DOCTOR'S VIEW ARCHIVE
July has been designated Hemochromatosis Screening Awareness Month in the United States but the question all year long everywhere in the world is: Whether to screen or not to screen? That is the question that divides the health care professionals who care for people with hemochromatosis, a disorder commonly called iron overload.
The means to screen for iron overload are available. But they are not being used. Why? Because there is disagreement about whether screening should be done.
Some Areas of Agreement
There are several areas of agreement about iron overload (hemochromatosis). The condition is due to an inability to regulate iron absorption. Too much of the iron in food is absorbed from the intestine and passes into the blood stream. The extra iron accumulates in organs ever so slowly. Someone with hemochromatosis may typically have chemically detectable iron overload by age 30 but not experience even the first signs or symptoms of the disease (such as unusual weakness and fatigue, weight loss, bronzed skin (not caused by sunlight), joint and abdominal pains, impotence in men, and cessation of menstrual periods in women) until they are past 40.
There is also no disagreement about the genetic basis of hemachromatosis. About 1 in 9 people carries a gene for hemochromatosis but never develops the disease (although they can pass the gene along to their children) each child of a carrier runs a 25% risk of inheriting both of their hemochromatosis genes and joining the 1 in 300 Americans estimated to have the disease.
Gene Raises Screening Questions
A sensitive and relatively inexpensive screening test for iron overload has long been available in the form of what is called the transferrin saturation (TS) test. Two positive TS test results (above 60% in men or 50% in women) are suggestive of hemochromatosis. The diagnosis then must be confirmed, most commonly by a liver biopsy or systematic bloodletting to extract iron, a technique termed quantitative phlebotomy.
What started the controversy brewing over screening was the identification of the gene responsible for most cases of iron overload. The key research had begun in 1976 when it was recognized that there might possibly be an association between the hemochromatosis gene and the major transplantation genes (called HLA). The hemochromatosis gene was finally found in 1996. The symbol for the gene is HLA-H (HLAE) or, now preferably, HFE.
Once the HFE gene was identified, a test for it was devised and questions arose in earnest about the prospect of massive public health screenings for hemochromatosis.
Patients with the disease see an average of three doctors before being correctly diagnosed, according to the Centers for Disease Control (CDC). Advocates say screening could be a useful tool for identifying and treating the disease early.
What the Expert Panel Said
In March of 1997, the CDC and the National Human Genome Research Institute, part of NIH, convened an expert panel. The panel evaluated the potential of hemochromatosis screening. A report of their recommendations was published in July of 1998 in the Journal of the American Medical Association (JAMA).
The expert panel recommended against screening large populations for the disorder. Their recommendation was based on lack of information about how the gene is distributed within populations, how it affects different people, how the disease progresses, and how to care for people who have mutations of the gene but have no signs or symptoms of the disease. The panel also raised the issues of discrimination and stigmatization of people with the gene. They concluded that population-based research needs to be conducted to learn more about the disorder and how genes (and the environment) interact to cause the disorder to progress differently or not at all in some people.
A Panel Member Speaks
"We lack information about what proportion of people with hemochromatosis go on to develop cirrhosis (serious liver scarring). The question is, do we have the right picture of hemochromatosis as a liver disease 'causer'? I still agree with the article in JAMA that it's premature to use genetic screening," said Dr. Wylie Burke, MD, PhD, an associate professor of Medicine at the University of Washington and a member of the expert panel. Dr. Burke said there have been anecdotal cases of people being diagnosed with iron overload and losing their health insurance. She also pointed out that blood banks don't accept blood donations from people with hemochromatosis. The recommended therapy for iron overload involves regular blood draws to free the body of excess iron. This treatment is performed up to two times a week until the blood iron levels return to normal. After this time, treatment consists of regular monitoring of iron levels and annual blood draws. Burke said the cost of the blood draws ranges from $50 to $150 per treatment.
Where the U.S. Centers for Disease Control (CDC) Stands
In sum, the CDC is opposed to population screening for hemochromatosis. The CDC has further said, "The education of health care providers and patients with hemochromatosis is central to the public health plan of action and will necessarily include protecting patients from social discrimination and developing the means to decrease the therapeutic costs to patients for phlebotomy."
Who Should Be Tested?
The CDC recommendation against population screening for hemochromatosis does not mean that the relatives of patients with the disease should not be tested. Once the diagnosis of iron overload is made in someone, it is important that family members who are at elevated risk for the disorder be tested. Family members with possible symptoms and those without them, but who are at increased risk for the disorder, should all be tested for hemochromatosis.
Patient Advocate Voices Views
Randy Alexander, who has hemochromatosis and is the founder and president of the Iron Disorders Institute in Greenville, South Carolina, concurs with the CDC's conservative approach. He said, "The ethical, moral and legal ramifications of such practice (DNA population screening) has not yet been determined." Alexander lost his insurance after being diagnosed.
Dissenters on Record
However, not everyone agrees with the CDC position. An article in the Washington Post in July of 1998 portrayed families who had lost relatives from the disorder and criticized the CDC's stand on screening. Clinicians aren't all supporting the CDC position either. Dr. Kris Kowdley is the director of the Iron Overload Clinic at the University of Washington. Unlike his colleague, Dr. Burke, Kowdley supports screening:
"My stance is that there are ample data to suggest that patients identified early have normal life expectancy and can avoid all complications. Most patients identified via screening have early-stage treatable disease. It is unlikely that prospective controlled studies of the natural history of hemochromatosis (with no treatment) can be justified ethically. Treatment is easy, inexpensive and it works," he said.
"Should we be therapeutic nihilists (not believe in treatment) just because the current studies haven't satisfied all the requirements from a public health standpoint, especially when long- term natural history studies are unlikely to be done? If we identify a lot of people who have hemochromatosis but are unlikely to die from it, have we done them a disservice? In clinical medicine, sometimes we have to make do with the data available," Kowdley commented.
"To me, screening for hemochromatosis ... makes as much if not more sense than many other preventive health strategies such as mammography or PSA screening (for prostate cancer) and is less expensive. I am afraid that we will never be able to answer the questions required to receive universal support for screening. In the meantime, I am sure everyone will agree that there are ... patients developing end-organ damage that might have been prevented (by screening)," he concluded.
Consensus: Raise Awareness Now
Meanwhile, the American Medical Association (AMA) last year passed resolution 525 that supported the CDC guidelines on screening and indicated the resolve of the AMA to work with health agencies to inform people about iron overload.
After sifting through the issues relating to the screening question, one theme continually emerges. That is the need to raise the awareness about the problem. Everyone seems to agree that iron overload is underdiagnosed. Most doctors think of conditions other than hemochromatosis when they see someone complaining of unusual fatigue or joint pain. All of the physicians, researchers, and patient advocates interviewed by MedicineNet stressed the need for people to know about this disorder that is so common and yet unfamiliar.
But, of course, awareness of hemochromatosis will unfortunately not resolve the central question: To screen or not to screen?
For more, please vist the MedicineNet.com Hemochromatosis Center.