Hereditary hemochromatosis is a manic disorder in which individuals absorb slightly more iron than normal. This process occurs over decades. However, tissue damage occurs after significant amounts of iron have been absorbed. In most cases, the individual has absorbed approximately 15-20 grams of iron. It is at this amount of absorbed iron in which patients begin to have tissue damage. Also, it is at this amount of absorbed iron that produces significant organ system damage in individuals.
Hereditary hemochromatosis is thought to occur with equal frequency in both sexes. However, since regular blood loss through normal menses occurs in females, the preponderance of cases is in males. This approximates 8-1 male to female ratio.
Recently, a test has been developed which detects the cellular or genetic abnormalities responsible for many cases of hemochromatosis.
The liver is the first site of iron overload in hereditary hemochromatosis. This is based on absorption of iron by the liver. When food is ingested, it is absorbed in the small intestine. This absorption passes into the veins that then form the portal vein. The portal vein then is directed to the liver. The portal vein then divides into small veins that provide the liver cells with nutrients absorbed from the intestine, thus, the liver is the first site in which iron absorption occurs. Typically, liver function tests are elevated in individuals.
As iron absorption continues, and the ability of the liver to store iron is exceeded, the heart, pancreas, joints and bones, skin and the immune system become affected.
Clinical Symptoms
Many patients do not have any evidence of clinical symptoms. However, right upper quadrant abdominal pain or vague abdominal pain is a common complaint in patients who have had significant iron overload. The pain is usually described as a dull discomfort or vague feeling in the right upper quadrant or area of the abdomen called the epigastrium. The pain is thought to be secondary to distention of the liver capsule that surrounds the liver. As patients are treated for hereditary hemochromatosis, this pain resolves.
In many patients, elevations in the liver function tests are identified during routine exam. Usually, these elevations are approximately 2 times normal. In approximately 50 percent of patients, an enlarged liver and spleen are also identified.
In most cases, elevated irons and abnormal liver function tests are identified earlier.
Complications of Hereditary Hemochromatosis
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Dysrhythmias: Iron is deposited in the conduction system of the heart that induces abnormal heart rhythms. These are commonly atrial tachycardia, ventricular tachycardia and ventricular premature beats. |
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Pancreatic and endocrine involvement: Many patients have deposits of iron in the pituitary gland. Subsequently, hormones (such as prolactin and FSH as well as luteinizing hormones) are abnormal. Thus, impotence and decreased libido as well as a decrease in body hair can be seen in some patients. In addition, pancreatic depositions have been identified. This results in diabetes mellitus. Patients who have cirrhosis due to hereditary hemochromatosis have a 20% chance of developing diabetes. |
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Joints and bones: Abnormal joints and bones occur in up to 45 percent of patients with hereditary hemochromatosis. This happens early on in the disease. It may involve joints of the fingers, knees, back and neck. X-rays are extremely useful for evaluation of these patients. In addition, osteoporosis is seen in many patients. There is a high association of pituitary dysfunction and osteoporosis. |
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Skin: Skin pigmentation occurs late in the disease. It appears to be a bronze type of discoloration. Skin biopsies can show deposition of iron and increased melanin. |
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Immune system: Patients with iron overload are susceptible to bacterial infections. In many cases, Yersinia and Vibrio are commonly associated with infections in patients with hereditary hemochromatosis. |
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Hepatocellular carcinoma: Once cirrhosis has been established in patients with hereditary hemochromatosis, the incidence of hepatocellular carcinoma is approximately 30 percent. Thus, the liver biopsy becomes extremely important in identifying patients who have documented cirrhosis. Patients without cirrhosis are usually at low risk, if any, for the development of hepatocellular carcinoma. Screening for hepatocellular carcinoma takes place in the form of routine ultrasound of the liver and measure of a tumor marker called an alphafetoprotein (AFP). |
In many patients, the diagnosis is made by the genetic test. Clinical tip-offs for this include an elevated ferritin. Ferritin is a measure of the entire body store of iron. Thus an elevated ferritin, when there is not a co-existing infectious process, may indicate the presence of hereditary hemochromatosis.
Liver biopsy has been a gold standard in the past. In patients over the age of 50, with a genetic marker that is positive for hereditary hemochromatosis, a liver biopsy is usually mandatory. This is to assess the degree of fibrosis or cirrhosis within an individual liver. In addition, an iron content can be calculated from this piece of tissue. This provides information for your physician so that he or she may estimate the amount of therapy you may require.
Therapy of Hereditary Hemochromatosis
The treatment for hereditary hemochromatosis is a phlebotomy. Phlebotomy refers to the removal of blood from the body. A large bore IV is usually placed in the antecubital veins of a patient. One unit of whole blood is removed. This is usually approximately 500 milliliters of blood. Within 500 milliliters of blood 200-250 mg of iron is present.
Most patients require routine phlebotomies on a weekly basis. Depending on the amount of iron that has been stored within an individual's body, this may take months to years to accomplish.
When iron stores are returned to normal, maintenance phlebotomy (usually between 1 phlebotomy every 3-4 months) can be instituted. Phlebotomy under these circumstances is a life long therapy.
Other forms of treatment include chelation therapy with deferoxamine. Deferoxamine is an expensive therapy. In addition, it removes smaller amounts of iron. This is approximately 60-80 mg per day. In many patients who have high iron contents, Deferoxamine becomes a less well tolerated treatment.
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