Hemochromatosis (HE-muh-IRO-muh-TOE-sis), also called iron overload disease, is a disorder in which too much iron is absorbed from food and builds up in the body. Hemochromatosis is usually an inherited disorder.
Iron is an essential mineral obtained from food. The human body normally absorbs about 10 percent of the iron in food. People with hemochromatosis absorb excess iron, up to as much as 30 percent of the iron they ingest. Because the body does not have a mechanism for removing the excess iron, it is stored in tissues, particularly in the skin, liver * , heart, pancreas * , and joints. The iron can damage these organs and, without treatment, eventually cause them to fail, possibly leading to death.
Most of the iron in the body is contained in hemoglobin * molecules in red blood cells, where it is responsible for transporting oxygen to body tissues. Iron is also required to store oxygen in muscles as myoglobin and to make DNA * . But excess iron can be a deadly poison. Because of this, the body has an elaborate system for ensuring that only the correct amount of iron is absorbed.
In normal iron metabolism * , iron ingested in food is taken up by cells called enterocytes * in the duodenum * of the small intestine * . The amount of iron that enterocytes absorb depends on the type of iron. Food contains two types: heme and nonheme iron. Most heme iron comes from the hemoglobin and myoglobin in meat, poultry, and fish. Nonheme iron is found in legumes, fruits, cereals, and vegetables. It is easier for the body to absorb heme iron. Indeed, 15 to 35 percent of heme iron gets absorbed, compared to 2 to 20 percent of nonheme iron. Once enterocytes absorb iron, they can keep the iron in ferritin * molecules or send it to the bloodstream for use in the body. Most iron binds to the ferritin inside enterocytes, which live for five to six days. When enterocytes die, they are sloughed off to be excreted in feces * , along with the iron they contain. The amount of iron released into the bloodstream depends on how much iron the body needs. This iron travels in a protein called ferroportin. In the blood, the iron then binds to a protein called transferrin, which carries it where it is needed. Transferrin is normally 25 to 35 percent saturated (filled) with iron. If the transferrin is too heavily loaded, it loses its ability to bind iron, resulting in free iron in the blood. Reactions with free iron produce chemicals called free radicals that are very destructive to cells and tissues. In addition, free iron can nourish bacteria that are normally harmless but can cause life-threatening infections in people with high iron levels. Cancer cells also thrive on iron.
There are two main types and several subtypes of hemochromatosis. Primary or hereditary hemochromatosis is caused by mutations * in genes * that code for the proteins involved in regulating the absorption, transport, and storage of iron in the body. Primary hemochromatosis is categorized according to the age of onset, the genetic * cause, and the mode of inheritance.
Type 1 hemochromatosis is one of the most common inherited disorders in the United States, affecting about 1 million people. This form of hemochromatosis mainly affects Caucasians of Northern European ancestry and is extremely rare in African Americans, Hispanics, Asian Americans, and Native Americans.
People are born with the genetic mutations that cause type 1 hemochromatosis, but symptoms may not appear for many decades. Symptoms in men usually start between the ages of 40 and 60. Symptoms in affected women usually do not begin until menopause * occurs. This is because premenopausal women lose iron through menstruation * and pregnancy, thereby preventing iron overload.
Type 1 hemochromatosis is caused by mutations in the hemochromatosis gene (called HFE), which encodes a protein called hemochromatosis protein. This protein is located on the surface of intestinal and liver cells, as well as on some immune system * cells. It regulates how much iron these cells take up from circulating transferrin. It also helps control production of the hormone hepcidin by the liver. Hepcidin inhibits ferroportin, thereby reducing the amount of iron that enterocytes release into the bloodstream. Hepcidin is therefore important in preventing iron overload in body cells. More than 20 different HFE gene mutations that cause type 1 hemochromatosis have been identified. The most common mutation prevents the HFE protein from reaching cell surfaces.
Experts believe that about 10 percent of Americans carry at least one copy of a mutated HFE gene. But only people with two defective copies of HFE—one inherited from each parent—are likely to develop type 1 hemochromatosis. However, doctors estimate that only about half of those with two mutated HFE genes will actually develop symptoms, even though these individuals will pass one defective gene to their offspring.
Symptoms of type 3 hemochromatosis are usually evident by age 30 in individuals with two defective copies of the transferrin receptor 2 (TFR2) gene, which codes for TFR2 protein. This protein senses transferrin levels and also plays a role in signaling liver cells to produce hepcidin. Scientists have discovered at least nine TFR2 mutations that cause type 3 hemochromatosis. Some mutations inhibit the production of TFR2 protein. Others result in abnormal, nonfunctional TFR2 protein. All these mutations ultimately affect transferrin's ability to regulate iron binding to cell receptors * and inhibit hepcidin production.
Medical experts used to characterize another rare form of hemochromatosis known as neonatal * hemochromatosis as a subtype of the hereditary form of the disease. But research that was first reported in 2007 indicates that this form of the illness actually represents a third main category of hemochromatosis. In neonatal hemochromatosis, iron accumulation begins before birth, and some affected fetuses and newborns suffer liver failure and die before or shortly after birth. Researchers believe the mother's immune system may produce antibodies * that damage the fetus's liver, but this has not been proved.
Secondary hemochromatosis is iron overload caused by some other disease or condition. These include:
Many people with hemochromatosis never experience symptoms or complications, despite having high levels of iron in their bodies. In some cases, this is because an individual's eating habits or tendency to donate blood frequently may be lowering his or her iron levels. Other people suffer from serious complications and may die of the disease.
Early symptoms of hemochromatosis are nonspecific and may include the following:
Later symptoms of hemochromatosis may include:
The decreased secretion or absence of sex hormones caused by type 2 hemochromatosis becomes evident during adolescence. Females usually begin menstruation normally, but menses cease after a few years. Male puberty * may be delayed or symptoms of sex-hormone deficiency, such as impotence * , become evident. If left untreated, type 2 hemochromatosis often leads to heart disease * by age 30.
Hemochromatosis is diagnosed by a physical exam, medical and family histories, and several laboratory tests. First, a physician will rule out dietary causes for symptoms, such as iron supplements or large quantities of vitamin C supplements. Vitamin C increases iron absorption and can thus lead to iron overload.
The most commonly performed diagnostic tests include:
Since the liver is the most commonly affected organ, doctors usually assess liver damage with one or more of the following:
Early diagnosis and treatment can prevent, delay, and sometimes even reverse the complications of hemochromatosis. The goals of treatment are to:
The most common treatment for hemochromatosis is therapeutic phlebotomy, in which blood is periodically withdrawn through a vein * . Treatment usually begins shortly after diagnosis. For most patients, about a pint of blood is withdrawn one to two times per week for about a year. Once iron levels stabilize at a safe level, many patients only require phlebotomy several times per year for the rest of their lives. While phlebotomy is the standard hemochromatosis treatment, some patients undergo a newer procedure called erythrocytapheresis * . A study by Dutch researchers that was published in 2016 found that 80 percent of the patients surveyed preferred erythrocytapheresis over phlebotomy because they needed fewer treatments each year. However, erythrocytapheresis is not widely used, in part because it is more expensive.
People who cannot undergo periodic phlebotomy may be treated with iron chelation therapy. This involves administering oral or injected medications that bind to iron and remove it from the body in the urine or feces.
Hemochromatosis is also treated with dietary measures, including:
Even though there is no way to prevent hemochromatosis in genetically susceptible people, these individuals can control certain environmental and lifestyle factors that may affect the onset and progression of symptoms. These factors include:
Books and Articles
Catalase, Ralph. Living Well with Hemochromatosis: A Handbook on Diet, Iron Overload Treatments and Protective Supplements. CreateSpace, 2013.
MedlinePlus. “Hemochromatosis.” U.S. National Library of Medicine. https://www.nlm.nih.gov/medlineplus/hemochromatosis.html (accessed June 6, 2016).
National Institute of Diabetes and Digestive and Kidney Diseases. “Hemochromatosis.” (accessed March 6, 2016).
American Hemochromatosis Society. PO Box 950871, Lake Mary, FL 32795-0871. Telephone: 407-829-4488. Website: http://www.americanhs.org (accessed March 6, 2016).
Centers for Disease Control and Prevention. 1600 Clifton Road, Atlanta, GA 30329-4027. Toll-free: 800-232-4636. Website: http://www.cdc.gov (accessed March 6, 2016).
National Heart, Lung, and Blood Institute. PO Box 30105, Bethesda, MD 20824-0105. Telephone: 301-592-8573. Website: http://www.nhlbi.nih.gov (accessed March 6, 2016).
* liver is a large organ located beneath the ribs on the right side of the body.
* pancreas (PAN-kree-us) is a gland located behind the stomach that produces enzymes and hormones necessary for digestion and metabolism.
* hemoglobin (HE-muh-glo-bin) is the oxygen-carrying pigment of the red blood cells.
* DNA, or deoxyribonucleic acid (dee-OX-see-ry-bo-noo-klay-ik), is the twisted-ladder-shaped chemical substance that contains the genetic code necessary to build and maintain the structures and functions of living organisms.
* metabolism (meh-TAB-o-liz-um) is the process in the body that converts foods into the energy necessary for body functions.
* enterocytes (en-TARE-o-sites) are cells in the lining of the small intestine that absorb nutrients from food and send these nutrients into the bloodstream.
* duodenum (do-oh-DEEN-um) is the top section of the small intestine. The breakdown and absorption of nutrients begins in the duodenum.
* small intestine is the part of the intestines that directly receives food as it leaves the stomach.
* ferritin (FERR-ih-tin) is a protein in cells that binds to, stores, and releases iron.
* feces (FEE-seez) is the excreted waste from the gastrointestinal tract.
* insulin is a hormone produced by beta cells in the pancreas. It is crucial in controlling the level of glucose (sugar) in the blood and in helping the body use glucose to produce energy.
* diabetes (dye-uh-BEE-teez) is a condition in which the body's pancreas does not produce enough insulin or the body cannot use the insulin it makes effectively, resulting in increased levels of sugar in the blood.
* mutations (mu-TAY-shuns) are changes in a chromosome or a gene.
* genes (JEENS) are the parts of DNA molecules that carry hereditary information.
* genetic (juh-NEH-tik) refers to heredity and the ways in which genes control the development and maintenance of organisms.
* menopause (MEN-oh-pawz) is the end of menstruation.
* menstruation (men-stroo-AYshun) is the discharge of the blood-enriched lining of the uterus. Menstruation normally occurs in females who are physically mature enough to bear children. Menstruation ceases during pregnancy and with the onset of menopause.
* immune system (im-YOON SIStem) is the body's defense system. It is composed of various types of white blood cells and the substances they produce to protect the body from germs, cancers, and other harmful invaders.
* receptors are structures on cell membranes that bind to a specific substance, such as iron, and allow the substance to enter the cell.
* neonatal (nee-o-NAY-tal) refers to the first four weeks after birth.
* antibodies (AN-teh-bah-deez) are chemicals produced by immune cells that target specific substances known as antigens. Usually, antibodies target foreign substances or microorganisms that enter the body. But sometimes immune cells produce antibodies that target and destroy other body cells.
* anemia (uh-NEE-me-uh) is a condition in which there is decreased hemoglobin in the blood and, usually, fewer than normal numbers of red blood cells.
* hepatitis (heh-puh-TIE-tis) is inflammation of the liver. Hepatitis can be caused by viruses, bacteria, and a number of noninfectious medical conditions.
* dialysis (dye-AL-uh-sis) is a process that removes waste, toxins (poisons), and extra fluid from the blood. Usually dialysis is done when a person's kidneys are unable to perform these functions normally.
* arthritis (ar-THRY-tis) refers to any of several disorders characterized by inflammation of the joints.
* cirrhosis (sir-O-sis) is a condition that affects the liver, involving long-term inflammation and scarring, which can lead to problems with liver function.
* pituitary (pih-TOO-ih-tare-e) is a small oval-shaped gland at the base of the skull that produces several hormones that affect various body functions, including growth.
* thyroid gland (THYE-roid GLAND) is located in the lower part of the front of the neck. The thyroid produces hormones that regulate the body's metabolism (meh-TAB-o-liz-um).
* adrenal glands (a-DREEN-al glands) are the pair of glands located above the kidneys that produce a variety of hormones, including adrenaline and steroids.
* puberty (PEW-burr-tee) is the period during which sexual maturity is attained.
* impotence (IMM-po-tense) is a condition in which a male cannot achieve or sustain an erection.
* heart disease is a broad term that covers many conditions that prevent the heart from working properly to pump blood throughout the body.
* MRI is short for magnetic resonance imaging, which produces computerized images of internal body tissues using magnets and radio waves.
* biopsy (BI-op-see) is a test in which a small sample of body tissue is removed and examined for signs of disease.
* vein is a vessel that carries blood to the heart. Veins have greater capacity and thinner walls than arteries and contain valves that prevent blood from flowing backward and away from the heart.
* erythrocytapheresis (eh-RITHrow- sigh-tah-ferr-ee-sis) involves withdrawing blood from a patient's body, sending the blood to a machine that separates the red blood cells from whole blood, and returning the blood (minus its red blood cells) to the patient.