HEMATOLOGY
Hemochromatosis is a condition that causes excess absorption of iron from the digestive tract. Over time, excess iron accumulates in tissues throughout the body leading to iron overload. Signs of iron overload may include joint pains, weakness, sexual dysfunction, changes in skin coloration, liver damage (cirrhosis), heart failure, diabetes mellitus and rarely thyroid disease or liver cancer.
GENETIC TESTING can reveal the presence of gene defects associated with hemochromatosis. Symptoms usually occur in people who have inherited two copies of gene defects, the most common of which are called C282Y mutations.
Causes
A number of chemical events take place that regulate how much iron is absorbed. Central to this process is a gene called HFE. Mutations in this gene cause excessive amounts of iron to be absorbed.
Hemochromatosis is most often seen in people who have two copies of this mutation (one inherited from their mother and another from the father). Other mutations causing hemochromatosis continue to be discovered.
Risk Factors
Hemochromatosis is usually found in people who are white. In the United States, five in every 1,000 Caucasians have the condition, so it’s probably the most common disease you’ve never heard of.
Because it is an inherited condition and specific symptoms may not manifest, family members of people with hemochromatosis should undergo testing. About 10 percent of Caucasians carry one of the gene defects associated with hemochromatosis, although most of these people have no symptoms.
Symptoms
Symptoms usually occur in people who have inherited two copies of gene defects, the most common of which are called C282Y mutations. The relationship between the gene defects and iron accumulation is still being explored.
Most people with hemochromatosis today are identified at a young age because of abnormalities on routine blood tests or because they undergo testing after a family member is diagnosed. As a result, 75 percent of people with hemochromatosis are diagnosed before they have symptoms and most people do not have complications at the time of diagnosis.
Cirrhosis can cause a number of complications and can ultimately lead to liver failure or death. People with liver cirrhosis are at risk of developing liver cancer.
Symptoms typically do not occur until age 40, and tend to appear later in women than men because women lose iron through their lives through menstrual periods, pregnancy and breast-feeding.
Accumulation of iron in the liver can cause liver enlargement, cirrhosis and fibrosis. Cirrhosis can cause a number of complications and can ultimately lead to liver failure or death. People with liver cirrhosis are at risk of developing liver cancer.
Liver disease is often worse in people with hereditary hemochromatosis who have chronic hepatitis (hepatitis B or C) or who are alcoholics.
Seventy five percent of people have a feeling of mental and physical sluggishness.
Hemochromatosis can increase risk of infection with specific types of bacteria. Accumulation of iron in immune cells interferes with their ability to fight off certain bacteria, and other bacteria grow well in an iron-rich environment.
Physical Changes
- Darkening of the skin – Accumulation of iron in the skin along with accumulation of pigment melanin, can darken the skin and give a person a tanned appearance. Seventy percent of people who have symptoms at the time of diagnosis have darkening of their skin.
- Joint pain – Excess iron leads to collection of calcium crystals in the joint spaces. These crystals can cause joint pain and joint deformity over time as the hands are most commonly affected.
- Diabetes mellitus – Accumulation of iron in the pancreas can interfere with insulin production and cause diabetes. About one-half of people who have symptoms at time of diagnosis have diabetes.
- Reproductive problems – Accumulation of iron in the pituitary gland can interfere with the pituitary’s control of sex hormones. In men, pituitary damage can lead to impotence and loss of libido. In women, pituitary damage can cause amenorrhea (absence of menstrual periods).
- Heart disease – Accumulation of iron in the heart can cause enlargement of the heart, abnormal electrical conduction of the heart, even heart failure. About a third of people who have symptoms at time of diagnosis have conduction problems, which may cause symptoms of rapid or irregular heart beat. Rarely, heart disease is the first sign of hemochromatosis.
- Thyroid disease – Accumulation of iron in the thyroid gland can cause hypothyroidism in about 10 percent of patients.
Diagnosis
- Genetic tests – Genetic testing can reveal the presence of gene defects associated with hemochromatosis.
- Liver biopsy – Liver biopsy is the best test to determine if and how much of the liver is affected by hemochromatosis. In some cases liver biopsy is not necessary because other tests are able to confirm the diagnosis.
- Blood tests – Three blood tests are recommended:
- Iron levels. Most people with hemochromatosis have elevated levels of iron in the blood
- Transferrin saturation. This is a protein that binds iron and transfers it between the tissues. Transferrin saturation is one of the most sensitive tests for detecting early hemochromatosis.
- Ferritin levels. Ferritin is a protein that reflects the body’s stores of iron. Ferritin levels greater than 300 ng/ml in men and 200 ng/ml in women support a diagnosis of hemochromatosis. However, ferritin levels can also be increased by many common disorders other than hemochromatosis.
Treatment
Treatment of hemochromatosis requires removal of excess iron from the body by periodically removing blood (phlebotomy). This can prevent complications and even reverse some complications, and over time will, return iron stores back to normal levels.
Treatment of hemochromatosis requires removal of excess iron from the body by periodically removing blood (phlebotomy)
The decision to begin phlebotomy is usually based on a person’s age, sex and level of ferritin. This procedure is generally safe and can be performed in a clinician’s office, blood bank, hospital or even a person’s home. Typically one unit of blood, or 1 pint, is removed per week. However, 1.5 to 2 units of blood can be removed from men.
Iron levels are usually monitored every four to eight weeks during treatment in order to determine when the excess iron stores have been depleted. If anemia occurs, phlebotomy may be temporarily stopped.
In people with hemochromatosis who do not have symptoms at the time of diagnosis, the excess iron stores are depleted to normal after about 30 or fewer phlebotomy sessions. In those who have symptoms at the time of diagnosis, 50 or more phlebotomy sessions may be needed to deplete excess iron stores. Each unit of blood drops ferritin by about 30 ng/ml.
After iron stores have been reduced to normal levels, maintenance phlebotomy ( emoving one unit of blood every two to four months) is essential to prevent iron from accumulating again.
Benefits of Phlebotomy
- Prevent complications of iron overload in people who do not have complications
- Help to ensure a normal life expectancy
- Prevents potentially life-threatening complications of liver cancer and liver cirrhosis
- Resolve or improve weakness, fatigue, lethargy, darkening of skin, high blood ferritin levels, improve poor liver function, liver enlargement and liver pain
- Reverse liver disease when it is in an early stage
- Resolve joint pain and heart disease in early stages
- Phlebotomy only rarely improves joint deformity, pituitary disease, susceptibility to certain infections, diabetes, or thyroid disease. It does not reverse liver cirrhosis or lessen the risk of liver cancer that is associated with liver cirrhosis.
- Dietary considerations. Patients who are receiving treatment for hemochromatosis do not have to follow a special diet. However, they should avoid iron supplements and vitamin C supplements, which promote iron absorption. Alcoholic beverage can be consumed in moderation. People with hemochromatosis should avoid eating uncooked seafood because it may contain bacteria that grow well in an iron-rich environment.
- Chelation therapy. Chelation therapy refers to treatment with the drug deferoxamine or deferosirox. This drug tightly binds to iron and removes it from the body, lowering iron stores. Chelation therapy is seldom used because phlebotomy is a simpler and equally effective treatment.
There is a 25 percent chance that a full brother or sister of a person with hereditary hemochromatosis will have the same.
Although phlebotomy can alleviate or even completely resolve some complications of hemochromatosis, other measures may be necessary to treat complications that persist. For example, liver disease may eventually require liver transplantation and diabetes may require insulin therapy.
Implications for the Family
Hemochromatosis is almost always caused by a genetic mutation that is passed from both parents to a child. Therefore, clinicians usually recommend that first-degree relatives of people with hemochromatosis undergo screening. There is a 25 percent chance that a full brother or sister of a person with hereditary hemochromatosis will have the same.
The primary goal of screening is to detect hemochromatosis before there are any symptoms or complications. Optimal age of screening is between 18 and 30 years of age. Most people with hemochromatosis have a normal life expectancy, however, survival may be shortened in people who develop cirrhosis or diabetes mellitus.
Dr. Dalal
ABOUT THE AUTHOR
Dr. Dalal
Dr. Dalal has been a physician at Space Coast Cancer Center in Brevard County, Florida since 2003. He graduated from the M.S. University Medical College of Baroda, Gujarat India, and was a clinical research associate in the Department of Oncology at Montifiore Medical Center in Bronx, New York. Dr. Dalal completed his residency in internal medicine and a three year fellowship in hematology/oncology at Beth Israel Medical Center in New York.
Dr. Dalal is board certified in internal medicine, hematology, and medical oncology and is a member of the American Society of Clinical Oncology and the Florida Society of Clinical Oncology. His office locations include Titusville, Merritt Island and Rockledge. Dr. Dalal is an avid tennis player and musician – and enjoys spending time with his family.
To reach Dr. Dalal call 321-268-4200.
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