MedicineNet.com

About Us | Privacy Policy | Site Map
February 10, 2012

Iron Overload (cont.)

Medical Author:
Medical Editor:

What are the symptoms and signs of hemochromatosis?

Patients with early hemochromatosis have no symptoms and are unaware of their condition. The disease may then be discovered when elevated iron blood levels are noted by routine blood testing. In men, symptoms may not appear until 40-50 years of age. Iron deposits in the skin cause darkening of the skin. Since females lose iron through menstrual blood loss, they develop organ damage from iron accumulation 15 to 20 years later than men on average.

Iron deposits in the pituitary gland and testicles cause shrinkage of the testicles and impotence. Iron deposits in the pancreas cause a decrease in insulin production resulting in diabetes mellitus (please read the Diabetes Mellitus article). Iron deposits in the heart muscle can cause heart failure as well as abnormal heart rhythms. Iron accumulation in the liver causes scarring of the liver (cirrhosis) and an increased risk of developing liver cancer. For further information on the consequences of cirrhosis, please read the Cirrhosis article.

How is hemochromatosis diagnosed?

Most patients with hemochromatosis are diagnosed early and have no symptoms. Their hemochromatosis is discovered when elevated levels of iron in the blood are found as part of routine blood testing; or when blood iron levels are measured as in screening studies in family members of patients with hereditary hemochromatosis. Some patients are diagnosed as having hemochromatosis when their doctors perform blood iron levels as part of the evaluation for abnormal elevations in blood levels of liver enzymes AST and ALT.

Blood iron tests

There are several blood tests that reflect the amount of iron in the body; ferritin level, iron level, total iron binding capacity (TIBC), and transferrin saturation.

Ferritin is a blood protein whose levels correlate with the amount of iron stored in the body. Blood ferritin levels usually are low in patients with iron deficiency anemia, and are high in patients with hemochromatosis and other conditions that cause an increase in body iron levels. Since ferritin also can be elevated in certain infections such as viral hepatitis and other inflammatory conditions in the body, an elevated ferritin level alone is not sufficient to accurately diagnose hemochromatosis.

Serum iron, TIBC, and transferrin saturation are often performed together. Serum iron is the measure of the amount of iron in serum (the liquid portion of the blood). TIBC is a measure of the total amount of iron that can be carried in serum by transferrin, a protein that carries iron in serum from one part of the body to another. Transferrin saturation is a number calculated by dividing serum iron by TIBC—it is a number that reflects what percentage of the transferrin that is being used to transport iron. In healthy individuals the transferrin saturation is between 20 and 50 percent. In patients with iron deficiency anemia, the serum iron and transferrin saturation are abnormally low; and in patients with hereditary hemochromatosis the serum iron and transferrin saturation are abnormally high.

Since serum iron can be elevated by eating and can fluctuate during the day, serum iron measurements should be done fasting, usually in the morning before breakfast.

Liver biopsy

The most accurate test for diagnosing hemochromatosis is measurement of the iron content of liver tissue obtained by a biopsy. A liver biopsy involves the removal of a sample of liver tissue for analysis and is usually performed with a needle under local anesthesia. After numbing the skin and the underlying tissues, the doctor inserts the needle into the liver through the right lower rib cage, sometimes under ultrasound guidance. The tissue obtained by the needle is studied under a microscope for signs of active liver disease, fibrosis and cirrhosis (permanent scarring), and iron content (usually significantly elevated in hemochromatosis).

The liver biopsy also has prognostic value because it determines whether the patient already has irreversible advanced cirrhosis. Patients with hemochromatosis but an otherwise normal liver biopsy have longevity similar to other healthy adults if adequately treated, while patients with cirrhosis as a result of hemochromatosis have significantly reduced longevity. Furthermore, the risks of cirrhotic patients developing liver cancer (hepatocellular carcinoma) are substantially higher than normal subjects even with adequate treatment of the iron overload with phlebotomy (see below).

Genetic Tests

The gene for hereditary hemochromatosis was identified in 1996. The gene is referred to as the HFE gene. Hereditary hemochromatosis is associated in most patients with two mutations of the HFE gene; C282Y and H63D.

A C282Y homozygote is a person who has inherited one mutated C282Y gene from each parent. A C282Y homozygote is considered at risk of developing iron overload. In fact, C282Y homozygotes account for 95% of all hereditary hemochromatosis. Conversely, not every C282Y homozygote develops iron overload. Studies have shown that an estimated 50% of C282Y homozygotes may not develop iron overload or its complications.

A C282Y/H63D compound heterozygote is a person who has inherited one mutated C282Y gene from one parent and a second mutated H63D gene from the other parent. Most compound heterozygotes have normal iron levels though some can develop mild to moderate iron overload.

A C282Y heterozygote is a person who has inherited one mutated C282Y gene from one parent but a second normal HFE gene from the other parent. Children born of two C282Y heterozygotes have a 25% chance of being a C282Y homozygote and, therefore, will be at risk of developing hemochromatosis. A C282Y heterozygote does not develop iron overload.

An algorithm for diagnosing hereditary hemochromatosis is as follows:

  1. Adults suspected of having hereditary hemochromatosis (for example, adult, first-degree relatives of a patient with hereditary hemochromatosis) are subjected to measurements of fasting serum iron, TIBC, transferrin saturation and ferritin.

  2. Patients with elevated serum iron, ferritin, and transferrin saturation of greater than 45% are subjected to genetic testing

  3. Patients with transferrin saturation greater than 45% who are C282Y homozygotes have hemochromatosis and, therefore, should be treated with therapeutic phlebotomy (see below).

Who should undergo liver biopsy?

Not all patients with hemochromatosis need to undergo liver biopsy. The purpose of liver biopsy is to identify those patients with cirrhosis and to exclude other possible liver diseases. (Patients with hemochromatosis and cirrhosis are at increased risk of complications, especially liver cancer.)

Young patients (<40 years of age) who are C282Y homozygotes with normal liver blood levels and serum ferritin levels <1000 ng/ml have a very low risk of having cirrhosis of the liver. Therefore, these patients can be treated with therapeutic phlebotomy without a liver biopsy. Their prognosis is excellent with adequate treatment.

Older patients (>40 years of age) who have serum ferritin levels >1000 ng/ml, and have abnormally elevated liver blood levels may already have developed cirrhosis. Doctors may recommend liver biopsies in these patients provided that it is safe for them to undergo liver biopsy.


Patient Discussions

Viewers share their comments

Iron Overload - Symptoms Question: What were the symptoms and signs with your hemochromatosis (iron overload)?

MedicineNet Doctors

Suggested Reading on Hemochromatosis (Iron Overload) by Our Doctors

  • Related Diseases & Conditions

    • Congestive Heart Failure
      • Congestive heart failure (CHF) is a condition in which the heart's function as a pump is inadequate to meet the body's needs. A poor blood supply resulting from congestive heart failure may cause the body's organ systems to fail, leading to a weakened heart muscle and fluid accumulation in the lungs and body tissue. There are many diseases that can impair pumping efficiency and symptoms of congestive heart failure including fatigue, diminished exercise capacity, shortness of breath, and swelling. Treatments include lifestyle modifications, medications, heart transplant, and therapy.
    • Liver Cancer
      • Liver cancer is the fifth most common cancer in the world and the majority of patients with liver cancer will die within one year as a result. Patients with associated cirrhosis caused by chronic hepatitis B or C infections, alcohol, and hemochromatosis are at the greatest risk of developing liver cancer. Many patients with liver cancer do not develop symptoms until the advanced stages of the tumor which usually makes prognosis poor. The combination of an imaging study (ultrasound, CT, or MRI scans) and an elevated blood level of alpha-fetoprotein will most effectively diagnose liver cancer, while a liver biopsy can make a definitive diagnosis. Medical treatments, including chemotherapy, chemoembolization, ablation, and proton beam therapy, are not very effective. Surgical removal of the tumor or a liver transplant may be most effective in certain cases.
    • Cirrhosis (Liver)
      • Cirrhosis of the liver refers to a disease in which normal liver cells are replaced by scar tissue caused by alcohol and viral hepatitis B and C. This disease leads to abnormalities in the liver's ability to handle toxins and blood flow, causing internal bleeding, kidney failure, mental confusion, coma, body fluid accumulation, and frequent infections. Symptoms include yellowing of the skin, itching, and fatigue.
    • Diabetes (Type 1 and Type 2)
      • Diabetes mellitus is a chronic condition characterized by high levels of sugar (glucose) in the blood. The two types of diabetes are referred to as type 1 (insulin dependent) and type 2 (non-insulin dependent). Symptoms of diabetes include increased urine output, thirst, hunger, and fatigue. Treatment of diabetes depends on the type.
    • Liver Disease
      • Liver disease can be cause by a variety of things including infection (hepatitis), diseases such as gallstones, high cholesterol or triglycerides, blood flow obstruction to the liver, and toxins (medications and chemicals). Symptoms of liver disease depends upon the cause; however, common symptoms may include nausea, vomiting, upper right abdominal pain, and jaundice. Treatment depends upon the cause of the liver disease.
    • Palpitations
      • Palpitations are unpleasant sensations of irregular and/or forceful beating of the heart. Palpitations can be relieved in many patients by stress reduction, stopping cigarettes, and reduction of caffeine and alcohol.
    • Arthritis
      • Arthritis is inflammation of one or more joints. When joints are inflamed they can develop stiffness, warmth, swelling, redness and pain. There are over 100 types of arthritis including osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, lupus, gout, and pseudogout.
    • Erectile Dysfunction (Impotence)
      • Impotence, also known as erectile dysfunction, is a common problem among men characterized by the consistent inability to sustain an erection sufficient for sexual intercourse or the inability to achieve ejaculation, or both. Impotence can have emotional causes but most often it is due to a physical problem.
    • Testicular Pain (Pain in the Testicles)
      • Testicular pain, or pain in the testicle or testicles are caused by a variety of diseases or conditions such as testicular trauma, testicular torsion, testicular cancer, epididymitis, and orchitis. Common symptoms of pain in the testicle or testicles are abdominal pain, urinary pain or incontinence, fever, nausea, vomiting, and pain in the scrotum or testicle. Treatment depends on the cause of the testicular pain or pain in the testicles.
    • Liver
      • The liver is the largest solid organ in the body, and is actually an gland. The liver has a wide variety of critical functions such as manufacturing proteins and metabolizing fats and carbohydrates. The liver also eliminates harmful biochemical waste products from the body (alcohol, drugs, toxins). The liver secretes bile that aids in digestion. Examples of diseases of the liver include cirrhosis, hepatitis, cancer, and fatty liver. Symptoms of liver disease include bleeding, easy bruising, edema, fatigue, and jaundice.
    • Pseudogout
      • Pseudogout, a form of arthritis, results when deposits of crystals collect in and around the joints. Symptoms of pseudogout include pain, stiffness, warmth, and joint swelling of the knees, ankles, hips, shoulders, and/or wrists. Treatment for pseudogout aims to decrease inflammation through the use of nonsteroidal antiinflammatory drugs, ice, and rest.
    • Beta Thalassemia
      • Beta Thalassemia is the most familiar type of thalassemia. Thalassemia is not just one disease but rather a complex series of genetic (inherited) disorders all of which involve underproduction of hemoglobin.
    • Iron Deficiency
      • Iron is a mineral our bodies need. Iron deficiency is a condition resulting from not enough iron in the body. It is the most common nutritional deficiency and the leading cause in the US. Iron deficiency is caused due to increased iron deficiency from diseases, nutritional deficiency, or blood loss and the body's inability to intake or absorb iron. Children, teen girls, pregnant women, and babies are at most risk for developing iron deficiency. Symptoms of iron deficiency include feeling weak and tired, decreased work or school performance, slow social development, difficulty maintaining body temperature, decreased immune function, and an inflamed tongue. Blood tests can confirm an iron deficiency in an individual. Treatment depends on the cause of the deficiency. Proper diet that includes recommended daily allowances of iron may prevent some cases of iron deficiency.
    • The Digestive System
      • Digestion is the complex process of turning food you eat into the energy you need to survive. The digestive process also involves creating waste to be eliminated, and is made of a series of muscles that coordinate the movement of food.
  • Medications

  • Procedures & Tests

  • Pictures, Images & Illustrations

  • Doctor's & Expert's Views

  • Health News

  • Health Features

Women's Health

Find out what women really need.



Symptom Checker: Your Guide to Symptoms & Signs: Pinpoint Your Pain









Use Pill Finder Find it Now

Pill Identifier on RxList

  • quick,
    easy,
    pill identification

Find a Local Pharmacy

  • including
    24 hour
    pharmacies