Hemochromatosis (Iron Overload): What to Know

Hemochromatosis is a medical condition where people have excessive iron in the body. The most common cause is an inherited genetic change, but blood transfusions and liver disease can also lead to hemochromatosis. Symptoms can be subtle, including fatigue, joint pain, and rusty or greyish appearing skin color.

Untreated hemochromatosis can cause medical complications, such as liver damage or heart failure. Treatment involves removing excess iron from the body through therapeutic phlebotomy (removing red blood cells), which usually results in a good outcome.

This article describes the types, causes, effects, and treatment of hemochromatosis.

Types and Causes of Hemochromatosis

Hemochromatosis is generally categorized as primary or secondary. Primary hemochromatosis is inherited and caused by gene alterations that affect the way the body absorbs iron. Secondary hemochromatosis occurs due to underlying diseases that cause excessive iron buildup.

Primary Hemochromatosis: A Genetic Mutation

Primary hemochromatosis occurs due to an alteration of normal iron absorption, usually caused by an inherited genetic mutation. With primary hemochromatosis, you absorb excessive amounts of iron from your food, and the iron builds up in the body—causing the symptoms and effects of hemochromatosis.

Inherited hemochromatosis is caused by a mutation in the hereditary Fe gene (Fe is the chemical symbol for iron), referred to as the HFE gene. The most common mutations that can cause hemochromatosis are C282Y and H63D, which are both located on the HFE gene.

The inheritance pattern of primary care hemochromatosis is autosomal recessive, which means that the condition causes symptoms if you inherit the gene mutation from both parents. You should not have symptoms if you inherit only one copy of the mutation.

If a person is a carrier of the mutation, they would not have symptoms, but their offspring could inherit the condition if the other parent also has the gene. Symptoms for this type of hemochromatosis usually begin during your 40s or 50s.

Secondary Hemochromatosis: The Result of a Condition

Secondary hemochromatosis occurs due to medical conditions or circumstances that lead to iron overload in the body.

Causes of secondary hemochromatosis include:

• Frequent blood transfusions (usually as treatment for a blood disorder)
• Kidney failure
• Liver disease

Excess iron supplements or excess dietary iron is a rare cause of hemochromatosis—even with high iron intake, the body’s absorption and elimination of iron might remain near normal.

Juvenile Hemochromatosis

Juvenile hemochromatosis starts to have effects before age 30. It can cause delayed puberty, heart disease, diabetes, joint pain, and liver disease. This condition is caused by the inheritance of abnormal variations of HAMP or HJV genes, and it is inherited in an autosomal recessive pattern.

Neonatal Hemochromatosis

Neonatal hemochromatosis is a rare disorder that affects newborns. It is caused by damage to the infant’s liver that might result from the birthing parent’s immune system. The liver damage causes excess iron accumulation in the baby’s body.

Risk Factors for Hemochromatosis

The most significant risk factor for developing hemochromatosis is having a parent who carries the genetic mutation. You could also be at risk of developing secondary hemochromatosis if you have an underlying cause of iron overload.

You might already know that you are at risk of hereditary hemochromatosis if one of your parents, a sibling, or another blood relative has the condition. In this situation, you might want to get tested to see if you have inherited the mutation. If you plan to have children, you and your partner may want to get tested to determine the potential risk to your offspring.

Secondary hemochromatosis risk factors include blood disorders treated with repeated blood transfusions, such as sickle cell disease or thalassemia. Additionally, you could be at risk if you have liver disease, kidney disease, or if you take high doses of iron supplements.

Hemochromatosis Symptoms 

Early detection and treatment are important because complications of hemochromatosis can be serious—and many of the complications can’t be reversed after they develop.

Signs and symptoms of hemochromatosis include:

• Fatigue
• Brain fog (feeling mentally drained and unable to concentrate)
• Mood swings
• Weight loss
• Joint pain
• Weakness
  
• Signs of liver disease—enlarged abdomen, darkening or grey-looking skin
• Diabetes due to damage to the pancreas
• Heart abnormalities—irregular heart rhythms or heart failure
• Pituitary damage can cause menstrual irregularities or sexual dysfunction
• Damage to the adrenal gland can cause blood pressure abnormalities
• Damage to the thyroid gland can cause hypothyroidism (reduced thyroid hormone)

These signs and symptoms may worsen gradually with hemochromatosis. It’s important to get medical attention for these symptoms, whether you are at risk of hemochromatosis or not. 

How Hemochromatosis Is Diagnosed

The diagnosis of hereditary hemochromatosis can include genetic testing and measurements of iron levels. If you have risk factors for secondary hemochromatosis, you might have periodic monitoring of your iron levels so this problem can be detected and treated as soon as your iron levels build up—this can help prevent symptoms and complications from developing.

Check Your Family History

Your family history is an important aspect of getting diagnosed with hereditary hemochromatosis. If you have a known family history of this condition, you can get a diagnosis before symptoms develop. You might want to get tested to know the risk to your offspring.

Since the hereditary type of hemochromatosis is autosomal recessive, you might have relatives who are carriers and don't have the disease—and therefore, you might not know that you have a family history. In these situations, it might take longer for you to get a diagnosis, as the symptoms are not specific to hemochromatosis.

Physical Exam 

In the early stages, hemochromatosis might not cause signs that are easily detected with a physical examination. Some signs of hemochromatosis can be associated with the complications.

Physical exam signs may include:

• Skin discoloration
• Enlarged liver
• Joint tenderness
• Irregular heart rate
• Weight loss

Blood Tests

A few different types of blood tests can help in the diagnosis of hemochromatosis:

• Genetic testing: A blood test can be used to identify the mutations that cause hereditary hemochromatosis. 
• Iron: Ferritin is a protein that increases with higher iron storage. Ferritin levels above 300 nanograms per milliliter (ng/mL) in males or above 200 ng/mL in females can support a diagnosis of hemochromatosis. Other conditions can increase this protein level, and a high level is not diagnostic of hemochromatosis.
• Transferrin: Transferrin is a protein that binds and transports iron. The transferrin saturation (TSAT) measures the percent of iron bound to transferrin, and it increases with higher iron levels. A TSAT higher than 45% could indicate hemochromatosis.

Liver Biopsy

A liver biopsy is a procedure that involves removing a small sample of liver tissue. This tissue can be examined and may detect abnormal iron accumulation in the liver.

MRI

Magnetic resonance imaging (MRI) is an imaging test that can be used to detect and measure the accumulation of iron in the liver.

Hemochromatosis Treatment 

If you have hereditary hemochromatosis, you will need lifelong treatment and monitoring. Treatment can help lower iron in the body and prevent complications.

With secondary hemochromatosis, you will need treatment to remove excess iron. You may need management of your underlying cause and ongoing surveillance to identify any recurrence of iron overload.

The treatment of most types of hemochromatosis typically involves therapeutic phlebotomy, which involves removing blood. This therapy usually lowers iron stores in the body, but the effect is temporary.

Red blood cells contain the iron-containing protein hemoglobin, which carries oxygen and carbon dioxide. Your body will use excess iron stores to make new red blood cells.

But, in hereditary hemochromatosis, you continue absorbing and storing excess iron so that it may rise to excessive levels again. Therefore, you might need an ongoing surveillance and treatment schedule.

In some cases, chelation therapy, a medication that binds to iron, can be used to remove iron accumulation. Medications used for chelation include deferoxamine, deferasirox, or deferiprone. This can be an option if you have a low red blood cell count—which could become even lower if you have treatment with phlebotomy.

Initial Treatment

Your initial treatment may include weekly monitoring and therapeutic phlebotomy, with close monitoring of your red blood cell levels and your iron levels. Once you have reached a safe level, you will be ready for maintenance treatment.

Maintenance Treatment

For ongoing management of hemochromatosis, you may need periodic surveillance of your iron levels and therapeutic phlebotomy. Depending on the severity of your condition, you may have these tests and treatments every few months.

Complications of Hemochromatosis

The complications of hemochromatosis are associated with organ damage and can develop over time.

Complications may include:

• A risk of infections due to bacteria that thrive in iron-rich environments
• Thyroid gland damage, which can cause hypothyroidism
• Liver damage, which may result in liver failure, cirrhosis, or liver cancer
• Diabetes due to pancreatic damage
• Arthritis and joint damage
• Heart failure

All of these issues can cause severe health problems, with symptoms that may include shortness of breath, malnutrition, chronic pain, and may even lead to death.

Hemochromatosis Home Remedies

While lifestyle strategies cannot cure hemochromatosis or improve very high iron levels, lifestyle adjustments can help manage iron levels.

The Centers for Disease Control and Prevention (CDC) recommends the following strategies for living with hemochromatosis:   

• Avoid vitamin C supplements and iron supplements, which can increase iron throughout
  your body.
• Avoid alcohol because alcohol increases the risk of liver damage.
• Prevent infections by not eating uncooked fish and shellfish and getting recommended vaccinations.

Summary 

Hemochromatosis is a buildup of iron in the body. There are hereditary forms of this condition. The more common hereditary forms begin to cause symptoms during adulthood, during the 40s and 50s, while a less common hereditary form begins to cause symptoms during the teen years. A rare infantile form is caused by maternal antibodies (immune proteins) that damage the newborn liver.

Secondary hemochromatosis is iron buildup due to medical risks, which include repeated blood transfusions or liver disease. Complications of untreated hemochromatosis include damage to the liver, heart, thyroid gland, joints, and pancreas.

Iron accumulation is usually effectively treated with therapeutic phlebotomy (red blood cell removal), which can help prevent complications. Management of hereditary hemochromatosis requires lifetime surveillance and therapy. Management of secondary hemochromatosis involves treatment of the underlying condition and ongoing monitoring and therapy.