An Overview of Hereditary Hemochromatosis

Hereditary hemochromatosis is a genetic disease that causes excess iron to build up in the body. The accumulation of iron in the body may cause a variety of symptoms, such as fatigue, weakness, joint pain, bronze-colored skin, abdominal pain, and sexual problems.

A detailed family history in addition to blood and genetic tests are used to diagnose hemochromatosis. Imaging tests and a liver biopsy may also be used to evaluate for the presence and/or degree of iron accumulation in various organs.

The treatment of hemochromatosis involves the removal of blood (called phlebotomy) in order to lower the body's iron levels.

Cause

Hereditary hemochromatosis is an autosomal recessive genetic disorder and is most common in people with a northern European ancestry.

With hereditary hemochromatosis, a person absorbs too much iron, leading to extra iron being stored in various organs, such as the liver, heart, pancreas, and certain endocrine glands, like the pituitary and thyroid gland.

Symptoms

In the early stages of hereditary hemochromatosis, people usually have no symptoms. Once symptoms develop, they are generally vague and nonspecific (for example, chronic fatigue or weakness). As the disease progresses, symptoms related to iron accumulation within specific organs develop—for example, right-sided abdominal pain from an enlarged liver.

Other potential symptoms and signs of hereditary hemochromatosis include:

• Joint pain and stiffness
• Heart problems (including heart failure and arrhythmia)
• Hypothyroidism
• Diabetes
• Bronze skin discoloration
• Impotence and/or loss of libido in men
• Menstrual irregularities in women
• Loss of bone density (osteoporosis)

Most people do not develop symptoms of hereditary hemochromatosis until they are over 40 when the iron levels have had time to build up in the body. By this stage, the accumulation can impair liver function and increase the risk of liver cancer.

Diagnosis

The diagnosis of hereditary hemochromatosis may come about at different ages, but generally entails a family history, as well as blood and genetic testing.

With children, for instance, a common scenario is that an older close relative is diagnosed with hemochromatosis, and then because it is a genetic disease, other family members undergo testing. So a child might be tested by his pediatrician even before he has any symptoms, just because of his family history.

Alternatively, an adult may get tested because he or she begins developing symptoms of the disease, reports a family history of iron overload, or has evidence of liver disease or abnormal iron laboratory studies.

Blood Tests

The testing for hemochromatosis often begins with a blood test called an iron panel that measures the amount of iron in a person's body.

In a person with hereditary hemochromatosis, the following abnormal blood test results will manifest:

• Elevated transferrin saturation
• Elevated ferritin
• Elevated serum iron
• Decreased total iron-binding capacity (TIBC)

If your iron studies come back as suspicious for iron overload, your healthcare provider will proceed with genetic testing.

Genetic Testing

With genetic testing, your healthcare provider is looking for the defective gene (the HFE gene) that causes hereditary hemochromatosis, including two common gene mutations C282Y (most common) and H63D.

As of now, widespread screening for the C282Y mutation is not recommended as it is not cost-effective. Moreover, the C282Y mutation is common; even if a person has two copies of the mutated HFE gene, most do not develop iron overload.

The American College of Medical Genetics and Genomics recommends genetic testing only for people with a family history of hereditary hemochromatosis or those with evidence of iron overload (a fasting transferrin saturation level over 45%).

Less commonly, healthcare providers may consider testing for people with severe and persistent symptoms (such as fatigue, unexplained cirrhosis, joint pain, heart problems, erectile dysfunction, or diabetes).

Specialist Referral

If a person is found to be homozygous for the mutated HFE gene, they will usually be referred to a healthcare provider who specializes in liver diseases (called a hepatologist or gastroenterologist).

At this point, various tests are often ordered to determine if (and how much) iron overload is present. Some of these tests may include:

• Liver function tests
• Magnetic resonance imaging (MRI) of the liver and heart
• Liver biopsy

Treatment

The main treatment for hemochromatosis is therapeutic phlebotomy, which is a safe, inexpensive, and straightforward therapy.

Phlebotomy

Phlebotomy is a procedure by which a patient has some of their blood (about 500 milliliters) removed once or twice a week for several months to a year, depending on the severity of the iron overload. Once the iron levels have returned to normal, maintenance phlebotomy is usually needed every few months, depending on how quickly iron accumulates within the body.

Lifestyle Strategies

To help prevent iron overload, healthcare providers may advise their patients to avoid iron supplements, as well as vitamin C supplements, which increase the absorption of iron in the gut.

Avoiding the consumption of raw shellfish is also important in people with hemochromatosis because of the risk of infection from bacteria (Vibrio vulnificus) which thrive in iron-rich environments.

Finally, since liver damage is a consequence of hemochromatosis, it's important to moderate alcohol intake, and, if you have liver disease, to avoid alcohol entirely.

A Word From Verywell

If you think you (or your child) are at risk for or may have symptoms of hemochromatosis, please speak to your primary care healthcare provider or a specialist, like a gastroenterologist. Early treatment of hemochromatosis can resolve many symptoms and prevent future complications.