Testing for Iron Overload Disease: Hemochromatosis

If you're reading this blog, chances are you or someone you know has already been diagnosed with an iron overload disease, such as hemochromatosis, sickle cell anemia, African siderosis, beta-thalassemia, porphyria, or juvenile hemochromatosis. The diagnosis of iron overload disease, however, is not based solely on the amount of iron in the blood. Let's take a look at how testing for iron overload works.

The first number to look at in determining whether someone has an iron overload is, as you might expect, serum iron. The term "serum" refers to the blood. Most of the body's stores of iron do not circulate in a form measured by this test. About 65 per cent of the body's total iron supply is used to make hemoglobin, the oxygen transport molecule found in red blood cells. About 30 per cent of the body's iron is stored in the liver, spleen, and bone marrow, for use in future manufacture of red blood cells. Another 4 per cent is found in the myoglobin, the oxygen "grabbing" molecule that allows muscles to operate with oxygen even when bloodstream oxygen levels are low.

This leaves only 1 per cent of the body's iron in a form that lab tests usually measure. This 1 per cent is bound to a transporter molecule called transferrin. The serum iron test measures the amount of iron bound to transferrin in the bloodstream. The concentrations of iron measured by the test are extremely low. Healthy levels of serum iron range from 60 to 170 millionths of a gram (micrograms) per deciliter of blood.

Hemochromatosis, beta-thalassemia, and other iron overload conditions, however, are not just about how much iron is in the blood. One reason is that the amount of iron in the bloodstream is variable. It's greater after eating foods that contain iron. That is the reason this test requires fasting. For women, it's lower after menstrual bleeding. Iron levels are increased by use of the contraceptive Pill, estrogen, or L-dopa. Iron levels are decreases by use of testosterone, drugs for gout, and the antibiotic methicillin.

And the major concern in iron overload is not just how much iron there is in the blood, but whether there is any excess capacity for transporting it where it needs to go. That is why doctors usually also order tests for serum ferritin and total iron binding capacity.

Ferritin is the "ferry" that transports iron in the bloodstream. Each molecule of ferritin can transport up to 4,500 iron atoms. Ferritin levels go up when there's cancer or infection, and also in iron overload disease. Total iron binding capacity (TIBC) measures the percentage of ferritin that is carrying iron. In healthy people, TIBC numbers range from 25 to 35 per cent. In iron overload disease, the TIBC numbers range from 45 per cent and up. Treatment to relieve iron overload, to ensure the bloodstream can still handle all the iron in circulation.

A liver biopsy used to be part of the diagnosis of iron overload disease. At least in the case of hemochromatosis, it not longer is. Taking out a minute sample of liver tissue to examine for excessive iron stores is an excellent way to find out if iron overload disease has already caused liver damage such as cirrhosis or liver cancer. It is not necessary for determining if the iron overload is caused by hemochromatosis.

Most people who have hemochromatosis carry two copies of a gene called C282Y. Some people who have hemochromatosis have one C282Y gene with another gene called H63D, and they usually have a much milder form of the disease. If you have these genes, and you have a TIBC over 45 per cent, you are assumed to have hemochromatosis.

Generally speaking, people with the genes for hemochromatosis who are under the age of 40 and who have ferritin levels under 1000 nanograms (billionths of a gram) per deciliter of blood are at very little risk for having already developed cirrhosis of the liver. People over the age of 40 who have the genes for hemochromatosis and ferritin levels over 1000 ng/dl are considered at high risk for developing cirrhosis of the liver and other symptoms, and are offered phlebotomy (blood withdrawal) or an iron chelating drug such as ExJade (deferasirox).

In future weeks, I'll have much more detailed information about the ways doctors diagnose other the other iron overload diseases. Remember, this blog is not itself a tool of diagnosis. Always discuss lab results with your doctor.