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The dangers of too much iron

Those with a common genetic condition have to watch their iron level

Published: May 2013

During your next game of medical trivia, ask this question: "What’s the most common genetic disease of white men?" If all you do is draw blank stares, give these clinical vignettes as clues.

  • An apparently healthy 50-year-old man has a father who died of cirrhosis of the liver, even though he was a nondrinker.
  • A 45-year-old man has severe heart failure, even though his coronary arteries are clear and heart valves are normal.
  • A 57-year-old man develops diabetes and has a year-round tan, even though he seldom out in the sun.

The answer: hemochromatosis. And in case they continue to have a quizzical look on their faces, you can add, "You know, iron-overload disease."

Hemochromatosis was for many years thought to be a rare genetic disorder. But today we know that it results from the inheritance of an abnormal recessive gene from each parent. One in every 150 to 250 white people is affected, research shows. It’s less common among blacks and practically nonexistent among Asians. The disease rarely shows up before people are in their 40s or 50s, and men are 24 times more likely to have complications from it than women.

The defective gene causes the decreased production of hepcidin, a liver protein that prevents the intestinal absorption of excess dietary iron. Other than menstruating women, most people need very little iron in their diets to balance out our losses. Were it not for that hepcidin-mounted defense, we would all be at risk for iron overload just from dietary sources. And, when too much iron is absorbed, it can infiltrate and eventually destroy almost every major organ in the body.

Serious complications abound

People who don’t make enough hepcidin have no such protection, yet only about 10 percent will ever develop symptoms, for reasons still not understood. And in those who do, not all organs are involved at the same time or to the same extent. The liver is most commonly affected, with cirrhosis (scarring) and liver failure the ultimate result. About 6 percent of those with cirrhosis develop liver cancer. A timely liver transplant offers the only chance for survival. In order to avoid the fate of his father, the first man described above is currently getting the standard treatment for hemochromatosis, which involves periodic phlebotomy (bloodletting) to get rid of some of the excess iron.

When the heart is affected, as in the second vignette, the result can be cardiomyopathy (the replacement of the heart muscle with scar tissue), heart block, and serious abnormal heart rhythms. The cardiomyopathy is often resistant to treatment, and cardiac transplantation can be lifesaving. Infiltration of the pancreas with iron destroys insulin-producing cells and causes secondary diabetes, and, when skin is involved, as in our third example, imparts a distinctive coloration sometimes described as "bronze diabetes." The endocrine system, including pituitary, thyroid, and testicles, suffers as well, with impotence and other deficiencies as the result.

Who needs testing?

The laboratory markers for hemochromatosis are relatively inexpensive blood tests. Elevation of serum ferritin, the protein that stores iron, can be the best indicator of increased iron. If tests show that transferrin, the protein that transports iron through the bloodstream, is saturated with iron, that virtually clinches the diagnosis. Gene testing should also be done before committing anyone to periodic phlebotomies for an indefinite period of time.

Despite the frequency of the disease, not everyone needs to be screened. Experts disagree about who will and who won’t develop symptoms, and the large racial disparities in disease prevalence argue against screening everyone. But targeted screening of people with certain risk factors and symptoms makes good sense. Ask your doctor about testing if you have one or more of the following:

  • A family history of hemochromatosis.
  • A close family member with nonalcoholic cirrhosis of the liver, cardiomyopathy, or primary liver cancer.
  • Unexplained abnormal liver-function tests.
  • Cardiomyopathy, heart block, or abnormal heart rhythms.
  • Adult-onset diabetes mellitus that requires insulin treatment.
  • Impotence traceable to an endocrine cause. 

Marvin Lipman, M.D.

Chief Medical Adviser and Medical Editor
Editor's Note:

A version of this article first appeared in the monthly newsletter Consumer Reports on Health. 



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