What causes hemochromatosis?

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Hemochromatosis is primarily caused by genetic mutations that lead to excessive absorption of iron from the diet. This excess iron is stored in various organs, particularly the liver, heart, and pancreas, which can lead to serious complications over time. There are different types of hemochromatosis, with the most common being hereditary hemochromatosis.

Causes of Hemochromatosis:

Hereditary Hemochromatosis (Primary Hemochromatosis):
- Genetic Mutation: The most common cause of hereditary hemochromatosis is a mutation in the HFE gene, specifically the C282Y and H63D mutations. The HFE gene normally helps regulate the amount of iron absorbed from food. When it is mutated, the regulation fails, leading to excessive iron absorption.
- Inheritance: Hemochromatosis is inherited in an autosomal recessive manner, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the disease. Individuals with one mutated gene are carriers and typically do not develop the condition, though they may have slightly elevated iron levels.
Secondary Hemochromatosis:
- Blood Disorders: Some blood conditions, such as thalassemia or certain types of anemia, can lead to increased iron absorption and accumulation in the body.
- Chronic Blood Transfusions: Repeated blood transfusions, often necessary for treating certain blood disorders, can lead to iron overload because each transfusion introduces more iron into the body.
- Liver Disease: Chronic liver diseases such as hepatitis or alcoholic liver disease can lead to secondary iron overload.
Juvenile Hemochromatosis:
- Genetic Causes: A rare form of hemochromatosis that occurs in young people, usually caused by mutations in genes other than HFE, such as HJV or HAMP genes. This form often leads to more severe symptoms earlier in life.
Neonatal Hemochromatosis:
- Cause: The exact cause is unclear, but it involves severe iron overload in the fetus, likely due to an immune response during pregnancy rather than a genetic mutation affecting iron metabolism.
Other Rare Forms of Hemochromatosis:
- Mutations in other genes (such as TFR2 or SLC40A1) can also lead to rarer forms of hereditary hemochromatosis, causing abnormal iron accumulation in the body.

Risk Factors:

Family History: Having close relatives with hereditary hemochromatosis increases the risk of developing the condition.
Ethnicity: Hemochromatosis is more common in people of Northern European descent, particularly those of Celtic origin.
Gender: Men are more likely to be diagnosed with hemochromatosis at a younger age because women lose iron through menstruation and pregnancy, which delays the onset of symptoms.

Conclusion:

The primary cause of hemochromatosis is a genetic mutation, usually in the HFE gene, leading to hereditary hemochromatosis. However, other forms of iron overload, such as secondary hemochromatosis, can occur due to chronic medical conditions or treatments. Managing iron levels through early detection and treatment is crucial to preventing complications associated with hemochromatosis, such as liver disease, heart problems, and diabetes.

Ironbound™ A Strategy For The Management Of Hemochromatosis