Hereditary Hemochromatosis

Causes of Hereditary Hemochromatosis

Although many people have never heard of hereditary hemochromatosis, it is not rare and affects as many as 1 in every 200 people in the United States, according to the Centers for Disease Control and Prevention (CDC).

Hereditary hemochromatosis is a genetic disorder caused by a mutation on a gene that regulates iron absorption — 1 in every 8 to 10 people in the United States carries a single copy of this defective gene, called HFE. Carriers don't necessarily have the condition themselves, but can pass the mutated gene on to their children.

Hereditary hemochromatosis is an autosomal recessive condition, which means that in order to get it, a child must inherit two mutated HFE genes — one from each parent. If a child inherits just one mutated HFE gene, the normal gene essentially balances out the defective HFE gene.

Even with two mutated genes, not everyone becomes ill. Although a majority of those with two mutated genes will eventually develop some type of iron overload, far fewer of them will absorb enough iron to develop serious problems.

In some cases, inheriting only one mutated gene may still eventually lead to iron overload, possibly affecting the heart, according to the Iron Disorders Institute. In these people, the iron overload may be triggered by a precipitating factor, such as hepatitis (inflammation of the liver) or alcohol abuse. Individuals with one mutated gene who become ill may also have mutations in other genes, yet to be discovered, that increase iron absorption.

Signs and Symptoms

Some people who test positive for hereditary hemochromatosis remain symptom-free for life. Kids who test positive rarely have any symptoms because iron takes years to accumulate.

Patients who do have symptoms may experience:

• muscle aches and joint pain, primarily in the fingers, knees, hips, and ankles; one of the earliest symptoms is arthritis of the knuckles of the first and second fingers
• chronic fatigue
• depression, disorientation, or memory problems
• stomach swelling, abdominal pain, diarrhea, or nausea
• loss of body hair, other than that on the scalp
• premature menopause
• gray or bronze skin similar to a suntan
• heart problems
• diabetes
• enlarged liver
• increased susceptibility to bacterial infections

With such a wide range of possible symptoms, the disease can be extremely difficult to diagnose. As symptoms progress, it's frequently misdiagnosed as chronic hepatitis, other forms of diabetes, Alzheimer's disease, iron deficiency, gallbladder illness, menstrual problems, thyroid conditions, or polycythemia (an increase in the number of red blood cells).

It's important to understand that someone with hereditary hemochromatosis can have some symptoms without having all of them (i.e., heart problems without skin color changes, diabetes, or liver problems).

Diagnosis and Screening

Luckily, the damage from hereditary hemochromatosis is completely preventable if it's diagnosed and treated early. Doctors may use these blood tests to measure the amount of iron in the blood and diagnose iron overload:

• serum ferritin measures the blood level of the protein that stores iron many places in the body
• serum iron measures iron concentrations in the blood
• total iron-binding capacity (TIBC) measures the amount of iron that can be carried in the blood

With these results, a transferrin saturation percentage (transferrin is a protein that carries iron in the blood) is calculated by dividing the TIBC into the serum iron. An elevated transferrin saturation percentage or serum ferritin level indicates iron overload.

Several gene mutations can cause hemochromatosis. A genetic test is available for the most common type of hemochromatosis, which accounts for about 85% of cases in the United States. However, only some of those who test positive will actually develop serious illness. The other 15% of individuals with symptomatic hemochromatosis will have mutations not in the HFE gene, but in other genes, which may be unknown or for which gene testing isn't routinely available.

Therefore, in cases in which high transferrin saturation and high serum ferritin are found but gene testing doesn't confirm hemochromatosis, a liver biopsy may be done to determine whether symptomatic hemochromatosis exists or is likely to develop.

Also, the doctor may recommend a DNA test to confirm hereditary hemochromatosis when a spouse or first-degree relative (parent, child, or sibling) has been diagnosed with it.

Given the prevalence of the condition, some specialists suggest screening to detect hereditary hemochromatosis before it causes problems. The following approaches to screening have been suggested:

• transferrin saturation testing on all adults at age 20, and every 5 years thereafter for anyone who has a family history of the condition (recommended by the College of American Pathologists)
• genetic screening for newborns to potentially benefit both the child and the rest of the family (proposed by the American Hemochromatosis Society)
• routine iron testing of all kids at age 4; those who have a genetic risk, but remain symptom-free, continue to be tested every 5 years thereafter

If you have a family history of hereditary hemochromatosis and are concerned about your child, talk to your doctor about screening tests.

Treatment

Besides specific treatment for complications of the condition — such as insulin for diabetes — most individuals with hereditary hemochromatosis are treated by regularly drawing blood, a process called phlebotomy that's similar to making a blood donation.

Initially, blood may be drawn once or twice weekly during the "de-ironing" phase until the level of iron in the body has dropped to normal. In many cases, it requires 2 or 3 years of periodic phlebotomy to reach the desired level.

After the de-ironing phase, when the serum ferritin level has fallen into the normal range, the patient usually remains on a maintenance schedule of three to four phlebotomy sessions a year. Doctors check ferritin levels annually to monitor iron accumulation. For most people, this treatment will continue for life.

Complications

When detected and treated early, any and all symptoms of hereditary hemochromatosis can be prevented, and the person can live a normal life. If left untreated, however, it can lead to damaging or even fatal iron overload.

Complications of untreated iron overload include: diabetes, arthritis, depression, impotence, hypogonadism (deficient production of sex hormones by the testicles or ovaries), gallbladder disease, cirrhosis (disease and scarring of the liver), heart attack, cancer, and failure of other organs.

Caring for Your Child

Treatment for kids typically isn't as aggressive as for adults, and making some minor dietary changes can help slow iron accumulation.

Talk to your doctor about taking steps to delay or reduce iron overload. You might:

• Limit red meat in your child's diet. Iron-rich vegetables are fine because the body doesn't absorb iron from plant sources very well.
• Include moderate amounts of black, green, or oolong tea in your child's diet. The tannin from tea helps minimize iron absorption (note: herbal tea doesn't contain tannin).
• Avoid breakfast cereals, breads, and snacks that are enriched with iron.
• Ensure your child is immunized against hepatitis A and B.
• Limit vitamin C supplements to less than 100 milligrams per day, because vitamin C enhances iron absorption.
• Use a children's multivitamin that doesn't contain iron.
• Avoid raw shellfish, which occasionally can be contaminated with bacteria that might be harmful to someone with an iron overload.

These simple steps can help ensure that your child will remain free of symptoms of the disease.

Reviewed by: Christopher N. Frantz, MD
Date reviewed: October 2010