Hereditary hemochromatosis is a genetic disease that is the result of inheriting two defective copies of a particular gene, one from each parent. The mutation in this gene causes the intestine to absorb too much iron. 

What are the signs and symptoms of hemochromatosis?

In the early stages of hemochromatosis, symptoms are non-specific and mimic a variety of other disease symptoms.  Symptoms 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.  

What kind of health complications can the disease cause?

The later signs and symptoms include skin pigmentation, cirrhosis of the liver, liver cancer, 

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 every affected individual develops this complication.  Unfortunately, there is no sign or symptom or 

Who is most at risk for the disorder?   

Siblings of persons with the disorder have a 25% chance of carrying the mutations responsible for hereditary hemochromatosis, while children with one affected parent have a 5% chance of being affected.  When both parents have the disorder, children have a 100% chance of carrying the hereditary hemochromatosis mutations.  However, it is not known what proportion of these affected individuals will develop iron overload during

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

The symptoms/complications of hemochromatosis typically occur in middle-age, but 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 hemochromatosis remain healthy without treatment for many years, while a smaller proportion of people 

How is hemochromatosis detected? 

Short answer: 

A simple blood test is used to diagnose people with iron overload.  The test typically used for this purpose is transferrin saturation.  If the initial test comes back elevated (>45%), 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.  For more details, refer to the recommendations in the Annals of Internal Medicine Supplement, 1 December 1998,  page 955.   

Unfortunately, standard cut-off points for these tests have not yet been determined.  Although there is no agreement as to the standard transferrin cut-off value, most investigators suggest a value over 60% be considered abnormal, and values between 45% and 60% indicate iron overload is possible.  Serum ferritin values > 200 ug/L in premenopausal females and >300ug/L in males and post menopausal females are considered abnormal.  Since serum ferritin can be elevated for reasons independent of iron overload, this measurement alone does not necessarily reflect iron overload.  Both tests should be conducted to diagnose hemochromatosis. 

Long answer: 

High transferrin saturation is the earliest manifestation of hereditary hemochromatosis.  It is recommended that people with the symptoms compatible with hereditary hemochromatosis be tested.  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:  Transferrin is a protein that transports iron in the blood.  Individuals with high transferrin saturation values may or may not have iron overload. 

Is CDC telling people to go out and get tested? 

At this time, CDC recommends that testing be conducted if an individual has a close blood relative with hemochromatosis or if an individual experiences the signs or unexplained symptoms compatible with hemochromatosis (such as severe weakness or fatigue, unexplained joint or abdominal pain, signs of

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

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, during which 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 

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 iron overload could be used for transfusion if certain criteria are met: 1) the blood collection center may not charge for the therapeutic phlebotomy and 2) the blood center must apply to FDA for 

Additional questions should be referred to the FDA.  

Should a hemochromatosis patient avoid iron fortified food?

Hemochromatosis patients do not need to avoid iron containing foods.  It is strongly recommended that hemochromatosis patients NOT take vitamin-mineral dietary supplements that contain iron.  Similarly, no more than 500mg of vitamin C should be consumed because Vitamin C increases iron uptake.  Such patients should avoid anything else that has the

What causes hereditary hemochromatosis?   

Hereditary hemochromatosis is an inherited condition.  It occurs when a person inherits two copies of a mutation, one from each parent.  People with one copy of this mutation are carriers for the condition and usually have little 

Are there other disorders that cause iron overload?   

In the United States, the most frequent cause of iron overload is hereditary hemochromatosis.  However, there are rare genetic disorders that also result in iron overload such as neonatal 

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). 

In 1996, the gene associated with hereditary hemochromatosis, HFE, was identified. Several HFE mutations have been described, but the

Background

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, we do not yet have a clear understanding of how the disease progresses in

Current

Currently, 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 hemochromatosis through genetic testing, or iron-overload through transferrin saturation testing will develop the complications of iron-overload.  Without this information, it is not possible to determine the benefits of screening versus the potential risks resulting from unnecessary treatment.
2. Laboratory issues for diagnosis  
   Different laboratory 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.  The sensitivity and specificity of these tests are not yet known.  Similar issues must also be addressed for genetic testing.

3. Potential for harm from hereditary hemochromatosis diagnosis
   People diagnosed with hemochromatosis may face difficulties in acquiring health, life, or disability insurance, or they may face discrimination based on having a genetic condition. Personal and family distress may occur.  The ethical, legal and social implications of this genetic testing need to be understood.  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 on the health care system
   The impact of screening on primary care practices has not been evaluated.  The cost effectiveness of screening needs to be determined.  The costs of screening are not routinely covered by medical insurance.
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.

Current activities

In May 2000, CDC hosted a meeting of experts to develop educational materials to increase health care provider awareness of hemochromatosis.  The resulting educational content materials are being developed into CDC’s hemochromatosis/iron overload website (available in late 2001).