What Is Hemochromatosis?

Hemochromatosis is a recessive gene disorder in which there is an excessive amount of iron salts in the tissues which damages the tissues in the liver, causes discoloration of the skin and leads to diabetes mellitus. This may cause symptoms such as abdominal pain, weakness and weight loss. Due to excessive amount of iron in the liver, it can lead to heart failure.
Another common disease is Porphyria Cutanea Tarda (PCT) which arises from a lack of the enzyme uroporphyrinogen decarboxylase. Most patients with this disease shows an abnormal level of iron salts in the tissues. The disease becomes active if there is a combination of iron, alcohol, estrogens, HIV and smoking. This may cause a deficiency of the UROD enzyme in the liver. Area that
receives a high level of sunlight exposure such as the face, hands, forearms and lower legs can cause blistering of the skin and be the major symptoms to PCT. PCT is diagnosed by performing laboratory testing.
HFE is a beta2-microglobulin-associated membrane protein. It is a cell surface membrane protein. This protein is involved in iron equilibrium. This will regulate the overload of iron salts in Hemochromatosis disease.
Furthermore, we will be discussing mainly about the disease hemochromatosis and the protein HFE to Poryphyria Cutanea Tarda.

Hemochromatosis
Hemochromatosis is a disease in which an excessive amount of iron is being produced in the body.
If there is too much iron in the body, it can be toxic and be harmful to the organs and cause organ failure. In this disease, iron is mostly accumulated in the pancreas, heart and liver. Hemochromatosis can also be at risk of PCT.
If there is too much iron in the heart, this will cause irregular heartbeats and might lead to heart failure. The irregular heartbeats produced by the heart are called arrhythmias. If there is too much iron in the pancreas, this might lead to diabetes. If the excessive amount of iron in the body is not treated, it can be fatal and thus lead to death.
There are two types of hemochromatosis. They are primary and secondary. Each of them has a different cause. Primary Hemochromatosis has been caused by genes defect. The amount of iron absorbed from food can be controlled from these genes. Secondary Hemochromatosis is usually the result of another disease which cause excessive amount of
iron.
Hemochromatosis can affect different parts of the body which cause various signs and symptoms.
General symptoms such as tiredness can be analysed in women whereas men’ symptoms are more complicated. Weight loss, stomach pain, joint pain and weakness are other common signs and symptoms of this disease.
If the disease is not treated on time, it can cause heart problems, liver disease, joint damage and pain, changes in skin colour, damage of adrenal gland and failure of the reproductive organ.
The disease is diagnosed by an internal medicine specialists. Physical exam is performed to check whether the patient has the signs and symptoms of hemochromatosis. This will be done by listening to the heartbeats of the heart. If the disease is present, the liver will be enlarged, the skin will have an abnormal colour and there will be irregular heartbeats.
Blood tests can be performed to check the level of iron. If Hemochromatosis is present, the level of iron in the body may be high. The doctor may also test for the serum ferritin level. This will show how much iron is being stored in the organ of the body. Another way to diagnose hemochromatosis is to see how much iron is in the patient’s liver. This can be done by magnetic resonance
imaging.
Hemochromatosis is treated in different ways. Treatment can be done by iron chelation therapy, therapeutic phlebotomy or by simply changing diet. If the disease is treated, this will reduce the amount of iron in the patient’s body, thus maintain a normal level of iron and preventing other severe damages to the organs.
Blood and iron is removed from the body by therapeutic phlebotomy. This is done once or twice a week. The iron level of the patient will return to normal after some weeks. Even if it has returned to normal, it has to be performed but less frequent.
If someone has been diagnosed with hemochromatosis, dietary changes can help to reduce iron level in the body. Iron pills, iron injections or any other multivitamins containing iron should be avoided. Moreover, uncooked seafood and shellfish should be avoided as they contain bacteria which can cause infections. Vitamin C should be limited as this absorbs iron from food. The patient should seek a specialist for dietary change.
The accuracy of the mutation in the hemochromatosis phenotype is not precise due to genetic heterogeneity and the lack of the definition in the disease case. The most common mutation is C282Y and H63D alleles of the HFE gene. Even if the mutation has been detected in a patient, there is an incomplete information for the HFE genotype. With the H63D mutation, there is a reduced loss of protein function according to some studies.

HFE gene
The affected gene is HFE gene. In hemochromatosis, both the mother and father must have one copy of the abnormal HFE gene. HFE gene gives some information about the protein being produed. The protein being produced is mainly found on the surface of intestinal cells and some cells in the immune system. The protein helps those cells to regulate the absorption of iron. The mutations in HFE gene can also increase the development of the disease porphyria cutanea tarda also known as PCT.
HFE consists of 7 exons ranging over 12kb. HFE contains 9609 base pairs of DNA on chromosome 6p. This is extended within the HLA class I region. The signal peptide corresponds to exon 1 and exons 2 to 4 correspond to α1, α2, and α3 domains respectively. Exon 5 corresponds to the transmembrane domain. Therefore 6 exons is represented by the full-length transcript.