Hemochromatosis type 4 (also called ferroportin disease) is a disease in which too much iron builds up in the body. This is also called iron overload. Accumulation of iron in the organs is toxic and can cause organ damage. While many organs can be affected, iron overload is especially likely to affect the liver, heart, and pancreas. Hemochromatosis type 4 can be further divided into two subtypes:

• Hemochromatosis type 4A
• Hemochromatosis type 4B

People with hemochromatosis type 4A might not have any symptoms of the disease. Other individuals may develop liver disease as they get older. Hemochromatosis type 4B can be associated with fatigue, weakness, and joint pain. Other symptoms may include abdominal pain, loss of sex drive, liver disease, diabetes, heart problems, difficulty breathing, and skin discoloration. Symptoms of hemochromatosis type 4B can begin anytime from childhood to adulthood. Hemochromatosis type 4 is most common in people of southern European ancestry.

Hemochromatosis type 4 is caused by genetic changes (mutations or pathogenic variants) to the SLC40A1 gene. The disease is inherited in an autosomal dominant manner. A diagnosis of hemochromatosis type 4 is suspected when a doctor observes signs and symptoms of the disease. A doctor may decide to order laboratory tests including a liver biopsy, MRI, or blood test. The diagnosis can be confirmed with genetic testing. Treatment of hemochromatosis type 4B usually involves reducing iron levels by removing blood (phlebotomy) or iron chelation. These treatments can prevent additional organ damage but typically do not reverse existing damage. People with hemochromatosis type 4A may not be recommended to have phlebotomy because it can increase the risk for complications such as anemia.

Hemochromatosis type 4 is inherited in an autosomal dominant manner. This means that people with hemochromatosis type 4 have a genetic change (mutation or pathogenic variant) in one copy of the SLC40A1 gene in each cell of the body. We inherit one copy of every gene from our mother and the other from our father. In most cases, a person who has hemochromatosis type 4 inherited the pathogenic variant causing the disease from one of his or her parents.

When a person with hemochromatosis type 4 has children, each child has a:

• 50% chance to inherit the pathogenic variant in the SLC40A1 gene
• 50% chance to inherit the working copy of SLC40A1, meaning he or she will not develop symptoms of hemochromatosis type 4

Hemochromatosis type 4 is a disease that shows reduced penetrance. This means that some people with pathogenic variants in the SLC40A1 gene never show symptoms of the disease. However, children or other family members who have pathogenic variants causing hemochromatosis type 4 may show symptoms of the disease.

Your doctor will diagnose hemochromatosis based on your medical and family histories, a physical exam, and the results from tests and procedures.

The disease sometimes is detected while checking for other diseases or conditions, such as arthritis, liver disease, diabetes, heart disease, or erectile dysfunction (impotence).

Specialists Involved

Family doctors and internal medicine specialists may diagnose and treat hemochromatosis. Other doctors also may be involved in diagnosing and treating the disease, including:

• Hematologists (blood disease specialists)
• Cardiologists (heart specialists)
• Endocrinologists (gland system specialists)
• Hepatologists (liver specialists)
• Gastroenterologists (digestive tract specialists)
• Rheumatologists (specialists in diseases of the joints and tissues)

Medical and Family Histories

To learn about your medical and family histories, your doctor may ask:

• About your signs and symptoms, including when they started and their severity.
• Whether you take iron (pills or injections) with or without vitamin C supplements (vitamin C helps your body absorb iron from food). If so, your doctor may ask how much iron you take. This information can help him or her diagnose secondary hemochromatosis.
• Whether other members of your family have hemochromatosis.
• Whether other members of your family have a history of medical problems or diseases related to hemochromatosis.

Physical Exam

Your doctor will do a physical exam to check for signs and symptoms of hemochromatosis. He or she will listen to your heart for irregular heartbeats and check for arthritis, abnormal skin color, and an enlarged liver.

Diagnostic Tests and Procedures

Your doctor may recommend one or more tests or procedures to diagnose hemochromatosis.

Blood Tests

In hemochromatosis, the amount of iron in your body may be too high, even though the level of iron in your blood is normal. Certain blood tests can help your doctor find out how much iron is in your body.

During these tests, a sample of blood is taken from your body. It's usually drawn from a vein in your arm using a needle. The procedure usually is quick and easy, although it may cause some short-term discomfort.

The blood tests you have may include transferrin saturation (TS), serum ferritin level, and liver function tests.

Transferrin is a protein that carries iron in the blood. The TS test shows how much iron the transferrin is carrying. This helps your doctor find out how much iron is in your body.

Your doctor may test your serum ferritin level if your TS level is high. A serum ferritin level test shows how much iron is stored in your body's organs. A buildup of iron may suggest hemochromatosis.

You may have liver function tests to check for damage to your liver. Liver damage may be a sign of hemochromatosis. If you have hemochromatosis, liver function tests may show the severity of the disease.

Blood tests alone can't diagnose hemochromatosis. Thus, your doctor may recommend other tests as well.

Liver Biopsy

During a liver biopsy, your doctor numbs an area near your liver and then removes a small sample of liver tissue using a needle. The tissue is then looked at under a microscope.

A liver biopsy can show how much iron is in your liver. This procedure also can help your doctor diagnose liver damage (for example, scarring and cancer). Liver biopsies are less common now than in the past.

Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) is a safe test that uses radio waves, magnets, and a computer to create pictures of your organs. An MRI may be done to show the amount of iron in your liver.

Superconducting Quantum Interference Device

A superconducting quantum interference device (SQuID) is a machine that uses very sensitive magnets to measure the amount of iron in your liver. This machine is available at only a few medical centers.

Genetic Testing

Genetic testing can show whether you have a faulty HFE gene or genes. However, even if you do have two faulty HFE genes, the genetic test can't predict whether you'll develop signs and symptoms of hemochromatosis.

Also, genetic testing may not detect other, less common faulty genes that also can cause hemochromatosis.

There are two ways to do genetic testing. Cells can be collected from inside your mouth using a cotton swab, or a sample of blood can be drawn from a vein in your arm.

People who have hemochromatosis (or a family history of it) and are planning to have children may want to consider genetic testing and counseling. Testing will help show whether one or both parents have faulty HFE genes. A genetic counselor also can help figure out the likelihood of the parents passing the faulty genes on to their children.

Treatment for hemochromatosis type 4 depends on whether the affected person has hemochromatosis type 4A or hemochromatosis type 4B. People with hemochromatosis type 4B can be treated similarly to people who have other types of hemochromatosis. Treatment options may include reducing iron levels by removing blood (phlebotomy), iron chelation therapy, dietary changes, and treatment for complications of the disease.

Treatment for people with hemochromatosis type 4A typically does not involve phlebotomy. This is because people with hemochromatosis type 4A may develop low levels of red blood cells (anemia) if they receive phlebotomy treatments. Instead, people with hemochromatosis type 4A are closely monitored with blood tests to determine if they are having symptoms of the disease and how the disease may best be treated.

Dietary recommendations for people with hemochromatosis may include avoiding alcohol and red meat. People with hemochromatosis are not recommended to take iron or vitamin C supplements.