic disorder caused by mutations in genes that impair iron metabolism. Excess iron is absorbed by the intestine and deposited in parenchymal cells, leading to tissue damage and organ failure. In addition to genetic factors, environmental factors such as alcohol consumption and blood loss can affect iron accumulation. Excess iron usually induces ferroptosis by producing large amounts of ROS through the Fenton reaction, which subsequently leads to DNA damage and tissue damage.
Reducing the iron load in the body is the key to the treatment of hereditary hemochromatosis. To find better treatments, this requires an in-depth understanding of the underlying biology of the disease at both the cellular and molecular levels. Protheragen has many years of research experience in the field of iron metabolism research in cells and individuals and is committed to providing the broadest and highest quality tools for hereditary hemochromatosis research. If you are interested in the services we offer, please contact us for more information.
Reference
- Brissot P, et al. Haemochromatosis[J]. Nature Reviews Disease Primers, 2018, 4(1): 1-15.
- Barton J C, et al. HFE gene: Structure, function, mutations, and associated iron abnormalities[J]. Gene, 2015, 574(2): 179-192.