OFTEN UNDIAGNOSED GENETIC DISORDER CAN BE TREATED

Iron Overload Causes Fatal Symptoms

BY ANNE WILSON THE SALT LAKE TRIBUNE

Salt Lake County contractor Dan Monson was born with a genetic mutation that could have been easily treated with regular blood donations.

But Monson did not know until too late that he had hereditary hemochromatosis, a frequently undiagnosed genetic disorder that is much more common than AIDS, muscular dystrophy or multiple sclerosis.

The mutation that causes hemochromatosis prompts the body to absorb too much iron, which slowly damages the liver, heart, pancreas and sex glands. The potentially lethal condition can be easily diagnosed with a blood test and is simply treated by removing the stored iron with regular bloodletting, known as therapeutic phlebotomy.

But some people with the disorder are not diagnosed before they suffer major organ damage, because their symptoms are mild or suggestive of other diseases. Monson, who left behind a wife and 5-year-old son when he died in June at age 38, was one of them.

His wife, Carolyn Monson, said doctors were too quick to blame alcohol for the liver damage actually caused by excess iron.

``I feel like the doctors just labeled him as someone who drank too much alcohol and therefore deserved what he was getting,'' Monson said. ``That just seemed to be the attitude.''

Monson began feeling tired and having headaches in February. Then his hair started falling out. Tests showed he had cirrhosis, a liver disease linked to alcohol abuse. But the cause of the liver damage was not diagnosed until three days before Monson died, his wife said.

Lisa Rogers' hemochromatosis was missed, too, although the 35-year-old Salt Lake City scientist had been undergoing treatment for infertility, according to her mother, Juanita Taft Rogers, of Provo.

``They just screwed it all the way around,'' said Rogers of the medical care given her daughter, who died of heart failure on Sept. 15.

``If they had just discovered it, she could go give blood once a month. That would have taken care of it,'' Rogers said.

Hemochromatosis was once believed to be rare. But research in Utah and elsewhere indicates 1 in 200 people have both copies of a mutated gene that puts them at risk of absorbing too much iron.

Even more people -- 1 in 10 -- carry a single mutated gene, which usually does not cause disease. But if two carriers have children together, each of their offspring has a 1 in 4 chance of inheriting both mutated genes.

Iron is important to the metabolism of all cells, especially oxygen-carrying blood cells. Normally, the average male has about 4 grams of iron, the average female slightly less.

That amount remains constant, despite a daily western diet that contains 12 to 15 milligrams of iron, said James P. Kushner, professor of hematology at the University of Utah. The body absorbs only about 1 milligram of iron per day through the small intestine, to replace what is lost in sloughed cells.

But the gene that causes hemochromatosis doubles that amount. Once absorbed, the iron collects throughout the body, where it slowly accumulates and damages tissue. In men, that usually takes at least 40 years; most women are protected because they lose iron through menstruation and childbirth.

``The important point here is the only iron lost under normal circumstances is these sloughed cells . . . you don't pee it out, you don't sweat it out, you don't spit it out,'' Kushner said.

Kushner speculated the hemachromatosis mutation was advantageous during man's earlier history, when diets were more likely to be iron-deficient.

The gene that causes hemochromatosis was identified in July by Mercator Genetics, of Menlo Park, Calif. That means people can be screened for the mutation, but such screening is expensive, Kushner said.

As many as 1.5 million Americans have hereditary hemachromatosis but most do not know it, said Sharon McDonnell, a physician in the division of nutrition and physical activity at the Centers for Disease Control and Prevention.

``We've all been taught that it's a rare disease of white men and we're not looking for it,'' she said. ``We don't know how many people with the disorder go on to the really bad news.''

Some will be diagnosed after they develop symptoms: heart irregularities, chronic fatigue, cirrhosis, arthritis, impotence, infertility, early menopause, diabetes, darkened skin or abdominal pain. Others will die of diseases caused by iron overload although the underlying diagnosis is never made. University of Utah researchers who reviewed pathology reports of 15,000 liver biopsies found excess iron in 300 of the patients.

``We know now that many had hemochromatosis but it wasn't recognized,'' said the U.'s Kushner, who was involved in the study. The frequency of hereditary hemochromatosis, plus the fact that it can be easily detected and treated, has prompted the federal government to consider recommending widespread screening using an inexpensive blood test.

The CDC believes screening and early treatment of hemochromatosis ``represents a major chronic disease prevention opportunity.'' McDonnell said the agency will recommend that anyone over the age of 18 be screened during routine physicals for iron overload diseases, such as hemochromatosis.

A blood test that is not routinely done can accurately identify people who are storing too much iron. After being absorbed, iron binds with a protein called transferrin in the plasma, the liquid portion of blood. Measuring how much iron is joined to the transferrin -- transferrin saturation -- is used to diagnose iron overload.

But McDonnell said the agency wants to make sure the test is performed and interpreted the same way in all laboratories. And there are other concerns about screening:

-- People who have the double mutation for hemochromatosis, but do not have any disease from the excess iron, may have trouble getting health insurance.

-- The American Association of Blood Banks will not allow its members to accept blood from therapeutic phlebotomies because the donors have a disease and are not motivated solely by altruism. But if they are not allowed to donate the blood, people with hemochromatosis will have to pay for bloodletting.

McDonnell said many people with hemochromatosis, whether they are diagnosed or not, are already regular blood donors. Widespread screening would identify them and possibly have a significant impact on the nation's supply of donated blood.

``Hundreds of thousands of blood donors might be excluded,'' McDonnell said. But more research is needed to determine whether people with hemochromatosis can safely continue to donate. ``We need to do this in such a way that we don't make anybody's risk go up.''

The CDC, in cooperation with the U., other research institutions and patient groups, is conducting a national survey of people with hemochromatosis. The agency wants to know how patients were diagnosed and what effect the disease has had on their lives. To participate, contact the CDC at this toll-free number: 1-888-298-1436.

McDonnell said the survey will help doctors better define and diagnose the disease. ``By our lack of education as physicians and public health people, we are hurting people,'' she said. ``Having them speak to us about what they went through will be compelling.''