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◉ What is Hemochromatosis?
Hemochromatosis is a hereditary disorder characterized by excessive accumulation of iron in the body. It is a type of iron overload disorder in which the body absorbs and stores more iron than it needs.
The excess iron is deposited in various organs and tissues, particularly the liver, heart, pancreas, and joints. Over time, this excess iron can cause damage and dysfunction in these organs, leading to a variety of complications.
Hemochromatosis is most commonly caused by a mutation in the HFE gene, which regulates the body's absorption of iron. This genetic mutation leads to increased iron absorption from the diet, resulting in abnormally high levels of iron storage.
The most common form of hemochromatosis is called hereditary hemochromatosis, which is inherited in an autosomal recessive manner. This means that an individual needs to inherit two copies of the mutated HFE gene, one from each parent, to develop the disorder. However, there are also other rare forms of hemochromatosis that can be caused by different gene mutations.
◉ Causes
Hemochromatosis is primarily caused by mutations in the HFE gene, which is responsible for regulating the absorption and storage of iron in the body. The most common mutation associated with hereditary hemochromatosis is the C282Y mutation.
In hereditary hemochromatosis, individuals inherit two copies of the mutated HFE gene, one from each parent. This results in increased absorption of iron from the diet and excessive storage of iron in various organs and tissues, particularly the liver.
Other rare forms of hemochromatosis can be caused by mutations in genes other than HFE, such as HAMP (hepcidin), HJV (hemojuvelin), and TFR2 (transferrin receptor 2). These genes play a role in regulating iron metabolism and deficiencies or mutations in these genes can lead to iron overload.
Secondary hemochromatosis can also occur as a result of other conditions or factors that cause increased iron absorption or excessive iron supplementation. These include repeated blood transfusions, certain chronic liver diseases (such as alcoholic liver disease or viral hepatitis), or excessive iron supplementation.
◉ Symptoms and Signs
- Joint pain and stiffness: Excess iron can accumulate in the joints, leading to pain, swelling, and limited range of motion.
- Fatigue and weakness: High iron levels can affect the production of red blood cells, causing fatigue and weakness.
- Abdominal pain: Iron deposition in the liver can lead to hepatomegaly (enlarged liver) or hepatosplenomegaly (enlarged liver and spleen), resulting in abdominal pain.
- Skin pigmentation changes: Excess iron can cause the skin to appear bronze or grayish, particularly in areas exposed to the sun.
- Erectile dysfunction and loss of libido: Hemochromatosis can affect sexual function in men, leading to erectile dysfunction and a decrease in sex drive.
- Heart problems: Iron overload can damage the heart, resulting in cardiomyopathy (enlarged heart) and arrhythmias (abnormal heart rhythms).
- Diabetes: Hemochromatosis can affect the pancreas, leading to insulin resistance and the development of type 2 diabetes.
- Hypothyroidism: Excess iron can impair thyroid function, leading to an underactive thyroid (hypothyroidism).
- Impaired liver function: Iron deposition in the liver can lead to liver damage and liver fibrosis, progressing to cirrhosis in severe cases.
- Increased risk of certain cancers: Hemochromatosis has been associated with an increased risk of liver cancer, pancreatic cancer, and colorectal cancer.
◉ Diagnosis
The diagnosis of hemochromatosis involves a combination of clinical evaluation, family history assessment, and laboratory tests. The following are commonly used diagnostic tools:
• Family history: Hemochromatosis is an inherited disorder, so a family history of the condition is an important clue. If a close relative has been diagnosed with hemochromatosis, it increases the suspicion.
• Physical examination: A healthcare professional may look for signs of hemochromatosis such as skin pigmentation changes, joint pain or swelling, and an enlarged liver or spleen.
• Blood tests: Several laboratory tests can help diagnose hemochromatosis, including:
- Serum iron levels: Increased levels of iron in the blood may indicate hemochromatosis.
- Transferrin saturation: The percentage of iron bound to transferrin in the blood. Elevated levels suggest hemochromatosis.
- Serum ferritin: Increased ferritin levels are often seen in hemochromatosis. Ferritin is a protein that stores iron.
- Liver function tests: Assessing liver enzyme levels and other liver function markers can help evaluate the extent of liver damage.
• Genetic testing: Genetic testing can confirm the presence of specific mutations in the HFE gene, which are associated with the majority of cases of hereditary hemochromatosis.
- The most common HFE gene mutation tested for is C282Y.
- If a person has two copies of the C282Y mutation or one copy of C282Y and another mutation called H63D, it is highly suggestive of hereditary hemochromatosis.
• Imaging studies: In certain cases, imaging studies such as ultrasound or MRI may be performed to assess iron accumulation in the liver and other organs.
◉ Treatment
The treatment of hemochromatosis aims to reduce the iron overload in the body and manage the associated complications. The main treatment options include:
- Phlebotomy: The primary treatment for hemochromatosis is the regular removal of blood (phlebotomy). The frequency and volume of phlebotomy sessions will depend on the individual's iron levels and response to treatment. Initially, phlebotomy may be done weekly or biweekly until iron levels normalize, and then it may be done less frequently to maintain iron balance. Phlebotomy effectively reduces iron stores by removing excess iron-rich red blood cells.
- Iron chelation therapy: In cases where phlebotomy is not possible or insufficient, iron chelation therapy may be considered. This involves the use of medications that bind to iron and facilitate its elimination from the body. Iron chelators, such as deferasirox or deferoxamine, may be prescribed to help reduce iron levels.
- Dietary modifications: Individuals with hemochromatosis are advised to avoid foods that are high in iron, such as red meat and iron-fortified foods. Vitamin C-rich foods or supplements that enhance iron absorption should also be limited. It is recommended to have a well-balanced diet with a focus on avoiding excessive iron intake.
- Monitoring and follow-up: Regular monitoring of iron levels, liver function, and other organ functions is important to assess response to treatment and detect any complications. Individuals with hemochromatosis should have regular check-ups with their healthcare provider, including blood tests and imaging studies when necessary.
- Management of complications: Hemochromatosis can lead to various complications, including liver disease, diabetes, and heart problems. Treatment of these complications may involve medications, lifestyle modifications, and appropriate interventions such as liver transplantation in severe cases.
