Questions & Answers about Hemochromatosis

What is iron overload.what is hemochromatosis?

Iron overload is a condition in which the body accumulates too much iron. Humans extract needed iron from the diet, but when the regulation of intestinal iron absorption is altered, the body can absorb too much iron, leading to iron overload. Excess iron is deposited in the cells of the liver, heart, pancreas, joints, and pituitary gland. If left untreated, organ damage can result. In the United States, the most common cause of iron overload is a genetic disorder known as "hereditary hemochromatosis." People with hereditary hemochromatosis have an inherited propensity to over-absorb iron. Occasionally, some patients become iron-overloaded after years of excessive iron ingestion or with repeated blood transfusions, but most cases are genetic.

What are the signs and symptoms of hemochromatosis?

In the early stages of hemochromatosis, symptoms are non-specific and can include fatigue, palpitations, joint pain, non-specific stomach pain, and impotence, as well as loss of menstruation and infertility. Abnormalities of liver function tests can also occur in the absence of symptoms. The signs and symptoms of advanced hemochromatosis include gray or bronze skin pigmentation, cirrhosis of the liver, liver cancer, diabetes, heart disease, joint disease, chronic abdominal pain, sever fatigue and certain infections. Death may result from cardiac arrhythmia, congestive heart failure, diabetes, liver failure, and liver cancer.

What kind of health complications can the disease cause?

The later signs and symptoms include skin pigmentation, cirrhosis of the liver, liver cancer, diabetes mellitus, heart disease, joint disease, severe fatigue, and chronic abdominal pain.

Are there certain conditions that only hemochromatosis victims suffer?

The bronzing pigmentation associated with the later stage of hemochromatosis is the only unique sign of the disorder but not all affected individuals develop this complication. Unfortunately, there is no sign or symptom or constellation of signs and symptoms specific for hemochromatosis. Therefore, the diagnosis of hemochromatosis can be missed unless specific tests (serum iron measures) are conducted.

Who is most at risk for the disorder?

Siblings of persons with the disorder have a 25% chance of being affected. Children of persons with the disorder have a 5% chance of being affected. Persons who have the signs and symptoms compatible with hemochromatosis (such as severe weakness or fatigue, unexplained joint or abdominal pain, signs of liver disease, diabetes or heart problems, or elevated iron measures, impotence in men or loss of menstrual periods) may be at risk. These individuals should talk with their physicians about the possibility of being evaluated for hemochromatosis.

At what ages do people experience the symptoms/complications of hemochromatosis?

The symptoms/complications of hemochromatosis typically occur in middle-age, but these also can occur earlier in some people. The disease progression appears to vary in each individual. It is possible that a substantial proportion of people with early iron-overload remains healthy without treatment for many years, while a smaller proportion of people progress more rapidly through the course of their disease and develops life-threatening complications early. Therefore, further studies are necessary to gain an understanding of the clinical course of hemochromatosis among different individuals and to gain a better understanding of factors that modify disease progression.

How is hemochromatosis detected?

Short answer:
A simple routine blood test is used to identify indicate people at increased risk of iron overload. The test usually used for this purpose is transferrin saturation. If the initial test comes back elevated, then a repeat test is conducted after an overnight fast. If both tests are elevated, further tests are conducted to determine if iron overload is present. These tests may include a liver biopsy.

Long answer:
High transferrin saturation is the earliest manifestation of hereditary hemochromatosis. However, not all persons with high transferrin saturation values have the disorder. To assess the presence of iron overload, serum ferritin is also measured. If this is also elevated, iron overload is likely. Confirmation of iron overload is measured directly through liver biopsy to measure the amount of iron per gram of liver tissue, or through quantitative phlebotomy, the sequential removal of 1-2 units of blood per week until a low normal serum ferritin is achieved. Iron overload is considered to be present if this procedure results in the removal of 5 gms. (or 20 units) in males or 3 gms. (or 12 units) in females before reaching low levels of serum ferritin.

(For more details, refer to the 1 December 1998 Annals of Internal Medicine supplement).

Note: Transferrrin is a protein that transports iron in the blood. Individuals with high transferrin saturation values may or may not yet have iron overload.

Transferrrin saturation = (serum iron / total iron binding capacity (TIBC)) X 100

Is CDC telling people to go out and get tested?

At this time, CDC recommends that if an individual has a close blood relative with hemochromatosis or if an individual experiences the signs and symptoms compatible with hemochromatosis (such as severe weakness or fatigue, unexplained joint or abdominal pain, signs of liver disease, diabetes or heart problems, or elevated iron measures or liver function tests), that they talk with their regular physician about the possibility of being evaluated for hemochromatosis. Testing is recommended if there is no other identified cause for these medical problems.

How many people have hemochromatosis?

It is estimated that 1 in every 200 - 500 people in the United States has hereditary hemochromatosis.about 1 million people. Whites of northern European descent are at highest risk and men are more commonly affected than women, who may be protected by iron loss through menstruation and pregnancy.

How do you treat hemochromatosis?

Hemochromatosis is one of the few genetic diseases for which a simple effective therapy exits. Hemochromatosis is treated by removing blood (phlebotomy) from the patient in order to lower the level of iron. There is an initial de-ironing phase, where the patients have frequent phlebotomy to remove the accumulated iron. The frequency and duration of this process varies among individual patients, but typically consists of the removal of 1-2 units of blood per week for several weeks. Phlebotomy treatment is continued until iron concentrations come within normal limits. After this period, additional phlebotomy is performed on an "as needed basis" to keep iron levels within normal limits. When phlebotomy is begun early in the course of the illness, it can prevent most late symptoms and complications. Even when started after complications have occurred, phlebotomy can decrease symptoms and improve life expectancy.

Is it safe for people with hemochromatosis to donate blood?

The Food and Drug Administration (FDA) recently announced that blood from therapeutic phlebotomies for persons with hemochromatosis could be used for transfusion if certain criteria were met: 1) the blood collection center may not charge for the therapeutic phlebotomy and 2) the blood center must apply to FDA for exemption from existing regulations. As part of that exemption, the blood center must collect and submit specified data to the FDA. The FDA will consider exemption applications on a case-by-case basis.

Additional questions should be referred to the FDA.

Should a hemochromatosis patient eat iron fortified food?

Hemochromatosis patients do not need to avoid iron containing foods. It is strongly recommended that persons with hemochromatosis NOT take vitamin-mineral dietary supplements that contain iron and Vitamin C. In addition, they should not eat raw shellfish, and they should not use alcohol.

What causes this disorder?

Hereditary hemochromatosis is an inherited condition. It occurs when a person inherits two copies of a mutation in the HFE gene, one from each parent. People with one copy of an HFE mutation are carriers for the condition and usually have little or no excess accumulation of iron. It is estimated that 10% of the population are carriers for hemochromatosis. However, not all people with two genetic mutations develop signs and symptoms of the disorder.

Is iron overload only genetic?

It is possible that some patients become iron-overloaded after years of excess iron ingestion, but most cases are genetic. Iron overload can also occur with repeated blood transfusions.

History

Although hemochromatosis was first described in the medical literature over 100 years ago, the cause of the disease - iron accumulation, leading to damage of healthy tissues, was not initially known, and the disease was recognized only in its late stages. Over the past 15 years, studies have shown that people with early evidence of iron accumulation can be identified through blood tests (serum iron measures such as transferrin saturation and serum ferritin).

More recently, the gene associated with hereditary hemochromatosis, HFE, was identified in 1996. Several HFE mutations have been described. One of these mutations, C282Y, accounts for the majority of cases of hereditary hemochromatosis. Both serum iron measures and genetic testing are imperfect screening tools. Both may miss some people who are affected and also identify many people who are likely to remain well without treatment. In addition, the early symptoms and signs of hemochromatosis are non-specific; as a result, diagnosis can be difficult. At this time, one of CDC's top priorities is health-care provider education, to heighten awareness and aid health-care providers to recognize and treat this disorder.

CDC and Hemochromatosis

CDC sponsored a 3-day meeting of experts to discuss the many complex issues surrounding hemochromatosis. The summary of this meeting was published in the December 1998 Annals of Internal Medicine. The work of understanding the molecular genetics of hemochromatosis is underway, but many unresolved issues still remain. Most importantly, there are very few data on persons who were diagnosed with hemochromatosis on the basis of screening or early symptoms. We do not yet have a clear understanding of how the disease progresses in people who test positive by either serum iron measures or a test for hemochromatosis mutations. Some people with positive tests are likely to remain healthy without treatment; for them, screening would lead to unnecessary treatment and also to the potential for discrimination on the basis of a genetic diagnosis.

We are carefully reviewing the many issues related to screening, diagnosis, and treatment of hemochromatosis before we make any recommendations on a population basis. CDC does not recommend universal screening for hemochromatosis for the following reasons:

1. Uncertainty about disease progression
   To date, there are not sufficient data to determine what proportion of people identified with iron-overload through transferrin saturation screening will develop the complication of iron-overload. Without this information, it is not possible to determine the benefits of screening versus the potential for screening that could lead to unnecessary treatment.

2. Laboratory issues for diagnosis
   Different methods are available for measuring transferrin saturation and serum ferritin. Variation in results from different laboratories has been observed. In addition, there is no universally accepted cut-off point indicating iron-overload. Universal screening will require a standardized, reliable method for these laboratory measurements. CDC is conducting a study to compare analytic methods for measuring iron overload among national and international laboratories, as the first step in improving diagnostic approaches. Similar issues must also be addressed for genetic testing.

3. Potential for harm from hemochromatosis diagnosis
   People diagnosed with hemochromatosis may face difficulties acquiring health, life, or disability insurance, or they may face discrimination based on having a genetic condition. Personal and family distress may occur. In addition, current blood safety policy makes it difficult for individuals with hemochromatosis to donate blood. These potential harms indicate the need for strong evidence of benefit before universal screening is undertaken.

4. Impact of screening
   The impact of screening on primary care practices has not been evaluated.

5. Need to insure follow-up care of patients
   If screening is recommended, efficient tracking of individuals testing positive must be developed to assure that appropriate and continuing follow-up care is provided and patient confidentiality is preserved.
   
   CDC is currently developing educational materials to increase health care provider awareness of hemochromatosis.
   
   In addition, CDC is conducting a study to compare analytic methods for measuring iron overload among national and international laboratories. These results will be crucial for refining, standardizing, and monitoring laboratory tests for iron status.