Hemochromatosis is an inherited blood disorder that causes the body to retain excessive amounts of iron. This iron overload can lead to serious health consequences, most notably cirrhosis of the liver.
Hemochromatosis is also known as iron overload, bronze diabetes, hereditary hemochromatosis, and familial hemochromatosis. The inherited disorder causes increased absorption of intestinal iron, well beyond that needed to replace the body's loss of iron. Iron overload diseases afflict as many as 1.5 million persons in the United States. The most common of these, as well as one of the most common genetic disorders in the United States, is hereditary hemochromatosis. Men and women are equally affected by hemochromatosis, but women are diagnosed later in life because of blood loss from menstruation and childbirth. It most commonly appears in patients between the ages of 40 to 60 years, since it takes many years for the body to accumulate excessive iron. Symptoms appear later in females than in males—usually after menopause.
Hemochromatosis causes excess iron storage in several organs of the body including the liver, pancreas, endocrine glands, heart, skin, joints, and intestinal lining. The buildup of iron in these organs can lead to serious complications, including heart failure, liver cancer, and cirrhosis of the liver. It is estimated that about 5% of cirrhosis cases are caused by hereditary hemochromatosis.
Idiopathic pulmonary hemosiderosis, a disorder afflicting children and young adults, is a similar overload disorder characterized by abnormal accumulation of hemosiderin. Hemosiderin is a protein found in most tissues, especially the liver. It is produced by digestion of hematin, an iron-related substance.
Hereditary hemochromatosis is an autosomal recessive condition. This means that individuals with hemochromatosis have inherited an altered (mutated) gene from both of their parents. Affected individuals have two abnormal hemochromatosis genes and no normal hemochromatosis gene.
The gene that causes hemochromatosis has been identified, and the most common abnormalities of the gene have been described. The gene is on chromosome 6; it is called HFE. Scientists have not confirmed the function of the normal gene product; they do know that it
Because it is an autosomal recessive condition, siblings of individuals who have hemochromatosis are at a 25% risk to also be affected. However, the likelihood that an individual will develop symptoms depends on which gene mutation he or she has as well as environmental factors. The two most common changes in the HFE gene are C282Y and H63D. The age at which symptoms begin is variable, even within the same family.
Hemochromatosis is one of the most common genetic disorders in the United States. Approximately one in nine individuals have one abnormal hemochromatosis gene (11% of the population). Since everyone has two copies of each gene, these individuals have an abnormal HFE gene and a normal gene. They are called carriers. Between 1/200 and 1/400 individuals have two abnormal genes for hemochromatosis and no normal gene.
With most autosomal recessive conditions, an affected person's parents are carriers. If more than one family member has the condition, they are siblings. Hemochromatosis is so common, however, that families are seen in which both parents are affected, or one parent is affected and the other parent is a carrier. More than one generation may be affected, which is not usually seen in rare autosomal recessive conditions.
Signs and symptoms
The symptoms of hemochromatosis include fatigue, weight loss, weakness, shortness of breath, heart palpitations, chronic abdominal pain, and impaired sexual performance. The patient may also show symptoms commonly connected with heart failure, diabetes or cirrhosis of the liver. Changes in the pigment of the skin may appear, such as grayness in certain areas, or a tanned or yellow (jaundice) appearance. The age of onset and initial symptoms vary.
Idiopathic pulmonary hemosiderosis may first, and only, appear as paleness of the skin. Sometimes, the patient will experience spitting of blood from the lungs or bronchial tubes.
The most common diagnostic methods for hemochromatosis are blood studies of iron, genetic blood studies, magnetic resonance imaging (MRI), and liver biopsy. Blood studies of transferrin–iron saturation and ferritin concentration are often used to screen for iron overload. Ferritin is a protein that transports iron and liver enzymes. Additional studies are performed to confirm the diagnosis.
Blood studies used to confirm the diagnosis include additional iron studies and/or genetic blood studies. Genetic blood studies became available in the late 1990s. Genetic testing is a reliable method of diagnosis. However, in 2001 scientists and physicians studied how accurately having a hemochromatosis mutation predicts whether a person will develop symptoms. Most individuals affected with hemochromatosis (87%) have two identifiable gene mutations, so genetic testing will confirm the diagnosis. Genetic studies are also used to determine whether the affected person's family members are at risk for hemochromatosis. The results of genetic testing are the same whether or not a person has developed symptoms.
MRI scans and/or liver biopsy may be necessary to confirm the diagnosis. MRI studies of the liver (or other iron-absorbing organs), with quantitative assessment of iron concentration, may reveal abnormal iron deposits. For the liver biopsy, a thin needle is inserted into the liver while the patient is under local anesthesia. The needle will extract a small amount of liver tissue, which can be analyzed microscopically to measure its iron content and other signs of hemochromatosis. Diagnosis of idiopathic pulmonary hemosiderosis begins with blood tests and xray studies of the chest.
Treatment and management
Patients who show signs of iron overload will often be treated with phlebotomy. Phlebotomy is a procedure
Diet restrictions may help lower the amount of iron in the body, but do not prevent or treat hemochromatosis. Individuals who are affected or who know they have two C282Y and/or H63D genes may reduce iron intake by avoiding iron and mineral supplements, excess vitamin C, and uncooked seafood. If a patient is symptomatic, he/she may be advised to abstain from drinking alcohol.
With early detection and treatment, the prognosis is usually good. All potential symptoms are prevented if iron levels are kept within the normal range, which is possible if the diagnosis is made before an individual is symptomatic. If a patient is symptomatic but treated successfully before he/she develops liver cirrhosis, the patient's life expectancy is near normal. However, if left untreated, complications may arise which can be fatal. These include liver cancer, liver cirrhosis, diabetes mellitus, congestive heart failure, and difficulty depleting iron overload through phlebotomy. Liver biopsy can be helpful in determining prognosis of more severely affected individuals. Genetic testing may also be helpful, as variable severity has been noted in patients who have two C282Y genes compared to patients with two H63D genes or one of each. Men are two times more likely than women to develop severe complications. The prognosis for patients with idiopathic pulmonary hemosiderosis is fair, depending on detection and complications.
Screening for hemochromatosis is cost effective, particularly for certain groups of people. Relatives of patients with hemochromatosis—including children, siblings, and parents—should be tested by the most appropriate method. The best screening method may be iron and ferritin studies or genetic testing. If the affected person's diagnosis has been confirmed by genetic testing, relatives may have genetic testing to determine whether or not they have the genetic changes present in the affected individual. Many medical groups oppose genetic testing of children. Relatives who are affected but do not have symptoms can reduce iron intake and/or begin phlebotomy prior to the onset of symptoms, possibly preventing ever becoming symptomatic.
Population screening for hereditary hemochromatosis is being widely debated. Many doctors and scientists want population screening because hemochromatosis is easily and cheaply treated, and quite common. Arguments against treatment include the range of symptoms seen (and not seen) with certain gene mutations, and the risk of discrimination in health and life insurance. Whether or not population screening becomes favored by a majority, the publicity is beneficial. Hemochromatosis is a common, easily and effectively treated condition. However, diagnosis may be difficult because the presenting symptoms are the same as those seen with many other medical problems. The screening debate has the positive effect of increasing awareness and suspicion of hemochromatosis. Increased knowledge leads to earlier diagnosis and treatment of symptomatic individuals, and increased testing of their asymptomatic at–risk relatives.
Barton, James C., and Corwin Q. Edwards, eds. Hemochromatosis: Genetics, Pathophysiology, Diagnosis and Treatment. Cambridge: Cambridge University Press, 2000.
Crawford, Roberta. The Iron Elephant. Glyndon, MD: Vida Publishing, 1995.
"Iron Overload, Public Health and Genetics." Annals of Internal Medicine Supplement 129 (December 1998). <http://www.acponline.org/journals/annals/01dec98/supptoc.htm>.
Motulsky, A.G., and E. Beutler. "Population Screening for Hemochromatosis." Annual Review of Public Health 21 (2000): 65-79.
Wolfe, Yun Lee. "Case of the Ceaseless Fatigue." Prevention Magazine (July 1997): 88.
American Hemochromatosis Society, Inc. 777 E. Atlantic Ave., PMB Z-363, Delray Beach, FL 33483-5352. (561) 266-9037 or (888) 655-IRON (4766). email@example.com. <http://www.americanhs.org>.
American Liver Foundation. 75 Maiden Lane, Suite 603, New York, NY 10038. (800) 465-4837 or (888) 443-7222. <http://www.liverfoundation.org>.
Hemochromatosis Foundation, Inc. PO Box 8569, Albany, NY 12208-0569. (518) 489-0972. firstname.lastname@example.org. <http://www.hemochromatosis.org>.
Iron Disorders Institute, Inc. PO Box 3021, Greenville, SC 29602. (864) 241-0111. email@example.com. <http://www.irondisorders.org>.
Iron Overload Diseases Association, Inc. 433 Westwind Dr., North Palm Beach, FL 33408. (561) 840-8512. firstname.lastname@example.org.
"Hemochromatosis." GeneClinics. <http://www.geneclinics.org/profiles/hemochromatosis/>.
Hemochromatosis Information Sheet. National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) <http://www.niddk.nih.gov/health/digest/pubs/hemochrom/hemochromatosis.htm>.
Hereditary Hemochromatosis. Lecture by Richard Fass, MD, hematologist, Advanced Oncology Associates, given April 25, 1999. <http://www.advancedoncology.org/listen.htm> in Real Audio.
Michelle Q. Bosworth, MS, CGC