Materiały źródłowe

• #1 Hemochromatosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430862/

  Hemochromatosis is a disorder characterized by excessive iron accumulation in body tissues that leads to the dysfunction of various organs. […] Hereditary hemochromatosis, the most common form, is an autosomal recessive disorder predominantly found in individuals of European descent. The disorder is caused by mutations in HFE, resulting in increased iron absorption. […] Type 1 hereditary hemochromatosis occurs in patients who are typically homozygous for loss-of-function mutations in HFE. These mutations cause increased iron absorption despite an average dietary iron intake. […] Type 2 hereditary hemochromatosis is also inherited in an autosomal recessive fashion without a predilection for either sex. […] Type 3 hereditary hemochromatosis, also inherited in an autosomal recessive fashion, has a typical age of onset of 30 to 40 years. This type is due to mutations in the transferrin-receptor gene (TFR2) on chromosome 7.

• #1 Hereditary Haemochromatosis (Causes, Symptoms, and Treatment)

  https://patient.info/doctor/hereditary-haemochromatosis

  Hereditary haemochromatosis (HHC) is a heterogeneous group of disorders related to deficiency of the iron regulatory hormone hepcidin. HHC is an autosomal recessive genetic disease in which increased intestinal absorption of iron causes accumulation in tissues, especially the liver, which may lead to organ damage. […] Defects of the HFE gene (located on the short arm of chromosome 6) cause the majority of cases of inherited haemochromatosis, which is therefore often referred to as HFE haemochromatosis (HFE-HC). […] A systematic review has shown that about 0.4% of people of northern European descent have the genetic mutation that increases the risk of developing haemochromatosis but the clinical penetrance of the mutation is much lower than the genetic prevalence. […] The known mutations of the HFE gene are C282Y and H63D. The C282Y mutation is most common in white populations.

• #1 Hereditary Hemochromatosis – Hematology and Oncology – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hematology-and-oncology/iron-overload/hereditary-hemochromatosis

  Hereditary hemochromatosis is a genetic disorder characterized by excessive iron (Fe) accumulation that results in tissue damage. There are 4 types of hereditary hemochromatosis, types 1 through 4, depending on the gene that is mutated. Type 1: Mutations of the HFE (human homeostatic iron regulator) gene. Type 2A and type 2B (juvenile hemochromatosis): Mutations in the HJV (type 2A, hemojuvelin BMP co-receptor) and HAMP (type 2B, hepcidin antimicrobial peptide) genes. Type 3: Mutations in the TFR2 (transferrin receptor 2) gene. Type 4A and type 4B (ferroportin disease): Mutations in the SLC40A1 (solute carrier family 40 member 1) gene in both types 4A (diminished export function of ferroportin) and 4B (resistance of ferroportin to hepcidin). Other much rarer genetic disorders can cause hepatic iron overload, but the clinical picture is usually dominated by symptoms and signs due to failure of other organs. Although these types vary markedly in age of onset, clinical consequences of iron overload are the same in all types. Type 1a is classic hereditary hemochromatosis, also termed HFE-related hemochromatosis, and more than 80% of cases are caused by the homozygous C282Y mutation. Type 1b hemochromatosis is caused by C282Y/H63D compound heterozygote mutations and results in clinically significant iron overload in only 0.5 to 2% of affected individuals. The disorder is autosomal recessive, with a homozygous frequency of 1:200 and a heterozygous frequency of 1:8 in people of Northern European ancestry. The C282Y and H63D mutations are uncommon among people with African ancestry and rare among people with Asian ancestry. Of patients with clinical features of hemochromatosis, 83% are homozygous. However, for unknown reasons, phenotypic (clinical) disease is much less common than predicted by the frequency of the gene. Type 2 hereditary hemochromatosis is a rare autosomal recessive disorder caused by mutations in the HJV gene that affect the transcription protein hemojuvelin (type 2A), or mutations in the HAMP gene, which directly codes for hepcidin, a peptide hormone made in the liver and involved in iron homeostasis (type 2B). Type 3 hereditary hemochromatosis occurs due to mutations in transferrin receptor 2 (TFR2) gene that codes for a protein that appears to control saturation of transferrin. Type 4 hereditary hemochromatosis occurs largely in people of southern European ancestry. It results from an autosomal dominant mutation in the SLC40A1 gene and affects the ability of ferroportin, an iron-transport protein, to bind hepcidin. In type 4A disease, hepcidin production is normal but the export function of ferroportin is reduced, leading to intracellular iron retention and low plasma iron levels, normal or low transferrin saturation, and elevated serum ferritin levels. In type 4B disease, there is resistance of ferroportin to hepcidin leading to iron overload because ferroportin does not respond to hepcidin’s regulatory effects, causing excessive iron export from cells into the plasma. The clinical consequences of iron overload tend to be similar regardless of the etiology and pathophysiology of the overload.

• #1 Hereditary hemochromatosis: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/hereditary-hemochromatosis/

  Hereditary hemochromatosis is a disorder that causes the body to absorb too much iron from the diet. […] Mutations in several genes can cause hereditary hemochromatosis. Type 1 hemochromatosis results from mutations in the HFE gene, and type 2 hemochromatosis results from mutations in either the HJV or HAMP gene. Mutations in the TFR2 gene cause type 3 hemochromatosis, and mutations in the SLC40A1 gene cause type 4 hemochromatosis. […] The proteins produced from these genes play important roles in regulating the absorption, transport, and storage of iron in the body. Mutations in any of these genes impair the control of the intestine’s absorption of iron from foods during digestion and alter the distribution of iron to other parts of the body. As a result, iron accumulates in tissues and organs, which can disrupt their normal functions.

• #1 Hemochromatosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430862/

  Type 4 hereditary hemochromatosis is the only known type to be inherited in an autosomal dominant fashion. […] Causes of secondary hemochromatosis include erythropoietic hemochromatosis, a condition that results from excess iron absorption because the patient is producing excessive amounts of red blood cells. […] Excessive iron consumption can also cause hemochromatosis. Historically, this has resulted from drinking beer prepared in steel drums. Accidental and intentional overdoses of iron can result from the consumption of some over-the-counter dietary supplements.

• #1 Hemochromatosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/177216-overview

  Hereditary hemochromatosis is a genetic heterogeneous disorder inherited as an autosomal recessive trait. The gene is tightly linked to the human leukocyte antigen (HLA)-A region on the short arm of chromosome 6. HFE, a specific gene for hemochromatosis, has been identified. […] Homozygosity for a missense mutation, with substitution of a cysteine residue for a tyrosine residue at amino acid position 282 (C282Y) of HFE is found in 70-100% of clinically diagnosed patients. A second missense mutation, with substitution of histidine for aspartate at amino acid 63 (H63D), has also been identified. The clinical effects of this mutation appear to be limited. […] C282Y homozygotes and, possibly, C282Y/H63D compound heterozygotes, appear to be at risk for clinical iron overload. The precise mechanism by which mutations in the HFE gene lead to iron overload is unknown. The outcome is increased intestinal iron absorption and predominantly hepatocellular accumulation of hepatic iron. […] Evidence indicates that certain forms of hereditary hemochromatosis are caused by hepcidin deficiency. Studies suggest that TfR2 is a modulator of hepcidin production in response to iron; hepcidin was low or undetectable in most cases of patients homozygous for TfR2 mutation.

• #1 Hereditary haemochromatosis – Wikipedia

  https://en.wikipedia.org/wiki/Hereditary_haemochromatosis

  Homozygosity for the C282Y genetic variant is the most common genotype responsible for clinical iron accumulation, though heterozygosity for C282Y/H63D variants, so-called compound heterozygotes, results in clinically evident iron overload. […] Individuals with the relevant genetic variants may never develop iron overload.

• #1 Patient education: Hereditary hemochromatosis (Beyond the Basics) – UpToDate

  https://www.uptodate.com/contents/hereditary-hemochromatosis-beyond-the-basics

  In fact, most people do not develop iron overload even if the HFE C282Y variant is inherited from both parents. […] The reasons some people develop iron overload and some do not are still being studied. […] Hemochromatosis refers to a genetic disorder characterized by excess iron in the body. […] Hemochromatosis typically occur in individuals who inherit two copies of the C282Y variant in the HFE gene (one from the mother and one from the father). Many people who inherit two copies of the HFE C282Y variant will not develop hemochromatosis.

• #1

  https://www.nhs.uk/conditions/haemochromatosis/

  Haemochromatosis is caused by a faulty gene that affects how the body absorbs iron from your diet. […] You’re at risk of developing the condition if both of your parents have this faulty gene and you inherit 1 copy from each of them. […] You will not get haemochromatosis if you only inherit 1 copy of the faulty gene but there’s a chance you could pass the faulty gene on to any children you have. […] If you do inherit 2 copies, you will not necessarily get haemochromatosis. Only a small number of people with 2 copies of this faulty gene will ever develop the condition. It’s not known exactly why this is.

• #1 Hemochromatosis – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/hemochromatosis/symptoms-causes/syc-20351443

  Hemochromatosis is most often caused by a change in a gene. This gene controls the amount of iron the body absorbs from food. The altered gene is passed from parents to children. This type of hemochromatosis is by far the most common type. It’s called hereditary hemochromatosis. […] A gene called HFE is most often the cause of hereditary hemochromatosis. You inherit one HFE gene from each of your parents. The HFE gene has two common mutations, C282Y and H63D. Genetic testing can reveal whether you have these changes in your HFE gene. […] If you inherit two altered genes, you may develop hemochromatosis. You also can pass the altered gene on to your children. But not everyone who inherits two genes develops problems linked to the iron overload of hemochromatosis. […] If you inherit one altered gene, you’re unlikely to develop hemochromatosis. However, you are considered a carrier and can pass the altered gene on to your children. But your children wouldn’t develop the disease unless they also inherited another altered gene from the other parent. […] Many people have gene changes that cause hemochromatosis. However, not everyone develops iron overload to a degree that causes tissue and organ damage.

• #1

  https://www.everlywell.com/blog/news-and-info/what-causes-hemochromatosis/?srsltid=AfmBOorlvimAAv3w-Xns3xOn0HdFB91r1K-SKrDaB4U5Gs9eNX_TYubT

  Hereditary hemochromatosis is caused by an HFE mutation in the gene that controls the amount of iron that you absorb from food. Normally, the liver tissue secretes a hormone called hepcidin that regulates iron usage and absorption and determines how excess iron is stored. With hereditary hemochromatosis, the HFE gene mutation disrupts the function of hepcidin, preventing it from properly regulating iron usage. The result is excess absorption of iron from food. […] Some people without the hereditary form of hemochromatosis may develop whats known as secondary hemochromatosis. Secondary hemochromatosis comes as a side effect of certain medical treatments or medical conditions that contribute to an iron overload, including: Blood transfusion, Treatment for anemia, Iron supplements or injections, Extended use of kidney dialysis, Treatment for liver disease.

• #1 Hemochromatosis (Iron Overload): Causes, Symptoms, Treatment, Diet & More

  https://my.clevelandclinic.org/health/diseases/14971-hemochromatosis-iron-overload

  Hemochromatosis, or iron overload, is a condition in which your body stores too much iron. Its often genetic. […] An inherited genetic change is the most common cause. Its called primary hemochromatosis, hereditary hemochromatosis or classical hemochromatosis. With primary hemochromatosis, problems with the DNA come from both parents and cause the body to absorb too much iron. […] In secondary hemochromatosis, medical treatments or other medical conditions cause the iron overload. Examples include: Anemia (low amount of red blood cells), Blood transfusions, Iron pills or injections, Kidney dialysis over a long period of time, Liver disease, such as hepatitis C infection or fatty liver disease. […] The inherited form of hemochromatosis is more common in white people with ancestors from Northern Europe. […] Other factors that increase the chances of developing hemochromatosis include alcohol abuse and a family history of: Arthritis, Diabetes, Heart attack, Erectile dysfunction, Liver disease.

• #1 Hemochromatosis – Types, Symptoms, Causes, Diagnosis, Treatment

  https://www.webmd.com/a-to-z-guides/what-is-hemochromatosis

  Hemochromatosis is a disorder where too much iron builds up in your body. Sometimes, its called iron overload. […] The HFE gene controls how much iron your body stores from the food you eat. Two hemochromatosis mutations, C282Y and H63D, are thought to be responsible for most of the hereditary cases of the condition. […] Other genes are also responsible for a small number of cases, about 10%-15%. These are called non-HFE hemochromatosis genes. If you have mutations of the HJV or HAMP genes, you usually have symptoms when you are young and may have cirrhosis (scarring of the liver) by the time you are a teenager. […] This type usually happens when someone gets a lot of blood transfusions because of conditions such as severe anemia (sickle cell anemia) or bone marrow failure. The red blood cells given during a transfusion have a lot of iron. The body doesn’t have a good way to remove iron from your system, so it can lead to a buildup of the mineral. […] Buildup can also happen in the liver when it is damaged through cirrhosis or advanced, chronic hepatitis B or C.

• #1 Secondary Hemochromatosis: Symptoms, Causes, Treatment, and Outlook

  https://www.healthline.com/health/secondary-hemochromatosis

  Secondary hemochromatosis is when iron builds up in your tissue due to an underlying medical condition and not due to your genetics. […] Its most commonly caused by chronic blood transfusions used to treat conditions that cause low red blood cell counts. […] The most common cause of secondary hemochromatosis is chronic blood transfusions. […] Other potential causes of secondary hemochromatosis are: increased iron absorption by your intestines due to the ineffective production of red blood cells, iron poisoning from iron supplements or other sources of iron, underlying conditions such as cirrhosis, steatohepatitis, porphyria cutanea tarda, advanced hepatitis B or hepatitis C. […] Very rarely, excess dietary iron intake can lead to secondary hemochromatosis. […] Secondary hemochromatosis is more common in children than primary hemochromatosis.

• #1 What Causes Hemochromatosis? | Hematology-Oncology Associates of CNY

  https://www.hoacny.com/patient-resources/blood-disorders/what-hemochromatosis/what-causes-hemochromatosis

  Primary hemochromatosis is caused by a defect in the genes that control how much iron you absorb from food. […] The genes usually involved in primary hemochromatosis are called HFE genes. Faulty HFE genes cause the body to absorb too much iron. […] Although less common, other faulty genes also can cause hemochromatosis. Researchers continue to study what changes to normal genes may cause the disease. […] Secondary hemochromatosis usually is the result of another disease or condition that causes iron overload. […] Other factors also can cause secondary hemochromatosis, including: Blood transfusions, Oral iron pills or iron injections, with or without very high vitamin C intake (vitamin C helps your body absorb iron), Long-term kidney dialysis.

• #1 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Hemochromatosis-Causes.aspx

  Hemochromatosis is an iron overload disorder. The affected individual stockpiles iron in the body to the extent that it accumulates to an undesirable amount at various locations, causing harm to the normal functioning of the tissue in which it is stored. […] The main causes which result in hemochromatosis are as mentioned below: A defective genetic make-up, which results in increased iron absorption via the gastrointestinal tract and the excess iron accumulates in the organs such as the heart. This type of hemochromatosis usually remains undiagnosed until the symptoms appear. An excess iron accumulation post blood transfusions in blood-related disorders such as anemia and thalassemia. Prolonged alcohol consumption may also contribute to hemochromatosis. […] Primary or hereditary hemochromatosis exists in several forms, of which Type 1 is the most common.

• #1 Symptoms & Causes of Hemochromatosis – NIDDK

  https://www.niddk.nih.gov/health-information/liver-disease/hemochromatosis/symptoms-causes

  Mutations in genes that control how the body absorbs iron cause primary hemochromatosis. The most common mutations are in the HFE genes and are called C282Y and H63D. […] The important HFE mutations are autosomal recessive, meaning that a person must inherit two copies of the HFE gene with the mutation to have hemochromatosis. […] Mutations in other genes that control how the body manages iron levels cause 10 to 15 percent of cases of primary hemochromatosis. […] Secondary hemochromatosis is caused by excessive iron in the diet or from multiple blood transfusions. […] The usual cause of secondary hemochromatosis is blood transfusions given for severe types of anemia, such as sickle cell disease or thalassemias. […] Iron overload from excess iron in the diet is very rare but can be caused by cooking and brewing alcohol in crude iron pots or skillets. […] Neonatal hemochromatosis occurs when a pregnant woman’s immune system produces antibodies that damage the liver of a fetus, causing iron overload.

• #1 Haemochromatosis

  https://www.chemeurope.com/en/encyclopedia/Haemochromatosis.html

  Haemochromatosis, also spelled hemochromatosis, is a hereditary disease characterized by improper dietary iron metabolism (making it an iron overload disorder), which causes the accumulation of iron in a number of body tissues. […] „Hemochromatosis” also refers to the concept of hereditary hemochromatosis, in which certain genetic mutations can predispose people to iron accumulation. However, the two are not always related; not all cases of iron overload are associated with genetic causes, and having such hereditary markers does not necessarily cause significant iron overload. […] There exist other causes of excess iron accumulation, which have to be considered before Haemochromatosis is diagnosed. […] African iron overload, formerly known as Bantu siderosis, was first observed among people of African descent in Southern Africa.

• #1 Hemochromatosis | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/haemochromatosis?lang=us

  This makes hemochromatosis one of the most common genetic disorders in Caucasians of Northern European ancestry. […] Secondary hemochromatosis is rare and is usually seen in association with diseases that chiefly cause hemosiderosis. […] Etiology: frequent transfusion mainly depositional siderosis in the reticuloendothelial system (RES) if 40 units transfused: then may cause hemochromatosis (non-RES iron deposition). […] high erythrogenic requirements (hemolytic anemia, myelodysplasia) mainly depositional siderosis in RES from transfusion increased duodenal iron absorption may lead to hemochromatosis (non-RES iron deposition). […] Bantu siderosis: rare cause in Africa due to iron-laden locally-brewed beer.

• #1 Patient education: Hereditary hemochromatosis (Beyond the Basics) – UpToDate

  https://www.uptodate.com/contents/hereditary-hemochromatosis-beyond-the-basics/print

  In fact, most people do not develop iron overload even if the HFE C282Y variant is inherited from both parents. The reasons some people develop iron overload and some do not are still being studied. […] […] Risk factors — In the United States, approximately 5 in every 1000 people of European ancestry (0.5 percent) have hereditary hemochromatosis, although some are unaware of it. Relatives of people with the HFE C282Y variant should undergo testing since they may have the variant without knowing it. […] […] Iron overload is more likely to be seen in males than in females and at a younger age in males than females.

• #1 Iron overload – Wikipedia

  https://en.wikipedia.org/wiki/Iron_overload

  The causes of hemochromatosis broken down into two subcategories: primary cases (hereditary or genetically determined) and less frequent secondary cases (acquired during life). People of Northern European descent, including Celtic (Irish, Scottish, Welsh, Cornish, Breton etc.), English, and Scandinavian origin have a particularly high incidence, with about 10% being carriers of the principal genetic variant, the C282Y mutation on the HFE gene, and 1% having the condition. […] The overwhelming majority depend on mutations of the HFE gene discovered in 1996, but since then others have been discovered and sometimes are grouped together as „non-classical hereditary hemochromatosis”, „non-HFE related hereditary hemochromatosis”, or „non-HFE hemochromatosis”. […] The causes of hemochromatosis broken down into two subcategories: primary cases (hereditary or genetically determined) and less frequent secondary cases (acquired during life).

• #1 Hemochromatosis (Iron Overload) – Causes, Symptoms and Treatment | Apollo Hospitals

  https://www.apollohospitals.com/diseases-and-conditions/hemochromatosis-iron-overload-causes-symptoms-and-treatment/

  Descent: Hereditary hemochromatosis is more common in Northern Europeans as compared to any other ethnicity. […] Frequent blood transfusions can increase the amount of iron in your body and give rise to secondary hemochromatosis. […] If hemochromatosis is left untreated, the excess iron gets deposited in various organs and can cause organ damage. […] In the liver, excess iron can cause liver cirrhosis (permanent scarring of the liver). It increases the risk of developing liver cancer. […] Iron deposition in the pancreas can damage the cells responsible for producing insulin, causing an increased risk for type 1 diabetes. […] Iron deposition in the heart can cause cardiomyopathy. It can also cause abnormal heartbeats (arrhythmia) and congestive heart failure. […] There is no cure for hemochromatosis. However, treatments can reduce iron levels in the blood.

• #1 Hereditary Hemochromatosis | Cedars-Sinai

  https://www.cedars-sinai.org/health-library/diseases-and-conditions/h/hereditary-hemochromatosis.html

  Hereditary hemochromatosis is a genetic disease. This means it is passed down from parents through their genes. It is most common in white people whose families are from Northern Europe. […] You may be born with this condition if you inherit two hemochromatosis genes, one from each parent. […] If parents without hemochromatosis have a child with the disorder, there is a 25% chance that any additional child may be born with the disease. […] It’s more common for men with this condition to have too much iron. Men also tend to show symptoms at a younger age than women. This is likely because women lose iron each month when they have their menstrual period.

• #1 Haemochromatosis – Haemochromatosis Australia

  https://haemochromatosis.org.au/haemochromatosis/

  Hereditary haemochromatosis (inherited iron overload disorder) is the most common genetic disorder in Australia. About 1 in 200 people of northern European origin have the genetic risk for haemochromatosis. […] Haemochromatosis can affect the body’s ability to regulate iron absorption and can lead to too much iron being taken up and stored. It is this excess iron which can cause harm. […] There are two main mutations or faults that cause hereditary haemochromatosis. These are referred to as C282Y and H63D. The C282Y mutation is associated with most cases of hereditary haemochromatosis. […] Haemochromatosis is a recessive gene disorder. That means for the condition to be passed on, both mother and father must have one copy of the abnormal HFE gene. […] 1 in 700 people with haemochromatosis have no mutation in the HFE gene. This is known as Non-HFE haemochromatosis and is due to mutations in other genes.

• #1 Haemochromatosis | Better Health Channel

  https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/haemochromatosis

  Haemochromatosis is a common inherited disorder, which causes the body to absorb more iron than usual from food. […] Haemochromatosis is a recessive gene disorder caused by mutations of the haemochromatosis (HFE) gene. To develop a recessive gene disorder a person needs to inherit the gene mutation from both parents. If a person inherits only one mutated HFE gene, they are known as carriers. […] Around one in seven people carry the mutated HFE gene. A carrier wont develop the condition themselves, but may pass the mutation on to their children. If two carriers conceive, their child has a 50 per cent chance of inheriting one mutated HFE gene and becoming a carrier, and a one in four chance of inheriting both mutated HFE genes and developing the disease.

• #1 Hereditary Haemochromatosis (Causes, Symptoms, and Treatment)

  https://patient.info/doctor/hereditary-haemochromatosis

  HHC is a relatively common genetic disorder in northern European populations and is probably under-diagnosed. […] Haemochromatosis is inherited in an autosomal recessive pattern but the clinical picture is more complex because the expression (penetrance) of the gene varies. This means that not everyone who is homozygous for HHC genes will develop clinical disease. The variation in gene expression may be due to other factors affecting iron accumulation. […] There are rarer forms of inherited haemochromatosis, where patients have 'classical’ clinical features of haemochromatosis but lack mutations in the HFE gene. […] Juvenile haemochromatosis is an inherited condition in which there is clinical onset in the second or third decade. The gene responsible is probably located on chromosome 1.

• #1 Haemochromatosis – symptoms and treatment | healthdirect

  https://www.healthdirect.gov.au/haemochromatosis

  Haemochromatosis causes your body to take in and store too much iron. […] Haemochromatosis is an inherited condition. […] Haemochromatosis is caused by a faulty gene that affects how your body absorbs iron from food. […] Haemochromatosis most often affects people of white, northern European background. […] You’re at risk of getting haemochromatosis if both of your parents have the faulty gene AND you inherit a copy from each of them. […] However, you will not necessarily get haemochromatosis. Only some people with 2 copies of this faulty gene develop the condition. It’s not known exactly why this is. […] Haemochromatosis is a genetic condition, meaning you are born with the genes that cause it. But only some people with faulty genes develop the condition, and early treatment can help prevent serious problems from haemochromatosis.

• #1 Hereditary Hemochromatosis

  https://ketteringhealth.org/conditions/hereditary-hemochromatosis/

  Hereditary hemochromatosis is a genetic disease. This means it is passed down from parents through their genes. It is most common in white people whose families are from Northern Europe. Men and women are equally affected by the disease. Hereditary hemochromatosis is one of the most common genetic disorders in the U.S. […] You may be born with this condition if you inherit two hemochromatosis genes, one from each parent. If you have only one of these genes, you are called a carrier of the gene. You don’t have symptoms. But you have a greater chance of having a child with this disease. […] If parents without hemochromatosis have a child with the disorder, there is a 25% chance that any additional child may be born with the disease. Parents, children, and siblings (first-degree relatives) of people with hemochromatosis should be screened for the disorder.

• #1 Hemochromatosis // Middlesex Health

  https://middlesexhealth.org/learning-center/diseases-and-conditions/hemochromatosis

  Many people have gene changes that cause hemochromatosis. However, not everyone develops iron overload to a degree that causes tissue and organ damage. […] Hereditary hemochromatosis isn’t the only type of hemochromatosis. Other types include: Juvenile hemochromatosis. This causes the same problems in young people that hereditary hemochromatosis causes in adults. But iron buildup begins much earlier, and symptoms usually appear between the ages of 15 and 30. This condition is caused by changes in the hemojuvelin or hepcidin genes. […] Neonatal hemochromatosis. In this serious disease, iron builds up quickly in the liver of the developing baby in the womb. It is thought to be an autoimmune disease, in which the body attacks itself. […] Secondary hemochromatosis. This form of the disease is not inherited and is often referred to as iron overload. People with certain types of anemia or liver disease may often need multiple blood transfusions. This can lead to excess iron buildup.

• #1 Hemochromatosis (Iron Overload): Types, Causes, and Symptoms

  https://www.verywellhealth.com/hemochromatosis-8603438

  Juvenile hemochromatosis starts to have effects before age 30. It can cause delayed puberty, heart disease, diabetes, joint pain, and liver disease. This condition is caused by the inheritance of abnormal variations of HAMP or HJV genes, and it is inherited in an autosomal recessive pattern. […] Neonatal hemochromatosis is a rare disorder that affects newborns. It is caused by damage to the infant’s liver that might result from the birthing parent’s immune system. The liver damage causes excess iron accumulation in the baby’s body. […] Secondary hemochromatosis is iron buildup due to medical risks, which include repeated blood transfusions or liver disease.

• #1 Causes Of Hemochromatosis: Understanding The Genetic Factors

  https://drniveditapandey.com/hemochromatosis/causes-of-hemochromatosis-understanding-the-genetic-factors/

  Hereditary hemochromatosis is a disorder that makes the body take in too much iron from the diet. […] The main causes of hemochromatosis are because of genetics. Certain gene changes lead to this condition. […] Hemochromatosis happens when the body cant manage iron well. A hormone called hepcidin, made in the liver, usually helps with this. It decides how much iron from food is used and stored by our body. […] Changes in the HFE gene often lead to the most seen type of hemochromatosis. These changes, specifically C282Y and H63D, make the body absorb too much iron. […] Though the HFE gene is key in type 1 hemochromatosis, other gene changes can lead to different types. Genes like HAMP, TFR2, and SLC40A1 also play a big part in iron control. […] Hemochromatosis types can be passed down differently. Types 1, 2, and 3 are passed in a certain way that needs both parents to give a changed gene. But, type 4 only needs one changed gene from either parent.

• #1 Genetic condition haemochromatosis linked to higher levels of disease in older people – News

  https://news.exeter.ac.uk/faculty-of-health-and-life-sciences/genetic-condition-haemochromatosis-linked-to-higher-levels-of-disease-in-older-people/

  These findings highlight the need for earlier diagnosis of iron overload, as many people with the high risk genetic variants are currently diagnosed too late to prevent organ damage. […] This important data supports the long-held belief that we should be using targeted genetic testing more consistently to make an earlier and more accurate diagnosis of haemochromatosis.

• #1 Genetic condition haemochromatosis linked to higher levels of disease in older people – News

  https://news.exeter.ac.uk/faculty-of-health-and-life-sciences/genetic-condition-haemochromatosis-linked-to-higher-levels-of-disease-in-older-people/

  A largescale new study has found that some people whose genetics are linked to the common iron overload condition haemochromatosis have substantially greater levels of liver, musculoskeletal and brain disease than previously reported, especially at older ages. […] Haemochromatosis causes a build-up of iron in the body which can cause harm to joints and organs although the extent of this harm is unclear, especially in older ages. […] Our study is the most comprehensive to date and reveals higher levels of death and organ and joint damage than previously known, including liver disease and joint replacements. […] Haemochromatosis is more common in males, and particularly affects white people of Northern European ancestry. […] An estimated 175,000 men of European ancestry in the UK have the two gene variations that cause haemochromatosis.

• #2 Iron overload – Wikipedia

  https://en.wikipedia.org/wiki/Iron_overload

  Iron overload (also known as haemochromatosis or hemochromatosis) is the abnormal and increased accumulation of total iron in the body, leading to organ damage. The primary mechanism of organ damage is oxidative stress, as elevated intracellular iron levels increase free radical formation via the Fenton reaction. Iron overload is often primary (i.e. hereditary haemochromatosis) but may also be secondary to repeated blood transfusions (i.e. transfusional iron overload). […] The term hemochromatosis was initially used to refer to what is now more specifically called hemochromatosis type 1 (or HFE-related hereditary hemochromatosis). Currently, hemochromatosis (without further specification) is mostly defined as iron overload with a hereditary or primary cause, or originating from a metabolic disorder. However, the term is currently also used more broadly to refer to any form of iron overload, thus requiring specification of the cause, for example, hereditary hemochromatosis.

• #2 Hereditary Haemochromatosis (Causes, Symptoms, and Treatment)

  https://patient.info/doctor/hereditary-haemochromatosis

  Hereditary haemochromatosis (HHC) is a heterogeneous group of disorders related to deficiency of the iron regulatory hormone hepcidin. HHC is an autosomal recessive genetic disease in which increased intestinal absorption of iron causes accumulation in tissues, especially the liver, which may lead to organ damage. […] Defects of the HFE gene (located on the short arm of chromosome 6) cause the majority of cases of inherited haemochromatosis, which is therefore often referred to as HFE haemochromatosis (HFE-HC). […] A systematic review has shown that about 0.4% of people of northern European descent have the genetic mutation that increases the risk of developing haemochromatosis but the clinical penetrance of the mutation is much lower than the genetic prevalence. […] The known mutations of the HFE gene are C282Y and H63D. The C282Y mutation is most common in white populations.

• #2 Hereditary haemochromatosis – Wikipedia

  https://en.wikipedia.org/wiki/Hereditary_haemochromatosis

  Hereditary haemochromatosis type 1 (HFE-related haemochromatosis) is a genetic disorder characterized by excessive intestinal absorption of dietary iron, resulting in a pathological increase in total body iron stores. […] There are five types of hereditary hemochromatosis: type 1, 2 (2A, 2B), 3, 4 and 5, all caused by mutated genes. Hereditary hemochromatosis type 1 is the most frequent, and uniquely related to the HFE gene. […] The disease follows an autosomal recessive pattern of inheritance, meaning that an individual must inherit two copies of the mutated gene involved in each cell to develop the condition. […] Disease-causing genetic variants of the HFE gene account for 90% of the cases of non-transfusion iron overload. […] The C282Y allele is a transition point mutation from guanine to adenine at nucleotide 845 in HFE, resulting in a missense mutation that replaces the cysteine residue at position 282 with a tyrosine amino acid.

• #2 Hereditary Hemochromatosis – Hematology and Oncology – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hematology-and-oncology/iron-overload/hereditary-hemochromatosis

  Hereditary hemochromatosis is a genetic disorder characterized by excessive iron (Fe) accumulation that results in tissue damage. There are 4 types of hereditary hemochromatosis, types 1 through 4, depending on the gene that is mutated. Type 1: Mutations of the HFE (human homeostatic iron regulator) gene. Type 2A and type 2B (juvenile hemochromatosis): Mutations in the HJV (type 2A, hemojuvelin BMP co-receptor) and HAMP (type 2B, hepcidin antimicrobial peptide) genes. Type 3: Mutations in the TFR2 (transferrin receptor 2) gene. Type 4A and type 4B (ferroportin disease): Mutations in the SLC40A1 (solute carrier family 40 member 1) gene in both types 4A (diminished export function of ferroportin) and 4B (resistance of ferroportin to hepcidin). Other much rarer genetic disorders can cause hepatic iron overload, but the clinical picture is usually dominated by symptoms and signs due to failure of other organs. Although these types vary markedly in age of onset, clinical consequences of iron overload are the same in all types. Type 1a is classic hereditary hemochromatosis, also termed HFE-related hemochromatosis, and more than 80% of cases are caused by the homozygous C282Y mutation. Type 1b hemochromatosis is caused by C282Y/H63D compound heterozygote mutations and results in clinically significant iron overload in only 0.5 to 2% of affected individuals. The disorder is autosomal recessive, with a homozygous frequency of 1:200 and a heterozygous frequency of 1:8 in people of Northern European ancestry. The C282Y and H63D mutations are uncommon among people with African ancestry and rare among people with Asian ancestry. Of patients with clinical features of hemochromatosis, 83% are homozygous. However, for unknown reasons, phenotypic (clinical) disease is much less common than predicted by the frequency of the gene. Type 2 hereditary hemochromatosis is a rare autosomal recessive disorder caused by mutations in the HJV gene that affect the transcription protein hemojuvelin (type 2A), or mutations in the HAMP gene, which directly codes for hepcidin, a peptide hormone made in the liver and involved in iron homeostasis (type 2B). Type 3 hereditary hemochromatosis occurs due to mutations in transferrin receptor 2 (TFR2) gene that codes for a protein that appears to control saturation of transferrin. Type 4 hereditary hemochromatosis occurs largely in people of southern European ancestry. It results from an autosomal dominant mutation in the SLC40A1 gene and affects the ability of ferroportin, an iron-transport protein, to bind hepcidin. In type 4A disease, hepcidin production is normal but the export function of ferroportin is reduced, leading to intracellular iron retention and low plasma iron levels, normal or low transferrin saturation, and elevated serum ferritin levels. In type 4B disease, there is resistance of ferroportin to hepcidin leading to iron overload because ferroportin does not respond to hepcidin’s regulatory effects, causing excessive iron export from cells into the plasma. The clinical consequences of iron overload tend to be similar regardless of the etiology and pathophysiology of the overload.

• #2 Hemochromatosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/177216-overview

  Hereditary hemochromatosis is a genetic heterogeneous disorder inherited as an autosomal recessive trait. The gene is tightly linked to the human leukocyte antigen (HLA)-A region on the short arm of chromosome 6. HFE, a specific gene for hemochromatosis, has been identified. […] Homozygosity for a missense mutation, with substitution of a cysteine residue for a tyrosine residue at amino acid position 282 (C282Y) of HFE is found in 70-100% of clinically diagnosed patients. A second missense mutation, with substitution of histidine for aspartate at amino acid 63 (H63D), has also been identified. The clinical effects of this mutation appear to be limited. […] C282Y homozygotes and, possibly, C282Y/H63D compound heterozygotes, appear to be at risk for clinical iron overload. The precise mechanism by which mutations in the HFE gene lead to iron overload is unknown. The outcome is increased intestinal iron absorption and predominantly hepatocellular accumulation of hepatic iron. […] Evidence indicates that certain forms of hereditary hemochromatosis are caused by hepcidin deficiency. Studies suggest that TfR2 is a modulator of hepcidin production in response to iron; hepcidin was low or undetectable in most cases of patients homozygous for TfR2 mutation.

• #2 Hereditary hemochromatosis: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/hereditary-hemochromatosis/

  Hereditary hemochromatosis is a disorder that causes the body to absorb too much iron from the diet. […] Mutations in several genes can cause hereditary hemochromatosis. Type 1 hemochromatosis results from mutations in the HFE gene, and type 2 hemochromatosis results from mutations in either the HJV or HAMP gene. Mutations in the TFR2 gene cause type 3 hemochromatosis, and mutations in the SLC40A1 gene cause type 4 hemochromatosis. […] The proteins produced from these genes play important roles in regulating the absorption, transport, and storage of iron in the body. Mutations in any of these genes impair the control of the intestine’s absorption of iron from foods during digestion and alter the distribution of iron to other parts of the body. As a result, iron accumulates in tissues and organs, which can disrupt their normal functions.

• #2 Hemochromatosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430862/

  Type 4 hereditary hemochromatosis is the only known type to be inherited in an autosomal dominant fashion. […] Causes of secondary hemochromatosis include erythropoietic hemochromatosis, a condition that results from excess iron absorption because the patient is producing excessive amounts of red blood cells. […] Excessive iron consumption can also cause hemochromatosis. Historically, this has resulted from drinking beer prepared in steel drums. Accidental and intentional overdoses of iron can result from the consumption of some over-the-counter dietary supplements.

• #2 Hemochromatosis (Iron Overload): Causes, Symptoms, Treatment, Diet & More

  https://my.clevelandclinic.org/health/diseases/14971-hemochromatosis-iron-overload

  Hemochromatosis, or iron overload, is a condition in which your body stores too much iron. Its often genetic. […] An inherited genetic change is the most common cause. Its called primary hemochromatosis, hereditary hemochromatosis or classical hemochromatosis. With primary hemochromatosis, problems with the DNA come from both parents and cause the body to absorb too much iron. […] In secondary hemochromatosis, medical treatments or other medical conditions cause the iron overload. Examples include: Anemia (low amount of red blood cells), Blood transfusions, Iron pills or injections, Kidney dialysis over a long period of time, Liver disease, such as hepatitis C infection or fatty liver disease. […] The inherited form of hemochromatosis is more common in white people with ancestors from Northern Europe. […] Other factors that increase the chances of developing hemochromatosis include alcohol abuse and a family history of: Arthritis, Diabetes, Heart attack, Erectile dysfunction, Liver disease.

• #2 Secondary Hemochromatosis: Symptoms, Causes, Treatment, and Outlook

  https://www.healthline.com/health/secondary-hemochromatosis

  Secondary hemochromatosis is when iron builds up in your tissue due to an underlying medical condition and not due to your genetics. […] Its most commonly caused by chronic blood transfusions used to treat conditions that cause low red blood cell counts. […] The most common cause of secondary hemochromatosis is chronic blood transfusions. […] Other potential causes of secondary hemochromatosis are: increased iron absorption by your intestines due to the ineffective production of red blood cells, iron poisoning from iron supplements or other sources of iron, underlying conditions such as cirrhosis, steatohepatitis, porphyria cutanea tarda, advanced hepatitis B or hepatitis C. […] Very rarely, excess dietary iron intake can lead to secondary hemochromatosis. […] Secondary hemochromatosis is more common in children than primary hemochromatosis.

• #2 Patient education: Hereditary hemochromatosis (Beyond the Basics) – UpToDate

  https://www.uptodate.com/contents/hereditary-hemochromatosis-beyond-the-basics/print

  In fact, most people do not develop iron overload even if the HFE C282Y variant is inherited from both parents. The reasons some people develop iron overload and some do not are still being studied. […] […] Risk factors — In the United States, approximately 5 in every 1000 people of European ancestry (0.5 percent) have hereditary hemochromatosis, although some are unaware of it. Relatives of people with the HFE C282Y variant should undergo testing since they may have the variant without knowing it. […] […] Iron overload is more likely to be seen in males than in females and at a younger age in males than females.

• #2

  https://www.nhs.uk/conditions/haemochromatosis/causes/

  Haemochromatosis is caused by a faulty gene that can be passed on to a child by their parents. […] Most cases are linked to a fault in a gene called HFE, which affects your ability to absorb iron from food. […] You’re only at risk of haemochromatosis if you inherit the faulty HFE gene from both of your parents. […] If you only inherit the faulty gene from 1 parent, you’ll be at risk of passing it on to your children known as being a „carrier” but you will not develop haemochromatosis yourself. […] But inheriting 2 copies of the faulty gene does not mean you’ll definitely get haemochromatosis. […] For unknown reasons, only a small proportion of people with 2 copies of the faulty HFE gene will ever develop the condition.

• #2

  https://www.nhs.uk/conditions/haemochromatosis/

  Haemochromatosis is caused by a faulty gene that affects how the body absorbs iron from your diet. […] You’re at risk of developing the condition if both of your parents have this faulty gene and you inherit 1 copy from each of them. […] You will not get haemochromatosis if you only inherit 1 copy of the faulty gene but there’s a chance you could pass the faulty gene on to any children you have. […] If you do inherit 2 copies, you will not necessarily get haemochromatosis. Only a small number of people with 2 copies of this faulty gene will ever develop the condition. It’s not known exactly why this is.

• #2 Hereditary Hemochromatosis

  https://ketteringhealth.org/conditions/hereditary-hemochromatosis/

  Hereditary hemochromatosis is a genetic disease. This means it is passed down from parents through their genes. It is most common in white people whose families are from Northern Europe. Men and women are equally affected by the disease. Hereditary hemochromatosis is one of the most common genetic disorders in the U.S. […] You may be born with this condition if you inherit two hemochromatosis genes, one from each parent. If you have only one of these genes, you are called a carrier of the gene. You don’t have symptoms. But you have a greater chance of having a child with this disease. […] If parents without hemochromatosis have a child with the disorder, there is a 25% chance that any additional child may be born with the disease. Parents, children, and siblings (first-degree relatives) of people with hemochromatosis should be screened for the disorder.

• #2 Hemochromatosis // Middlesex Health

  https://middlesexhealth.org/learning-center/diseases-and-conditions/hemochromatosis

  Many people have gene changes that cause hemochromatosis. However, not everyone develops iron overload to a degree that causes tissue and organ damage. […] Hereditary hemochromatosis isn’t the only type of hemochromatosis. Other types include: Juvenile hemochromatosis. This causes the same problems in young people that hereditary hemochromatosis causes in adults. But iron buildup begins much earlier, and symptoms usually appear between the ages of 15 and 30. This condition is caused by changes in the hemojuvelin or hepcidin genes. […] Neonatal hemochromatosis. In this serious disease, iron builds up quickly in the liver of the developing baby in the womb. It is thought to be an autoimmune disease, in which the body attacks itself. […] Secondary hemochromatosis. This form of the disease is not inherited and is often referred to as iron overload. People with certain types of anemia or liver disease may often need multiple blood transfusions. This can lead to excess iron buildup.

• #2 Symptoms & Causes of Hemochromatosis – NIDDK

  https://www.niddk.nih.gov/health-information/liver-disease/hemochromatosis/symptoms-causes

  Mutations in genes that control how the body absorbs iron cause primary hemochromatosis. The most common mutations are in the HFE genes and are called C282Y and H63D. […] The important HFE mutations are autosomal recessive, meaning that a person must inherit two copies of the HFE gene with the mutation to have hemochromatosis. […] Mutations in other genes that control how the body manages iron levels cause 10 to 15 percent of cases of primary hemochromatosis. […] Secondary hemochromatosis is caused by excessive iron in the diet or from multiple blood transfusions. […] The usual cause of secondary hemochromatosis is blood transfusions given for severe types of anemia, such as sickle cell disease or thalassemias. […] Iron overload from excess iron in the diet is very rare but can be caused by cooking and brewing alcohol in crude iron pots or skillets. […] Neonatal hemochromatosis occurs when a pregnant woman’s immune system produces antibodies that damage the liver of a fetus, causing iron overload.

• #2 Haemochromatosis

  https://www.chemeurope.com/en/encyclopedia/Haemochromatosis.html

  Transfusion hemosiderosis is the accumulation of iron, mainly in the liver, in patients who receive frequent blood transfusions (such as those with thalassemia). […] Dyserythropoeisis, also known as myelodysplastic syndrome is a disorder in the production of red blood cells. This leads to increased iron recycling from the bone marrow and accumulation in the liver. […] The regulation of how much iron enters the body from food is complex, and each year brings new discoveries about the numerous factors working in harmony to bring about balance in the metabolism of iron in humans. […] Other genes whose mutations have been associated with iron overload include the autosomal dominant SLC11A3/ferroportin 1 gene and TfR2 (transferrin receptor 2). These mutations, and the iron overload they cause, are much rarer than HFE-haemochromatosis. […] Recently, a new unifying theory for the pathogenesis of hereditary hemochromatosis has been proposed that focuses on the hepcidin-ferroportin regulatory axis. Inappropriately low levels of hepcidin, the iron regulatory hormone, can account for the clinical phenotype of iron overload.

• #2 Hereditary Haemochromatosis (Causes, Symptoms, and Treatment)

  https://patient.info/doctor/hereditary-haemochromatosis

  HHC is a relatively common genetic disorder in northern European populations and is probably under-diagnosed. […] Haemochromatosis is inherited in an autosomal recessive pattern but the clinical picture is more complex because the expression (penetrance) of the gene varies. This means that not everyone who is homozygous for HHC genes will develop clinical disease. The variation in gene expression may be due to other factors affecting iron accumulation. […] There are rarer forms of inherited haemochromatosis, where patients have 'classical’ clinical features of haemochromatosis but lack mutations in the HFE gene. […] Juvenile haemochromatosis is an inherited condition in which there is clinical onset in the second or third decade. The gene responsible is probably located on chromosome 1.

• #2 Genetic condition haemochromatosis linked to higher levels of disease in older people – News

  https://news.exeter.ac.uk/faculty-of-health-and-life-sciences/genetic-condition-haemochromatosis-linked-to-higher-levels-of-disease-in-older-people/

  These findings highlight the need for earlier diagnosis of iron overload, as many people with the high risk genetic variants are currently diagnosed too late to prevent organ damage. […] This important data supports the long-held belief that we should be using targeted genetic testing more consistently to make an earlier and more accurate diagnosis of haemochromatosis.

• #2 Hemochromatosis: Types, Risk Factors, and Causes

  https://www.healthline.com/health/hemochromatosis

  Primary hemochromatosis, also known as hereditary hemochromatosis, usually results from genetic factors. […] The HFE gene, or hemochromatosis gene, controls how much iron you absorb from food. […] Usually, a person with hereditary hemochromatosis inherits a copy of the defective gene from each parent. […] However, not everyone who inherits the genes develops the illness. Researchers are looking into why some people have symptoms of iron overload and others do not. […] Secondary hemochromatosis occurs when a buildup of iron stems from another medical condition, such as erythropoietic hemochromatosis. […] Other risk factors for secondary hemochromatosis include: alcohol dependency, a family history of diabetes, heart disease, or liver disease, taking iron or vitamin C supplements, which can increase the amount of iron the body absorbs, frequent blood transfusions.

• #2 About Hereditary Hemochromatosis | Hereditary Hemochromatosis | CDC

  https://www.cdc.gov/hereditary-hemochromatosis/about/index.html

  Hereditary hemochromatosis is most commonly caused by certain changes in a specific gene, called the HFE gene. If you inherit two of these genetic changes (mutations), one from each parent, you have hereditary hemochromatosis and are at risk for developing high iron levels. […] However, most people with hereditary hemochromatosis never develop symptoms or complications. […] If you have a family member, especially a sibling, who is known to have hereditary hemochromatosis, talk to your healthcare provider about genetic testing.

• #3 Iron overload – Wikipedia

  https://en.wikipedia.org/wiki/Iron_overload

  Iron overload (also known as haemochromatosis or hemochromatosis) is the abnormal and increased accumulation of total iron in the body, leading to organ damage. The primary mechanism of organ damage is oxidative stress, as elevated intracellular iron levels increase free radical formation via the Fenton reaction. Iron overload is often primary (i.e. hereditary haemochromatosis) but may also be secondary to repeated blood transfusions (i.e. transfusional iron overload). […] The term hemochromatosis was initially used to refer to what is now more specifically called hemochromatosis type 1 (or HFE-related hereditary hemochromatosis). Currently, hemochromatosis (without further specification) is mostly defined as iron overload with a hereditary or primary cause, or originating from a metabolic disorder. However, the term is currently also used more broadly to refer to any form of iron overload, thus requiring specification of the cause, for example, hereditary hemochromatosis.

• #3

  https://www.nhs.uk/conditions/haemochromatosis/causes/

  Haemochromatosis is caused by a faulty gene that can be passed on to a child by their parents. […] Most cases are linked to a fault in a gene called HFE, which affects your ability to absorb iron from food. […] You’re only at risk of haemochromatosis if you inherit the faulty HFE gene from both of your parents. […] If you only inherit the faulty gene from 1 parent, you’ll be at risk of passing it on to your children known as being a „carrier” but you will not develop haemochromatosis yourself. […] But inheriting 2 copies of the faulty gene does not mean you’ll definitely get haemochromatosis. […] For unknown reasons, only a small proportion of people with 2 copies of the faulty HFE gene will ever develop the condition.

• #3 Hereditary Hemochromatosis – Hematology and Oncology – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hematology-and-oncology/iron-overload/hereditary-hemochromatosis

  Hereditary hemochromatosis is a genetic disorder characterized by excessive iron (Fe) accumulation that results in tissue damage. There are 4 types of hereditary hemochromatosis, types 1 through 4, depending on the gene that is mutated. Type 1: Mutations of the HFE (human homeostatic iron regulator) gene. Type 2A and type 2B (juvenile hemochromatosis): Mutations in the HJV (type 2A, hemojuvelin BMP co-receptor) and HAMP (type 2B, hepcidin antimicrobial peptide) genes. Type 3: Mutations in the TFR2 (transferrin receptor 2) gene. Type 4A and type 4B (ferroportin disease): Mutations in the SLC40A1 (solute carrier family 40 member 1) gene in both types 4A (diminished export function of ferroportin) and 4B (resistance of ferroportin to hepcidin). Other much rarer genetic disorders can cause hepatic iron overload, but the clinical picture is usually dominated by symptoms and signs due to failure of other organs. Although these types vary markedly in age of onset, clinical consequences of iron overload are the same in all types. Type 1a is classic hereditary hemochromatosis, also termed HFE-related hemochromatosis, and more than 80% of cases are caused by the homozygous C282Y mutation. Type 1b hemochromatosis is caused by C282Y/H63D compound heterozygote mutations and results in clinically significant iron overload in only 0.5 to 2% of affected individuals. The disorder is autosomal recessive, with a homozygous frequency of 1:200 and a heterozygous frequency of 1:8 in people of Northern European ancestry. The C282Y and H63D mutations are uncommon among people with African ancestry and rare among people with Asian ancestry. Of patients with clinical features of hemochromatosis, 83% are homozygous. However, for unknown reasons, phenotypic (clinical) disease is much less common than predicted by the frequency of the gene. Type 2 hereditary hemochromatosis is a rare autosomal recessive disorder caused by mutations in the HJV gene that affect the transcription protein hemojuvelin (type 2A), or mutations in the HAMP gene, which directly codes for hepcidin, a peptide hormone made in the liver and involved in iron homeostasis (type 2B). Type 3 hereditary hemochromatosis occurs due to mutations in transferrin receptor 2 (TFR2) gene that codes for a protein that appears to control saturation of transferrin. Type 4 hereditary hemochromatosis occurs largely in people of southern European ancestry. It results from an autosomal dominant mutation in the SLC40A1 gene and affects the ability of ferroportin, an iron-transport protein, to bind hepcidin. In type 4A disease, hepcidin production is normal but the export function of ferroportin is reduced, leading to intracellular iron retention and low plasma iron levels, normal or low transferrin saturation, and elevated serum ferritin levels. In type 4B disease, there is resistance of ferroportin to hepcidin leading to iron overload because ferroportin does not respond to hepcidin’s regulatory effects, causing excessive iron export from cells into the plasma. The clinical consequences of iron overload tend to be similar regardless of the etiology and pathophysiology of the overload.

• #3 Hereditary haemochromatosis – Wikipedia

  https://en.wikipedia.org/wiki/Hereditary_haemochromatosis

  Hereditary haemochromatosis type 1 (HFE-related haemochromatosis) is a genetic disorder characterized by excessive intestinal absorption of dietary iron, resulting in a pathological increase in total body iron stores. […] There are five types of hereditary hemochromatosis: type 1, 2 (2A, 2B), 3, 4 and 5, all caused by mutated genes. Hereditary hemochromatosis type 1 is the most frequent, and uniquely related to the HFE gene. […] The disease follows an autosomal recessive pattern of inheritance, meaning that an individual must inherit two copies of the mutated gene involved in each cell to develop the condition. […] Disease-causing genetic variants of the HFE gene account for 90% of the cases of non-transfusion iron overload. […] The C282Y allele is a transition point mutation from guanine to adenine at nucleotide 845 in HFE, resulting in a missense mutation that replaces the cysteine residue at position 282 with a tyrosine amino acid.

• #3 Hemochromatosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/177216-overview

  Hereditary hemochromatosis is a genetic heterogeneous disorder inherited as an autosomal recessive trait. The gene is tightly linked to the human leukocyte antigen (HLA)-A region on the short arm of chromosome 6. HFE, a specific gene for hemochromatosis, has been identified. […] Homozygosity for a missense mutation, with substitution of a cysteine residue for a tyrosine residue at amino acid position 282 (C282Y) of HFE is found in 70-100% of clinically diagnosed patients. A second missense mutation, with substitution of histidine for aspartate at amino acid 63 (H63D), has also been identified. The clinical effects of this mutation appear to be limited. […] C282Y homozygotes and, possibly, C282Y/H63D compound heterozygotes, appear to be at risk for clinical iron overload. The precise mechanism by which mutations in the HFE gene lead to iron overload is unknown. The outcome is increased intestinal iron absorption and predominantly hepatocellular accumulation of hepatic iron. […] Evidence indicates that certain forms of hereditary hemochromatosis are caused by hepcidin deficiency. Studies suggest that TfR2 is a modulator of hepcidin production in response to iron; hepcidin was low or undetectable in most cases of patients homozygous for TfR2 mutation.

• #3 Hereditary Haemochromatosis (Causes, Symptoms, and Treatment)

  https://patient.info/doctor/hereditary-haemochromatosis

  Hereditary haemochromatosis (HHC) is a heterogeneous group of disorders related to deficiency of the iron regulatory hormone hepcidin. HHC is an autosomal recessive genetic disease in which increased intestinal absorption of iron causes accumulation in tissues, especially the liver, which may lead to organ damage. […] Defects of the HFE gene (located on the short arm of chromosome 6) cause the majority of cases of inherited haemochromatosis, which is therefore often referred to as HFE haemochromatosis (HFE-HC). […] A systematic review has shown that about 0.4% of people of northern European descent have the genetic mutation that increases the risk of developing haemochromatosis but the clinical penetrance of the mutation is much lower than the genetic prevalence. […] The known mutations of the HFE gene are C282Y and H63D. The C282Y mutation is most common in white populations.

• #3 Hemochromatosis (Iron Overload): Causes, Symptoms, Treatment, Diet & More

  https://my.clevelandclinic.org/health/diseases/14971-hemochromatosis-iron-overload

  Hemochromatosis, or iron overload, is a condition in which your body stores too much iron. Its often genetic. […] An inherited genetic change is the most common cause. Its called primary hemochromatosis, hereditary hemochromatosis or classical hemochromatosis. With primary hemochromatosis, problems with the DNA come from both parents and cause the body to absorb too much iron. […] In secondary hemochromatosis, medical treatments or other medical conditions cause the iron overload. Examples include: Anemia (low amount of red blood cells), Blood transfusions, Iron pills or injections, Kidney dialysis over a long period of time, Liver disease, such as hepatitis C infection or fatty liver disease. […] The inherited form of hemochromatosis is more common in white people with ancestors from Northern Europe. […] Other factors that increase the chances of developing hemochromatosis include alcohol abuse and a family history of: Arthritis, Diabetes, Heart attack, Erectile dysfunction, Liver disease.

• #3 Secondary Hemochromatosis: Symptoms, Causes, Treatment, and Outlook

  https://www.healthline.com/health/secondary-hemochromatosis

  Secondary hemochromatosis is when iron builds up in your tissue due to an underlying medical condition and not due to your genetics. […] Its most commonly caused by chronic blood transfusions used to treat conditions that cause low red blood cell counts. […] The most common cause of secondary hemochromatosis is chronic blood transfusions. […] Other potential causes of secondary hemochromatosis are: increased iron absorption by your intestines due to the ineffective production of red blood cells, iron poisoning from iron supplements or other sources of iron, underlying conditions such as cirrhosis, steatohepatitis, porphyria cutanea tarda, advanced hepatitis B or hepatitis C. […] Very rarely, excess dietary iron intake can lead to secondary hemochromatosis. […] Secondary hemochromatosis is more common in children than primary hemochromatosis.

• #3 Patient education: Hereditary hemochromatosis (Beyond the Basics) – UpToDate

  https://www.uptodate.com/contents/hereditary-hemochromatosis-beyond-the-basics/print

  In fact, most people do not develop iron overload even if the HFE C282Y variant is inherited from both parents. The reasons some people develop iron overload and some do not are still being studied. […] […] Risk factors — In the United States, approximately 5 in every 1000 people of European ancestry (0.5 percent) have hereditary hemochromatosis, although some are unaware of it. Relatives of people with the HFE C282Y variant should undergo testing since they may have the variant without knowing it. […] […] Iron overload is more likely to be seen in males than in females and at a younger age in males than females.

• #3 Haemochromatosis

  https://www.chemeurope.com/en/encyclopedia/Haemochromatosis.html

  Transfusion hemosiderosis is the accumulation of iron, mainly in the liver, in patients who receive frequent blood transfusions (such as those with thalassemia). […] Dyserythropoeisis, also known as myelodysplastic syndrome is a disorder in the production of red blood cells. This leads to increased iron recycling from the bone marrow and accumulation in the liver. […] The regulation of how much iron enters the body from food is complex, and each year brings new discoveries about the numerous factors working in harmony to bring about balance in the metabolism of iron in humans. […] Other genes whose mutations have been associated with iron overload include the autosomal dominant SLC11A3/ferroportin 1 gene and TfR2 (transferrin receptor 2). These mutations, and the iron overload they cause, are much rarer than HFE-haemochromatosis. […] Recently, a new unifying theory for the pathogenesis of hereditary hemochromatosis has been proposed that focuses on the hepcidin-ferroportin regulatory axis. Inappropriately low levels of hepcidin, the iron regulatory hormone, can account for the clinical phenotype of iron overload.

• #4 Hemochromatosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430862/

  Hemochromatosis is a disorder characterized by excessive iron accumulation in body tissues that leads to the dysfunction of various organs. […] Hereditary hemochromatosis, the most common form, is an autosomal recessive disorder predominantly found in individuals of European descent. The disorder is caused by mutations in HFE, resulting in increased iron absorption. […] Type 1 hereditary hemochromatosis occurs in patients who are typically homozygous for loss-of-function mutations in HFE. These mutations cause increased iron absorption despite an average dietary iron intake. […] Type 2 hereditary hemochromatosis is also inherited in an autosomal recessive fashion without a predilection for either sex. […] Type 3 hereditary hemochromatosis, also inherited in an autosomal recessive fashion, has a typical age of onset of 30 to 40 years. This type is due to mutations in the transferrin-receptor gene (TFR2) on chromosome 7.

• #4 Hemochromatosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/177216-overview

  Hereditary hemochromatosis is a genetic heterogeneous disorder inherited as an autosomal recessive trait. The gene is tightly linked to the human leukocyte antigen (HLA)-A region on the short arm of chromosome 6. HFE, a specific gene for hemochromatosis, has been identified. […] Homozygosity for a missense mutation, with substitution of a cysteine residue for a tyrosine residue at amino acid position 282 (C282Y) of HFE is found in 70-100% of clinically diagnosed patients. A second missense mutation, with substitution of histidine for aspartate at amino acid 63 (H63D), has also been identified. The clinical effects of this mutation appear to be limited. […] C282Y homozygotes and, possibly, C282Y/H63D compound heterozygotes, appear to be at risk for clinical iron overload. The precise mechanism by which mutations in the HFE gene lead to iron overload is unknown. The outcome is increased intestinal iron absorption and predominantly hepatocellular accumulation of hepatic iron. […] Evidence indicates that certain forms of hereditary hemochromatosis are caused by hepcidin deficiency. Studies suggest that TfR2 is a modulator of hepcidin production in response to iron; hepcidin was low or undetectable in most cases of patients homozygous for TfR2 mutation.

• #4

  https://www.nhs.uk/conditions/haemochromatosis/causes/

  Haemochromatosis is caused by a faulty gene that can be passed on to a child by their parents. […] Most cases are linked to a fault in a gene called HFE, which affects your ability to absorb iron from food. […] You’re only at risk of haemochromatosis if you inherit the faulty HFE gene from both of your parents. […] If you only inherit the faulty gene from 1 parent, you’ll be at risk of passing it on to your children known as being a „carrier” but you will not develop haemochromatosis yourself. […] But inheriting 2 copies of the faulty gene does not mean you’ll definitely get haemochromatosis. […] For unknown reasons, only a small proportion of people with 2 copies of the faulty HFE gene will ever develop the condition.

• #4 Hemochromatosis (Iron Overload): Causes, Symptoms, Treatment, Diet & More

  https://my.clevelandclinic.org/health/diseases/14971-hemochromatosis-iron-overload

  Hemochromatosis, or iron overload, is a condition in which your body stores too much iron. Its often genetic. […] An inherited genetic change is the most common cause. Its called primary hemochromatosis, hereditary hemochromatosis or classical hemochromatosis. With primary hemochromatosis, problems with the DNA come from both parents and cause the body to absorb too much iron. […] In secondary hemochromatosis, medical treatments or other medical conditions cause the iron overload. Examples include: Anemia (low amount of red blood cells), Blood transfusions, Iron pills or injections, Kidney dialysis over a long period of time, Liver disease, such as hepatitis C infection or fatty liver disease. […] The inherited form of hemochromatosis is more common in white people with ancestors from Northern Europe. […] Other factors that increase the chances of developing hemochromatosis include alcohol abuse and a family history of: Arthritis, Diabetes, Heart attack, Erectile dysfunction, Liver disease.

• #4 Hereditary Haemochromatosis (Causes, Symptoms, and Treatment)

  https://patient.info/doctor/hereditary-haemochromatosis

  Hereditary haemochromatosis (HHC) is a heterogeneous group of disorders related to deficiency of the iron regulatory hormone hepcidin. HHC is an autosomal recessive genetic disease in which increased intestinal absorption of iron causes accumulation in tissues, especially the liver, which may lead to organ damage. […] Defects of the HFE gene (located on the short arm of chromosome 6) cause the majority of cases of inherited haemochromatosis, which is therefore often referred to as HFE haemochromatosis (HFE-HC). […] A systematic review has shown that about 0.4% of people of northern European descent have the genetic mutation that increases the risk of developing haemochromatosis but the clinical penetrance of the mutation is much lower than the genetic prevalence. […] The known mutations of the HFE gene are C282Y and H63D. The C282Y mutation is most common in white populations.

• #4 Hereditary Hemochromatosis – Hematology and Oncology – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hematology-and-oncology/iron-overload/hereditary-hemochromatosis

  Hereditary hemochromatosis is a genetic disorder characterized by excessive iron (Fe) accumulation that results in tissue damage. There are 4 types of hereditary hemochromatosis, types 1 through 4, depending on the gene that is mutated. Type 1: Mutations of the HFE (human homeostatic iron regulator) gene. Type 2A and type 2B (juvenile hemochromatosis): Mutations in the HJV (type 2A, hemojuvelin BMP co-receptor) and HAMP (type 2B, hepcidin antimicrobial peptide) genes. Type 3: Mutations in the TFR2 (transferrin receptor 2) gene. Type 4A and type 4B (ferroportin disease): Mutations in the SLC40A1 (solute carrier family 40 member 1) gene in both types 4A (diminished export function of ferroportin) and 4B (resistance of ferroportin to hepcidin). Other much rarer genetic disorders can cause hepatic iron overload, but the clinical picture is usually dominated by symptoms and signs due to failure of other organs. Although these types vary markedly in age of onset, clinical consequences of iron overload are the same in all types. Type 1a is classic hereditary hemochromatosis, also termed HFE-related hemochromatosis, and more than 80% of cases are caused by the homozygous C282Y mutation. Type 1b hemochromatosis is caused by C282Y/H63D compound heterozygote mutations and results in clinically significant iron overload in only 0.5 to 2% of affected individuals. The disorder is autosomal recessive, with a homozygous frequency of 1:200 and a heterozygous frequency of 1:8 in people of Northern European ancestry. The C282Y and H63D mutations are uncommon among people with African ancestry and rare among people with Asian ancestry. Of patients with clinical features of hemochromatosis, 83% are homozygous. However, for unknown reasons, phenotypic (clinical) disease is much less common than predicted by the frequency of the gene. Type 2 hereditary hemochromatosis is a rare autosomal recessive disorder caused by mutations in the HJV gene that affect the transcription protein hemojuvelin (type 2A), or mutations in the HAMP gene, which directly codes for hepcidin, a peptide hormone made in the liver and involved in iron homeostasis (type 2B). Type 3 hereditary hemochromatosis occurs due to mutations in transferrin receptor 2 (TFR2) gene that codes for a protein that appears to control saturation of transferrin. Type 4 hereditary hemochromatosis occurs largely in people of southern European ancestry. It results from an autosomal dominant mutation in the SLC40A1 gene and affects the ability of ferroportin, an iron-transport protein, to bind hepcidin. In type 4A disease, hepcidin production is normal but the export function of ferroportin is reduced, leading to intracellular iron retention and low plasma iron levels, normal or low transferrin saturation, and elevated serum ferritin levels. In type 4B disease, there is resistance of ferroportin to hepcidin leading to iron overload because ferroportin does not respond to hepcidin’s regulatory effects, causing excessive iron export from cells into the plasma. The clinical consequences of iron overload tend to be similar regardless of the etiology and pathophysiology of the overload.

• #4 Haemochromatosis

  https://www.chemeurope.com/en/encyclopedia/Haemochromatosis.html

  Transfusion hemosiderosis is the accumulation of iron, mainly in the liver, in patients who receive frequent blood transfusions (such as those with thalassemia). […] Dyserythropoeisis, also known as myelodysplastic syndrome is a disorder in the production of red blood cells. This leads to increased iron recycling from the bone marrow and accumulation in the liver. […] The regulation of how much iron enters the body from food is complex, and each year brings new discoveries about the numerous factors working in harmony to bring about balance in the metabolism of iron in humans. […] Other genes whose mutations have been associated with iron overload include the autosomal dominant SLC11A3/ferroportin 1 gene and TfR2 (transferrin receptor 2). These mutations, and the iron overload they cause, are much rarer than HFE-haemochromatosis. […] Recently, a new unifying theory for the pathogenesis of hereditary hemochromatosis has been proposed that focuses on the hepcidin-ferroportin regulatory axis. Inappropriately low levels of hepcidin, the iron regulatory hormone, can account for the clinical phenotype of iron overload.

• #5 Hemochromatosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430862/

  Hemochromatosis is a disorder characterized by excessive iron accumulation in body tissues that leads to the dysfunction of various organs. […] Hereditary hemochromatosis, the most common form, is an autosomal recessive disorder predominantly found in individuals of European descent. The disorder is caused by mutations in HFE, resulting in increased iron absorption. […] Type 1 hereditary hemochromatosis occurs in patients who are typically homozygous for loss-of-function mutations in HFE. These mutations cause increased iron absorption despite an average dietary iron intake. […] Type 2 hereditary hemochromatosis is also inherited in an autosomal recessive fashion without a predilection for either sex. […] Type 3 hereditary hemochromatosis, also inherited in an autosomal recessive fashion, has a typical age of onset of 30 to 40 years. This type is due to mutations in the transferrin-receptor gene (TFR2) on chromosome 7.

• #5 Hemochromatosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/177216-overview

  Hereditary hemochromatosis is a genetic heterogeneous disorder inherited as an autosomal recessive trait. The gene is tightly linked to the human leukocyte antigen (HLA)-A region on the short arm of chromosome 6. HFE, a specific gene for hemochromatosis, has been identified. […] Homozygosity for a missense mutation, with substitution of a cysteine residue for a tyrosine residue at amino acid position 282 (C282Y) of HFE is found in 70-100% of clinically diagnosed patients. A second missense mutation, with substitution of histidine for aspartate at amino acid 63 (H63D), has also been identified. The clinical effects of this mutation appear to be limited. […] C282Y homozygotes and, possibly, C282Y/H63D compound heterozygotes, appear to be at risk for clinical iron overload. The precise mechanism by which mutations in the HFE gene lead to iron overload is unknown. The outcome is increased intestinal iron absorption and predominantly hepatocellular accumulation of hepatic iron. […] Evidence indicates that certain forms of hereditary hemochromatosis are caused by hepcidin deficiency. Studies suggest that TfR2 is a modulator of hepcidin production in response to iron; hepcidin was low or undetectable in most cases of patients homozygous for TfR2 mutation.

• #5 Hemochromatosis (Iron Overload): Causes, Symptoms, Treatment, Diet & More

  https://my.clevelandclinic.org/health/diseases/14971-hemochromatosis-iron-overload

  Hemochromatosis, or iron overload, is a condition in which your body stores too much iron. Its often genetic. […] An inherited genetic change is the most common cause. Its called primary hemochromatosis, hereditary hemochromatosis or classical hemochromatosis. With primary hemochromatosis, problems with the DNA come from both parents and cause the body to absorb too much iron. […] In secondary hemochromatosis, medical treatments or other medical conditions cause the iron overload. Examples include: Anemia (low amount of red blood cells), Blood transfusions, Iron pills or injections, Kidney dialysis over a long period of time, Liver disease, such as hepatitis C infection or fatty liver disease. […] The inherited form of hemochromatosis is more common in white people with ancestors from Northern Europe. […] Other factors that increase the chances of developing hemochromatosis include alcohol abuse and a family history of: Arthritis, Diabetes, Heart attack, Erectile dysfunction, Liver disease.

• #6 Hemochromatosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/177216-overview

  Hereditary hemochromatosis is a genetic heterogeneous disorder inherited as an autosomal recessive trait. The gene is tightly linked to the human leukocyte antigen (HLA)-A region on the short arm of chromosome 6. HFE, a specific gene for hemochromatosis, has been identified. […] Homozygosity for a missense mutation, with substitution of a cysteine residue for a tyrosine residue at amino acid position 282 (C282Y) of HFE is found in 70-100% of clinically diagnosed patients. A second missense mutation, with substitution of histidine for aspartate at amino acid 63 (H63D), has also been identified. The clinical effects of this mutation appear to be limited. […] C282Y homozygotes and, possibly, C282Y/H63D compound heterozygotes, appear to be at risk for clinical iron overload. The precise mechanism by which mutations in the HFE gene lead to iron overload is unknown. The outcome is increased intestinal iron absorption and predominantly hepatocellular accumulation of hepatic iron. […] Evidence indicates that certain forms of hereditary hemochromatosis are caused by hepcidin deficiency. Studies suggest that TfR2 is a modulator of hepcidin production in response to iron; hepcidin was low or undetectable in most cases of patients homozygous for TfR2 mutation.

• #7 Hemochromatosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/177216-overview

  Hereditary hemochromatosis is a genetic heterogeneous disorder inherited as an autosomal recessive trait. The gene is tightly linked to the human leukocyte antigen (HLA)-A region on the short arm of chromosome 6. HFE, a specific gene for hemochromatosis, has been identified. […] Homozygosity for a missense mutation, with substitution of a cysteine residue for a tyrosine residue at amino acid position 282 (C282Y) of HFE is found in 70-100% of clinically diagnosed patients. A second missense mutation, with substitution of histidine for aspartate at amino acid 63 (H63D), has also been identified. The clinical effects of this mutation appear to be limited. […] C282Y homozygotes and, possibly, C282Y/H63D compound heterozygotes, appear to be at risk for clinical iron overload. The precise mechanism by which mutations in the HFE gene lead to iron overload is unknown. The outcome is increased intestinal iron absorption and predominantly hepatocellular accumulation of hepatic iron. […] Evidence indicates that certain forms of hereditary hemochromatosis are caused by hepcidin deficiency. Studies suggest that TfR2 is a modulator of hepcidin production in response to iron; hepcidin was low or undetectable in most cases of patients homozygous for TfR2 mutation.

Zobacz więcej