Introduction hemochromatosis was first identified in the 1800s, and by 1935 it was understood to be an inherited disease resulting in iron overload and deposition. The majority of patients with hereditary hemochromatosis display mutations in the gene coding for hfe, a protein that normally acts as an inhibitor of transepithelial iron transport. An independent licensee of the blue cross and blue shield association. Secondary hemochromatosis is caused by anemia, alcoholism, and other disorders. Hereditary hemochromatosis is an autosomal recessive disorder that disrupts the bodys regulation of iron. Hereditary hemochromatosis types 1, 2, and 3 darrell h. Haemochromatosis your questions answered booklet pdf. The hfe gene was identified as being responsible for. Hereditary hemochromatosis hh, most commonly due to mutations in the hh gene hfe, is a disorder in which increased intestinal iron absorption can lead to totalbody iron overload. People who inherit two abnormal genes will most likely develop hemochromatosis even with a normal diet, whereas those with a single gene. Classic hereditary hemochromatosis is caused by changes mutations of the hfe gene. Although its geographic distribution is worldwide, it is seen most commonly in populations of northern european origin, particularly nordic or celtic ancestry, in which it occurs with a prevalence of approximately 1 per 220250 individuals.
Hereditary haemochromatosis is characterised by excessive parenchymal iron deposition, particularly in the liver. Hereditary hemochromatosis is classified by type based on age of onset, genetic cause, and mode of inheritance. However, children or other family members who have pathogenic variants causing hemochromatosis may show symptoms of the disease. This blog post is based on a recent paper by grosse, gurrin, bertalli, and allen in genetics in medicine hereditary hemochromatosis hh attributable to mutations in the hfe gene is the most common autosomal recessive disorder among adults of northern european origin. Accumulation of excess iron results in damage to multiple organs including the liver, pancreas, heart, joints, and the brain. The evidence for genetic testing for hereditary hemochromatosis hfe gene in individuals who have abnormal iron indices, clinical signs of iron overload, or are first degree relatives of persons with hereditary hemochromatosis includes retrospective and prospective observational studies. Iron accumulation in classic hereditary hemochromatosis occurs slowly over many years. Genetic predisposition leads to disease in some but not all cases. However, not all individuals with hfe mutations develop iron overload. The diagnosis was confirmed by liver biopsy, which documented increased iron staining and elevated hepatic iron and iron index. Every person is unique, which must be taken into consideration before using some of these suggested diet modifications. Hemochromatosis from an underdiagnosed curiosity to a common disease.
Diagnosis is by elevated serum ferritin, iron, and transferrin saturation levels and. Description of procedure or service hereditary hemochromatosis hh, a common genetic disorder of iron metabolism, can lead to. The genetic condition of haemochromatosis is also detected by a blood test. Iron is an important nutrient that our bodies get from food. Hereditary hemochromatosis hh attributable to mutations in the hfe gene is the most common autosomal recessive disorder among adults of northern european origin. The disease results in a disruption in iron absorption due to genetic changes, and too much iron is absorbed from food. Without treatment, hemochromatosis can cause iron overload, a buildup of iron that can damage many parts of the body, including your liver, heart, pancreas, endocrine glands, and joints. The most important causes are hereditary haemochromatosis hhc, a genetic disorder, and transfusional iron overload, which can result from repeated blood transfusions. Usually hereditary haemochromatosis is not associated with neurological symptoms and iron deposition in the brain has not previously been described as a pathological phenomenon. This means that people with these types of hemochromatosis have a genetic change mutation or pathogenic variant in both copies of a gene. In most cases, an affected person has one parent with the condition. The increased iron enters the plasma and may be deposited in various target organs and may lead. We evaluated a 50yearold man for possible genetic hemochromatosis. The most common genetic mutation causing hh, an autosomal recessive disorder, is a mutation in the hfe for hereditary fe iron gene with homozygosity for the c282y mutation on chromosome 6.
Hemochromatosis genetic and rare diseases information. How i treat hemochromatosis blood american society of. The treatment for hemochromatosis is a simple process called phlebotomy, in which blood is drawn from the veins in the arm. Hereditary hemochromatosis is a genetic disorder that can cause severe liver disease and other health problems. Pdf hereditary hemochromatosis a new look at an old disease. Hereditary hemochromatosis rady childrens hospital. Manifestations can include systemic symptoms, liver disorders, cardiomyopathy, diabetes, erectile dysfunction, and arthropathy. If you have a family health history of hemochromatosis, talk to your doctor about testing for hereditary hemochromatosis. Hemochromatosis is an inherited disorder that causes the body to absorb extra iron. If you have hemochromatosis, your body absorbs more iron than it uses. Perhaps a more important question is whether the better predictor is the genotype or ferritin saturation measured by quantitating atoms of iron per molecule of ferritin 2, 3. Review diagnosis and treatment of hereditary hemochromatosis. Juvenile hemochromatosis is an earlyonset form of iron storage disease characterized by hypogonadotrophic hypogonadism and cardiomyopathy.
Hereditary hemochromatosis is a type of hemochromatosis caused by a change sometimes referred to as a mutation in one of the genes that controls iron absorption from food in the digestive tract. Hereditary hemochromatosis is an autosomal recessive inherited disorder that occurs in approximately 1 in 300 people, ultimately making them more susceptible to cirrhosis and liver failure. While many organs can be affected, iron overload is especially likely to affect the liver, heart, and pancreas. Hereditary hemochromatosis is a genetic disorder characterized by excessive iron fe accumulation that results in tissue damage. Table 1 demonstrates the differential diagnosis of iron overload in. Hereditary hemochromatosis heemuhkromuhtoesus is a genetic disease that causes the body to absorb and store too much iron. Hfeassociated hereditary hemochromatosis hfe hhc is characterized by inappropriately high absorption of iron by the gastrointestinal mucosa, resulting in excessive storage of iron particularly in the liver, skin, pancreas, heart, joints and testes. Beutler and associates 1 again raise the question of whether the better predictor of phenotypic expression of hemochromatosis is the genotype or transferrin saturation. This article discusses the presentation, testing, treatment and management of hereditary haemochromatosis. Introduction celtic curse also known as bronze diabetes hemochromatosis is the abnormal accumulation of iron in parenchymal organs, such as the liver, pancreas, and heart leading to. Hereditary haemochromatosis is a common inherited disorder in which excessive iron is absorbed and which, over time, may cause organ damage. Not all individuals with the homozygous recessive genotype have the disease, however. Hereditary hemochromatosis hh is an autosomal recessive disorder of iron metabolism.
Populations of northern european origin show the highest frequency of hh, with 1 in 300 individuals affected. Hereditary haemochromatosis is caused by mutations in the hfe gene. Hemochromatosis is inherited in an autosomal recessive manner. There are four types of hereditary hemochromatosis.
Humans, like most animals, have no means to excrete excess iron. Feb 15, 2018 hemochromatosis type 3 is a disease that shows reduced penetrance. Racgp hereditary haemochromatosis diagnosis and management. Persons who are homozygous for the hfe gene mutation c282y comprise 85. One in nine people carry the gene making hemochromatosis the most common genetic disorder in the united states. Iron overload or hemochromatosis indicates accumulation of iron in the body from any cause. A blood test also can tell if you have the hfe gene that causes the disease. Two blood tests can also be used to screen people who may have iron buildup due to hereditary hemochromatosis. Contribution of the h63d mutation in hfe to murine hereditary hemochromatosis. Hereditary hemochromatosis annals of internal medicine. Genes in the hjuv region that have been sequenced in either subject ii5 or iii3 in kindred a and found to have no mutations in coding regions pdf file, 228 kb. Excess iron accumulates in tissues and organs, disrupting their normal function. Hereditary hemochromatosis hematology and oncology.
Dec 18, 2001 beutler and associates 1 again raise the question of whether the better predictor of phenotypic expression of hemochromatosis is the genotype or transferrin saturation. Hereditary haemochromatosis or hemochromatosis is a genetic disorder characterized by excessive intestinal absorption of dietary iron, resulting in a pathological increase in total body iron stores. It can lead to liver damage, arthritis, heart problems, and diabetes. Hereditary hemochromatosis is inherited in an autosomal recessive or autosomal dominant manner, depending on which type a person has. Hereditary hemochromatosis hh remains the most common, identified. Hereditary hemochromatosis genetics home reference nih. Its in every red blood cell and is the main component of hemoglobin, the substance in red blood cells that carries oxygen away from the lungs to the. Hereditary hemochromatosis is difficult to diagnose because the symptoms look like other diseases. Recently, the putative causative gene loc148738 encoding a protein designated hemojuvelin was cloned. With this type of inheritance, one copy of the altered gene in each cell is sufficient to cause the disorder. We also noted the presence of macrocytosis in our small group of patients with hemochromatosis.
Hemochromatosis is a disorder in which extra iron builds up in the body to harmful levels. Hemochromatosis refers to a group of inherited disorders characterized by excessive dietary iron absorption, which in some cases can lead to severe iron overload. Iron overload indicates accumulation of iron in the body from any cause. Feb 01, 20 hereditary hemochromatosis is an autosomal recessive disorder that disrupts the bodys regulation of iron. Hemochromatosisfrom an underdiagnosed curiosity to a common disease. Hemochromatosis is a common heritable disorder characterized by the progressive accumulation of iron attributable to increased absorption from dietary sources. Genetic testing for hereditary hemochromatosis file name. Hereditary hemochromatosis is a disease in which your body has too much iron. Over time, the excess iron accumulates in tissues throughout the body, leading to iron overload. These organs cannot function normally because of iron overload. Hereditary hemochromatosis hh is an inher ited autosomal recessive iron overload disorder resulting in the failure of the normal hepcidin response to body. Hemochromatosis is a disorder in which the body stores too much iron. Patients with excessive iron loading are at risk of developing cirrhosis, hepatocellular cancer, car. Your doctor will ask you about your symptoms, do a physical exam, and order blood tests to check the amount of iron in your blood and liver.
Hfe gene mutation, c282y causing hereditary hemochromatosis in caucasians is extremely rare in korean population. Type 4 hemochromatosis is distinguished by its autosomal dominant inheritance pattern. Dec 18, 2001 we also noted the presence of macrocytosis in our small group of patients with hemochromatosis. These two mutations are responsible for almost 90% of people with inherited causes of iron overload. The authors of several large populationbased studies have performed hemochromatosis genetic testing on participants many years into the study and used stored blood samples to measure sf over time in participants found to have c282y homozygosity.
Hereditary haemochromatosis diagnosis and management racgp. Individuals may develop cirrhosis of the liver, liver tumors, diabetes, arthritis, andor heart disease. Hereditary hemochromatosis choose your test system for the reliable diagnostics of hereditary hemochromatosis. Men have a 24fold increased rate of ironoverload disease compared with women. Preventive services task force recommends against routine genetic screening for hereditary hemochromatosis in the asymptomatic general population, but states that individuals with a family member, especially a sibling, who is known to have hereditary hemochromatosis should be counseled regarding genetic testing. This mutation is inherited in an autosomal recessive pattern. Hereditary hemochromatosis ahs m2012 notification file name.
Evaluation and diagnosis of hh requires integration of genetic. Diagnosis and management of hereditary hemochromatosis. Jul 27, 2012 summary hemochromatosis is completely treatable. Routine genetic testing can help diagnose hereditary hemochromatosis. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Hemochromatosis types 1, 2, and 3 are inherited in an autosomal recessive manner. Accumulation of iron in the organs is toxic and can cause organ damage. Early symptoms of hemochromatosis type 3 can include fatigue, weakness, and joint pain. Other mediators that affect iron absorption, transport. Hereditary hemochromatosis, a common condition caused by hfe gene mutations, can lead to excess iron storage and disease but clinical penetrance of hfe gen. Hereditary hemochromatosis hh omim 235200 is an autosomal recessive disorder of iron metabolism resulting in the accumulation of excess iron in a variety of organs.
Get a printable copy pdf file of the complete article 1. Haplotypes of the hjv l101p and c80r mutations in kindred a as defined by snps and microsatellite d1s3466 in the region surrounding the hjv gene pdf file, 104 kb pdf file table s3. Hereditary hemochromatosis merck manuals professional edition. In 1996, identification of the hemochromatosis gene, hfe, was reported. Rare forms of hereditary hemochromatosis include type 2 a and b, juvenile hemochromatosis caused by hjv and hamp mutation, type 3 related to tfr2 mutation, and type 4 a and b, ferroportin. The excess iron is stored in the bodys tissues and organs, particularly the skin, heart, liver, pancreas, and joints. Over time, the extra iron builds to toxic levels in vital organs such as the heart, pancreas, liver, joints, and pituitary. Hemochromatosis awarenessdiseasesresourcesgenomicscdc. Each biological child of a person with the autosomal dominant form of. Feb 15, 2018 hemochromatosis may be hereditary, meaning it is caused by genetic changes mutations or pathogenic variants to any of several genes including fth1, hamp, hfe, hfe2 also known as hjv, slc40a1, and tfr2. Genetic abnormalities and juvenile hemochromatosis. Ws blood work show a serum ferritin level of 1,048 ngml normal in men, 18 to 270 ngml and transferrin iron saturation ts of 95% normal in men, 10% to 50%.
Hereditary hemochromatosis hh is an autosomal recessive disorder that affects one in three hundred people in the united states. In the united states, the most common form of hemochromatosis in adults is hereditary hemochromatosis. The most common form of hemochromatosis is known by several different names including hemochromatosis type i, hferelated hemochromatosis, hereditary hemochromatosis and classic hereditary hemochromatosis. However, those who do not may suffer organ damage, etc. Individuals with the disease, if they seek help promptly, can live totally normal lives. The previously proposed designation of this gene as hfe2 is contrary to established convention, because it is not a member of. Hemochromatosis type 3 is a disease in which too much iron builds up in the body. Facts five out of a thousand people have an increased risk of developing hereditary hemochromatosis hh. It is primarily seen in middleaged men of northern european descent, and postmenopausal women. Hereditary hemochromatosis is a disorder that causes the body to absorb too much iron from the diet. Hereditary hemochromatosis is distinct from secondary iron overload, which also causes increased iron absorption and increased iron deposition. Today, hemochromatosis is defined as a metabolic disorder affecting iron absorption, and resulting in the accumulation of excess iron in the bodys organs. Hereditary hemochromatosis hh is an inher ited autosomal recessive iron overload disorder resulting in the failure of the normal hepcidin response to body iron stores, leading to increased duodenal absorption of dietary iron. It occurs in 1 in 300 nonhispanic whites in the united states.
The most common form among caucasian populations of northern european. General recommendations for management of hereditary hemochromatosis for iron depletion, weekly or biweekly whole blood phlebotomy for a total of 1012 phlebotomies with a serum ferritin goal of 50100 ugml once ferritin goal is achieved, maintenance phlebotomy schedules should be implemented. Aug 16, 2017 hereditary hemochromatosis hh attributable to mutations in the hfe gene is the most common autosomal recessive disorder among adults of northern european origin. Hereditary hemochromatosis hh is now recognized to comprise a number of inherited disorders that can lead to progressive iron loading. Hereditary hemochromatosis american family physician. Hereditary hemochromatosis hh is defined as an inherited iron overload disorder characterized by excessive absorption of iron, due to. Hereditary hemochromatosis hh remains the most common, identi. Diagnosis and treatment of hereditary hemochromatosis. Early diagnosis and treatment is critical to prevent complications from the disorder.
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