Hemochromatosis is caused by a defect in a gene called HFE, which was directly linked to the condition in 1996. HFE regulates the amount of iron the body absorbs from food. The body contains approximately 30,000 genes, which are passed from parents to children. There are two known mutations of HFE, called C282Y and H63D.

Patients who inherit the C282Y mutation from both parents may develop hemochromatosis. However, it is not known how many people who inherit two C282Y mutations will eventually develop the condition. Also, it is not known why some people with the genes develop hemochromatosis and others do not. It is highly probable that genes other than HFE play a role in familial iron overload in other populations.

In rare cases, patients who inherit the C282Y mutation from one parent and the H63D mutation from another may develop hemochromatosis. Patients who inherit only one mutation from a parent are carriers of hemochromatosis, which means that they could potentially pass the condition on to their offspring, but rarely develop the condition themselves.

The defective genes that cause hemochromatosis are normally present at birth, although patients rarely develop symptoms until adulthood. The causes of juvenile hemochromatosis and neonatal hemochromatosis (two forms of the condition in which patients develop symptoms at a younger age) are unknown.

Risk factors for developing hemochromatosis include:

• Family history. People with a close relative that has hemochromatosis, such as a parent or sibling, face a greater risk of developing the condition.
  
  
• Ethnicity. People of Northern European descent (e.g., Scottish, British, Dutch, German, Irish and French) develop hemochromatosis more often than others. The condition is less common in African Americans, Hispanic Americans, Asian Americans and Native Americans.
  
  
• Gender. Men are five times more likely to develop hemochromatosis than women.