Hemochromatosis

According to the National Heart, Lung and Blood Institute, not everyone who has hemochromatosis will have signs and symptoms, and though estimates vary, as many as half of those with the disease may not have any initial symptoms. Signs and symptoms tend to emerge and increase in severity over a long period of time and can be similar to those of other conditions.

Typically, men will not become symptomatic until they are 40-60 years old. Most women with hemochromatosis will not experience symptoms until several years after their menstrual periods stop due to menopause (around age 50).

Signs and symptoms will vary from person to person and may include:

• Fatigue, weakness
• Abdominal pain
• Joint pain
• Increased blood glucose levels and diabetes
• Liver dysfunction and/or abnormal liver blood tests
• Decreased sex drive, erectile dysfunction in men
• Lack of menstruation in women
• Low thyroid hormone (hypothyroidism)
• Changes in skin color, turning grey or bronze

The tests below are used to detect and diagnose hemochromatosis and evaluate body organs for the severity of iron overload. They may also be used to monitor the effectiveness of treatment. Genetic testing may be used to confirm a diagnosis, but since many people who have genetic mutations associated with the disease never develop symptoms, blood tests are considered the most reliable form of diagnosis.

Laboratory tests

Laboratory testing typically includes:

• Serum iron — used to check iron levels in the blood
• Total iron-binding capacity (TIBC) — measures the total amount of iron that can be bound by proteins in the blood; transferrin is the primary iron-binding protein and the TIBC test is a good indirect measurement of transferrin availability.
• Transferrin saturation — a calculation using the iron and TIBC test results, representing the percentage of the transferrin that is saturated with iron; it is elevated with hereditary hemochromatosis (HH) but is not specific for it.
• Ferritin — used to evaluate the body’s iron stores; it may be elevated with HH but is not specific for it. In those who have HH gene mutations, normal levels mean low risk for developing organ damage.
• Liver panel — a group of tests used to evaluate liver function
• Genetic testing — can be used to help confirm a diagnosis of HH. Most cases of HH, about 80-90%, are caused by two copies of a C282Y mutation in the HFE gene. The presence of two copies of the C282Y mutation does not necessarily mean that a person will develop the disorder but does indicate an increased risk, and men are more likely to be affected than women. The largest population study found about a 25% risk among men and 1% risk among women. Sometimes two copies of H63D or S65C mutations of the HFE gene or paired combinations of the three may cause HH. Rarely, the condition may be due to another genetic abnormality.
• Liver biopsy — while it is usually not necessary to confirm the diagnosis by examination of a liver biopsy specimen for iron accumulation, a biopsy is often done to help determine the extent of liver damage.

Non-laboratory tests
An MRI (magnetic resonance imaging) test may be used to help evaluate the amount of iron in the liver.

The goals of hemochromatosis treatment are to reduce the amount of iron in the body and maintain it at near normal levels, to minimize permanent organ damage, and to address complications. If a person has secondary hemochromatosis, then treatment should also address the underlying disorder or condition. Because not all individuals who have the genetic changes need treatment, only those who have organ damage from excess iron are generally treated.

Hemochromatosis is usually treated with phlebotomy therapy, which typically involves the removal of a unit of blood. The frequency and length of treatment depend on the cause and degree of iron overload; for example, in those with severe iron overload, phlebotomy may initially be done once or twice a week, but after the excess iron is removed, phlebotomy may only be done a few times a year.

There is no cure for hereditary hemochromatosis, but it can be successfully managed over a person’s lifetime.

Someone who has secondary hemochromatosis may not require long-term blood removal treatment if the underlying condition can be resolved–and if their iron overload is due to many transfusions, it may not be possible to do phlebotomy if the need for transfusions is still present. There are also drugs that bind iron and allow it to be eliminated in the urine, (iron chelation drugs) and drugs that reduce gastric acid production (proton pump inhibitors) that reduce the amount of iron in food that is absorbed. These may be used for people who cannot safely have phlebotomy performed.

The U.S. Food and Drug Administration has approved the use of blood from hemochromatosis patients as donor blood. For a list of locations where hemochromatosis patients can go to donate their blood, visit the American Hemochromatosis Society’s web page on this subject.

The following lists possible gene combinations for the HFE gene:

• Two copies of C282Y or a copy of C282Y together with a copy of H63D or S65C mutant genes places a person at the highest risk for Hereditary hemochromatosis.
• Two copies of H63D, S65C, or one copy each of H63D and S65C puts a person in the low risk category and is only rarely associated with HH.
• A single copy of C282Y, H63D or S65C means that the person is a carrier. Carriers do not develop the disease, but they can pass it on to their offspring if they have children with someone who is also a carrier.

Of course, other genes besides the HFE gene can affect a person’s ability to metabolize iron, so no combination of genes guarantees that someone will or will not develop the disease. For example, it is estimated that only about 25% of men and about 1% of women who have two copies of the C282Y mutation will ever develop organ damage related to excess iron.

Hereditary hemochromatosis affects more men than women, and symptoms of the disorder emerge at an earlier age for men, typically at about 30 to 50 years old. Two other rare forms of inherited hemochromatosis, neonatal and juvenile hemochromatosis, can cause severe iron overload in children and young adults. These disorders are caused by mutations in a different gene, one called HJV that causes changes in a protein called hemojuvelin that also affects iron metabolism. In fact, a small percentage of cases of HH are due to mutations in genes coding for other proteins that affect iron metabolism, including hemojuvelin as well as transferrin-receptor 2, ferroportin and hepcidin. Tests for these mutations are not widely available, however.