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Hemochromatosis

Hemochromatosis a multi-organ disorder that results from excess iron deposition in the liver, pancreas, heart, thyroid, joints, skin, gonads, and pituitary (Porter 2021). Under normal circumstances, dietary iron is absorbed by the small intestine, transported in the blood, bound to the plasma protein transferrin, and delivered to the liver, the major site of iron storage.

When excess iron exceeds transferrin transport capacity, unbound (free) iron circulates and is readily taken up by hepatic, endocrine, and cardiac parenchymal cells. The excess free iron accumulates and catalyzes the production of free radicals inside the cell of the affected tissues. The free radicals promote inflammation, cell injury, and death. To summarize, free iron damages of cells through increased oxidative stress, resulting in an increase in the production of fibrotic tissue.

Etiology

Primary hemochromatosis is a common autosomal recessive disorder caused by a defect in the genes that control how much iron is absorb from food. The genes usually involved in primary hemochromatosis are called HFE genes. Faulty HFE genes cause the body to absorb too much iron.

If you inherit two copies of the faulty HFE gene (one from each parent), you're at risk for iron overload and signs and symptoms of hemochromatosis
If you inherit one faulty HFE gene and one normal HFE gene, you're a hemochromatosis "carrier." Carriers usually don't develop the disease. However, they can pass the faulty gene on to their children. Estimates suggest that about 1 in 10 people in the United States are hemochromatosis carriers.
If two parents are carriers of the faulty HFE gene, then each of their children has a 1 in 4 chance of inheriting two faulty HFE genes.
Although less common, other faulty genes also can cause hemochromatosis. Researchers continue to study what changes to normal genes may cause the disease

There are 4 types of primary hemochromatosis:

Type 1 results from a mutation in the HFE gene. It is one of the most common genetic disorders in the United States, affecting about 1 million people of Northern European descent.

Type 2 results from mutations in either the HJV or HAMP gene.

Type 3 results from mutations in the TFR2 gene

Type 4 results from mutations in the SLC40A1 gene

Secondary Hemochromatosis is usually is the result of another disease or condition that causes iron overload. Examples of such diseases and conditions include:

Certain types of anemia, such as thalassemias and sideroblastic anemia
Atransferrinemia and aceruloplasminemia—both are rare, inherited diseases
Chronic liver diseases, such as chronic hepatitis C infection, alcoholic liver disease, or nonalcoholic steatohepatitis (NASH)
Blood transfusions
Oral iron pills or iron injections, with or without very high vitamin C intake (vitamin C helps your body absorb iron)
Long-term kidney dialysis (NHLBI n.d.)

Risk factors

Hemochromatosis is one of the most common genetic diseases in the United States. It's most common in Caucasians of Northern European descent. The disease is less common in African Americans, Hispanics, Asians, and American Indians.
Primary hemochromatosis is more common in men than in women. Also, older people are more likely to develop the disease than younger people. In fact, signs and symptoms usually don't occur in men until they're 40 to 60 years old
In women, signs and symptoms usually don't occur until after the age of 50 (after menopause). Young children rarely develop hemochromatosis.
Inheriting two faulty HFE genes (one from each parent) is the major risk factor for hemochromatosis. However, many people who have two copies of the faulty gene don't develop signs or symptoms of the disease.
Alcoholism is another risk factor for hemochromatosis. A family history of certain diseases and conditions also puts you at higher risk for hemochromatosis. Examples of such diseases and conditions include heart attack, liver disease, diabetes, arthritis, and erectile dysfunction (impotence).

Screening

Not everyone who inherits hemochromatosis genes develops symptoms or complications of the disease. 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.

Signs, Symptoms, and Complications

Signs and symptoms of hemochromatosis usually don't occur until middle age. Women are more likely to have general symptoms first, such as fatigue (tiredness). In men, complications such as diabetes or cirrhosis often are the first signs of the disease.

Signs and symptoms also vary based on the severity of the disease. Common signs and symptoms of hemochromatosis include joint pain, fatigue, general weakness, weight loss, and stomach pain.

Not everyone who has hemochromatosis has signs or symptoms of the disease. Estimates of how many people develop signs and symptoms vary greatly. Some estimates suggest that as many as half of all people who have the disease don't have signs or symptoms.

Hemochromatosis Complications
If hemochromatosis isn't found and treated early, iron builds up in your body and can lead to:

Liver disease, including an enlarged liver, liver failure, liver cancer, or cirrhosis

Heart problems, including arrhythmias and heart failure

Diabetes, especially in people who have a family history of diabetes

Joint damage and pain, including arthritis

Reproductive organ failure, such as erectile dysfunction (impotence), shrinkage of the testicles, and loss of sex drive in men, and absence of the menstrual cycle and early menopause in women

Changes in skin color that make the skin look gray or bronze

Underactive pituitary and thyroid glands

Damage to the adrenal glands

Diagnosis

Based on medical and family histories, a physical exam, and tests and procedures results.

Blood Tests

Transferrin saturation (TS),

Serum ferritin level,

Liver function tests

Liver Biopsy (less common now than in the past).

Magnetic Resonance Imaging (can show the amount of iron in the liver)

Superconducting Quantum Interference Device (SQuID) more sensitive to iron content than MRI

Genetic Testing

Genetic testing can show a faulty HFE gene or genes. However, even two faulty HFE genes 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 blood sample.

A genetic counselor also can help figure out the likelihood of the parents passing the faulty genes on to their children.

Treatment

Treatments for hemochromatosis include therapeutic phlebotomy, iron chelation therapy, dietary changes, and treatment for complications.

The goals of treating hemochromatosis include:

Reducing the amount of iron in your body to normal levels
Preventing or delaying organ damage from iron overload
Treating complications of the disease
Maintaining a normal amount of iron in your body for the rest of your life

Andres, J., Diamond, A., Miller, K. A., Omecene, N. E., Lisi, D., Morris, M., Givans, H., Chaney, A., Zappas, M., & Cocchiaro, B. (2021). Liver. Springer Publishing. Retrieved November 9, 2021, from https://connect.springerpub.com/content/book/978-0-8261-7708-7/chapter/ch14.

Porter JL, Rawla P. Hemochromatosis. [Updated 2021]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430862/

U.S. Department of Health and Human Services. (n.d.). Hemochromatosis. National Heart Lung and Blood Institute (NHLBI). Retrieved November 9, 2021, from https://www.nhlbi.nih.gov/health-topics/hemochromatosis.