Hemochromatosis

From the Mayo Clinic:

Introduction
Of all the minerals you need for good health, iron is one of the most familiar. After all, the producers of everything from breakfast cereals to vitamin tonics tell us that iron builds rich, red blood. Iron does help form oxygen-carrying hemoglobin in your red blood cells, but it's also essential for a number of other body processes, including proper brain function, a strong immune system and healthy muscles. Yet for people with hereditary hemochromatosis (HH), even small amounts of iron can cause serious problems.

That's because hereditary hemochromatosis causes your body to absorb too much iron from the food you eat. The excess is stored in your organs, especially your liver, heart and pancreas. Sometimes the stored iron damages these organs, leading to life-threatening conditions such as cancer, heart problems and liver disease.

Signs and symptoms of hereditary hemochromatosis usually appear in midlife, although they may occur earlier. The most common complaint is joint pain, but hereditary hemochromatosis can also cause a number of other symptoms, including fatigue, abdominal pain and impotence. Though not always easy to diagnose, hereditary hemochromatosis can be effectively treated by removing blood from your body to lower the level of iron.

Signs and symptoms
Although the genetic defect that causes hemochromatosis is present at birth, most people don't experience signs and symptoms until later in life — usually between the ages of 30 and 50 in men and after age 50 in women. Women are more likely to have symptoms after menopause, when they no longer lose iron with menstruation and pregnancy.

Some people with hemochromatosis never have symptoms. Others experience a wide range of problems. These can vary considerably from person to person and may be different for men and women. In addition, early signs and symptoms of hemochromatosis mimic those of many other common conditions, making hemochromatosis difficult to diagnose. Signs and symptoms include:

Arthritis, especially in your hands
Chronic fatigue
Loss of sex drive (libido) or impotence
Lack of normal menstruation (amenorrhea)
Abdominal pain
High blood sugar levels
Low thyroid function (hypothyroidism)
Abnormal liver function tests, even if no other symptoms are present
In advanced stages of the disease, you may develop serious conditions such as:

Cirrhosis — a condition marked by irreversible scarring of the liver
Liver failure
Liver cancer
Diabetes
Congestive heart failure
Cardiac arrhythmia
Some people with advanced hemochromatosis develop a bronze color to their skin when iron deposits in the skin cells produce excess melanin — the pigment that gives skin its normal color. Visible iron deposits can also make skin appear gray.

Causes
Iron plays an essential role in the formation of hemoglobin — a protein in red blood cells that transports oxygen from your lungs to all the tissues of your body — and of myoglobin, a form of hemoglobin in your muscles. Iron is also necessary for energy production and a strong immune system and is a component of many important enzymes.

You normally consume about 10 milligrams (mg) of iron every day in the food you eat. Of that, your body absorbs about 1 mg, or 10 percent of the iron you ingest. Most of this is stored in the hemoglobin, but a small amount is stored in your bone marrow, spleen and liver. When these stores are adequate, your body reduces the amount of iron absorbed by your intestine so that you don't accumulate excess amounts.

But if you have hemochromatosis, you may absorb as much as 20 percent of the iron you ingest. Because your body can't use or eliminate this extra iron, it's stored in the tissues of major organs, especially your liver. Eventually you may accumulate five to 20 times as much iron as normal. Over a period of years, the stored iron can severely damage many organs, leading to organ failure and chronic diseases such as cirrhosis and diabetes.

Although excess iron (iron overload) is a common problem, it's not always the result of hemochromatosis. Several factors, including frequent blood transfusions, high amounts of dietary iron and certain types of anemia, can cause excess iron in your body. People with chronic liver disease may also have increased iron levels. But in the United States, hemochromatosis is the most frequent cause of high blood iron levels.

The genetics of hemochromatosis
You have approximately 30,000 genes — information centers in your cells that control your body's growth, development and function. A mutation in just one gene can drastically alter the way your body works.

The gene that controls the amount of iron you absorb from food is called HFE. The HFE gene has two common mutations, C282Y and H63D. In the United States, most people with hemochromatosis have inherited two copies of C282Y — one from each parent.

Inheriting just one gene with the C282Y mutation means you're a carrier. You aren't likely to develop the disease yourself, although you may absorb more iron than normal. About one in every 10 Caucasians carries one gene for hemochromatosis. If both your parents are carriers, you have a 25 percent chance of inheriting two mutated genes.

A few people inherit one copy of C282Y and one of H63D. Of these, a small percentage develop symptoms of hemochromatosis. An even smaller number of people inherit two copies of H63D. Whether they're at risk of hemochromatosis is a matter of debate.

Complicating matters further, not everyone with two C282Y gene mutations develops problems with iron overload. Experts aren't sure of the exact number of people who do, and it's not possible to determine who will experience symptoms and who won't.

In addition, researchers continue to discover new proteins and genes that are responsible for rare cases of iron overload and that may lead to symptoms in people with HFE-related disease.