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. Normally, iron absorption is tightly regulated, but in hemochromatosis, the body absorbs too much iron, which it cannot excrete. 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. Excess iron is deposited in organs, including the liver, pancreas, heart, and skin, often leading to conditions such as liver disease, diabetes, heart failure, and skin discoloration, known as „bronze diabetes.” The types of hereditary hemochromatosis vary based on genetic mutations. Type 1 is the most common, while types 2, 3, and 4 are rarer variants. Secondary hemochromatosis can occur due to frequent blood transfusions or certain hematological disorders.

• #2 Hemochromatosis | Arthritis Foundation

  https://www.arthritis.org/diseases/hemochromatosis

  Hemochromatosis, or iron overload disease, is one of the most common inherited disorders. Hereditary hemochromatosis, sometimes called iron overload disease, causes the body to absorb too much iron from foods. Hemochromatosis is caused by a genetic mutation in a gene called HFE. About 70 percent of those who inherit two abnormal genes develop hemochromatosis. One of two common mutations in the HFE gene is found in 85 percent of people who have hereditary hemochromatosis. Hemochromatosis symptoms often occur earlier in men than women, and men may experience more severe symptoms of the disease related to organ damage, such as diabetes, loss of sex drive or impotence or heart failure. Treatment for hemochromatosis involves removing blood from the body, as is done when donating blood, to reduce iron levels. Returning iron to normal levels relieves the fatigue and most symptoms of hemochromatosis; it also prevents complications from occurring, but it can’t repair the damage already done.

• #3

  https://www.beaumont.org/conditions/hemochromatosis

  Hereditary hemochromatosis is one of the most common genetic disorders in the U.S. […] Hemochromatosis is a genetic disease, often most prevalent among people who are white. Genetic means that hemochromatosis is inherited. A person will be born with hemochromatosis if two hemochromatosis genes are inherited–one from the mother and one from the father. […] According to the CDC, more than 1 million people in the U.S. have the gene mutation that can cause hemochromatosis. […] Although hemochromatosis is an autosomal recessive disorder (which usually means men and women are equally affected), iron overload from hereditary hemochromatosis is more common in men than women.

• #4 Hemochromatosis – StatPearls – NCBI Bookshelf

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

  Retained iron is primarily deposited in the parenchymal cells in hereditary hemochromatosis, whereas transfusional hemochromatosis predominately results in iron deposition in the reticuloendothelial cells. The excess iron is deposited in the cells as hemosiderin, eventually leading to cell death and replacement of these cells by a fibrous deposition that causes destruction or impairment of organ function. Hereditary hemochromatosis is traditionally classified into 4 classes or types with some additional subtypes. […] 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. While more than 100 HFE mutations can cause Type 1 hereditary hemochromatosis, the most common mutation is the p.Cys282Tyr or C282Y variant; the second most common mutation is the p.His63Asp or H63D mutation. HFE is present on the short arm of chromosome 6 (6p21.3). The resultant anomaly is a decreased hepcidin production or a state of hepcidin resistance. This is considered the classic form of hereditary hemochromatosis, is inherited in an autosomal recessive fashion, and disproportionately affects males.

• #5 Hemochromatosis – StatPearls – NCBI Bookshelf

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

  Retained iron is primarily deposited in the parenchymal cells in hereditary hemochromatosis, whereas transfusional hemochromatosis predominately results in iron deposition in the reticuloendothelial cells. The excess iron is deposited in the cells as hemosiderin, eventually leading to cell death and replacement of these cells by a fibrous deposition that causes destruction or impairment of organ function. Hereditary hemochromatosis is traditionally classified into 4 classes or types with some additional subtypes. […] 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. While more than 100 HFE mutations can cause Type 1 hereditary hemochromatosis, the most common mutation is the p.Cys282Tyr or C282Y variant; the second most common mutation is the p.His63Asp or H63D mutation. HFE is present on the short arm of chromosome 6 (6p21.3). The resultant anomaly is a decreased hepcidin production or a state of hepcidin resistance. This is considered the classic form of hereditary hemochromatosis, is inherited in an autosomal recessive fashion, and disproportionately affects males.

• #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 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. […] 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. […] However, carriers may experience iron overload themselves at a later stage if certain factors come into play. […] 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.

• #8 Hemochromatosis – StatPearls – NCBI Bookshelf

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

  Retained iron is primarily deposited in the parenchymal cells in hereditary hemochromatosis, whereas transfusional hemochromatosis predominately results in iron deposition in the reticuloendothelial cells. The excess iron is deposited in the cells as hemosiderin, eventually leading to cell death and replacement of these cells by a fibrous deposition that causes destruction or impairment of organ function. Hereditary hemochromatosis is traditionally classified into 4 classes or types with some additional subtypes. […] 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. While more than 100 HFE mutations can cause Type 1 hereditary hemochromatosis, the most common mutation is the p.Cys282Tyr or C282Y variant; the second most common mutation is the p.His63Asp or H63D mutation. HFE is present on the short arm of chromosome 6 (6p21.3). The resultant anomaly is a decreased hepcidin production or a state of hepcidin resistance. This is considered the classic form of hereditary hemochromatosis, is inherited in an autosomal recessive fashion, and disproportionately affects males.

• #9 Hemochromatosis – StatPearls – NCBI Bookshelf

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

  Retained iron is primarily deposited in the parenchymal cells in hereditary hemochromatosis, whereas transfusional hemochromatosis predominately results in iron deposition in the reticuloendothelial cells. The excess iron is deposited in the cells as hemosiderin, eventually leading to cell death and replacement of these cells by a fibrous deposition that causes destruction or impairment of organ function. Hereditary hemochromatosis is traditionally classified into 4 classes or types with some additional subtypes. […] 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. While more than 100 HFE mutations can cause Type 1 hereditary hemochromatosis, the most common mutation is the p.Cys282Tyr or C282Y variant; the second most common mutation is the p.His63Asp or H63D mutation. HFE is present on the short arm of chromosome 6 (6p21.3). The resultant anomaly is a decreased hepcidin production or a state of hepcidin resistance. This is considered the classic form of hereditary hemochromatosis, is inherited in an autosomal recessive fashion, and disproportionately affects males.

• #10 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.

• #11 Hereditary Hemochromatosis (Iron Overload) Causes & Symptoms

  https://www.medicinenet.com/iron_overload/article.htm

  Hereditary hemochromatosis is an inherited (genetic) disorder in which there is excessive accumulation of iron in the body (iron overload). […] In individuals with hereditary hemochromatosis, the daily absorption of iron from the intestines is greater than the amount needed to replace losses. […] There are primarily two mutations associated with hereditary hemochromatosis; C282Y and H63D. […] A C282Y homozygote is a person who has inherited one mutated C282Y gene from each parent. […] A C282Y/H63D compound heterozygote is a person who has inherited one mutated C282Y gene from one parent and a second mutated H63D gene from the other parent. […] Most compound heterozygotes have normal iron levels though some can develop mild to moderate iron overload. […] A C282Y heterozygote is a person who has inherited one mutated C282Y gene from one parent and a second normal HFE gene from the other parent.

• #12 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. 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. In transferrin deficiency, absorbed iron that enters the portal system not bound to transferrin is deposited in the liver. In ceruloplasmin deficiency, lack of ferroxidase causes defective conversion of Fe2+ to Fe3+. The mechanism for iron overload in both HFE and non-HFE hemochromatosis is increased iron absorption from the gastrointestinal tract, leading to chronic deposition of iron in the tissues. Hemochromatosis types 1 through 4 share the same pathogenic basis and key clinical features.

• #13 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. […] Each patient with the susceptible genotype accumulates iron at different rates depending on iron intake, the exact nature of the genetic variant, and the presence of other insults to the liver, such as alcohol and viral disease.

• #14 Hereditary Hemochromatosis | AAFP

  https://www.aafp.org/pubs/afp/issues/2013/0201/p183.html

  Hereditary hemochromatosis is more common in white populations of northern European origin and is highest in Ireland; the prevalence ranges from one in 150 to 250 persons. […] However, because only 10 percent (one in 2,500) of those with C282Y homozygosity present with end-organ damage or clinical manifestations of hereditary hemochromatosis, most persons who are positive for hereditary hemochromatosis are asymptomatic. […] The diagnosis of hereditary hemochromatosis requires increased iron stores, with or without symptoms. […] C282Y homozygosity in the absence of elevated iron stores is not diagnostic for hereditary hemochromatosis, although such persons would have genetic susceptibility of developing it in the future. […] All patients with homozygous hereditary hemochromatosis and evidence of iron overload (i.e., transferrin saturation greater than 45 percent and serum ferritin level greater than 300 ng per mL in men and greater than 200 ng per mL in women) should be treated, regardless of symptoms. […] Although randomized controlled trials have not been performed, the standard of care is phlebotomy to reduce total body iron levels and achieve normal ferritin levels.

• #15 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. […] Hemochromatosis refers to a genetic disorder characterized by excess iron in the body. Excess iron can build up in organs and can damage them. Without treatment, the iron overload causes these organs to stop working properly, which can lead to death if not treated. […] 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.

• #16 Hemochromatosis – StatPearls – NCBI Bookshelf

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

  Type 2 hereditary hemochromatosis is also inherited in an autosomal recessive fashion without a predilection for either sex. Historically, this disease was referred to as „juvenile” hemochromatosis, and the typical age of onset is in adolescence or early adulthood (15 to 20 years). Type 2 hereditary hemochromatosis has 2 subtypes, 2a and 2b. Type 2a is due to a mutation in the gene initially referred to as hemojuvelin but now known as HFE2. Type 2b is due to mutations in the hepcidin antimicrobial peptide (HAMP) gene on chromosome 19. […] 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. […] Type 4 hereditary hemochromatosis is the only known type to be inherited in an autosomal dominant fashion. Historically, this subtype was known as ferroportin disease, as the relevant mutations occur in the ferroportin transport protein known as ferroportin/solute carrier family 40 member 1, encoded by SCL40A1 on chromosome 2. The age of onset of type 4 hemochromatosis is highly variable and may be as early as 10 years or as late as 80 years.

• #17 Hemochromatosis – StatPearls – NCBI Bookshelf

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

  Type 2 hereditary hemochromatosis is also inherited in an autosomal recessive fashion without a predilection for either sex. Historically, this disease was referred to as „juvenile” hemochromatosis, and the typical age of onset is in adolescence or early adulthood (15 to 20 years). Type 2 hereditary hemochromatosis has 2 subtypes, 2a and 2b. Type 2a is due to a mutation in the gene initially referred to as hemojuvelin but now known as HFE2. Type 2b is due to mutations in the hepcidin antimicrobial peptide (HAMP) gene on chromosome 19. […] 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. […] Type 4 hereditary hemochromatosis is the only known type to be inherited in an autosomal dominant fashion. Historically, this subtype was known as ferroportin disease, as the relevant mutations occur in the ferroportin transport protein known as ferroportin/solute carrier family 40 member 1, encoded by SCL40A1 on chromosome 2. The age of onset of type 4 hemochromatosis is highly variable and may be as early as 10 years or as late as 80 years.

• #18 Hemochromatosis – StatPearls – NCBI Bookshelf

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

  Type 2 hereditary hemochromatosis is also inherited in an autosomal recessive fashion without a predilection for either sex. Historically, this disease was referred to as „juvenile” hemochromatosis, and the typical age of onset is in adolescence or early adulthood (15 to 20 years). Type 2 hereditary hemochromatosis has 2 subtypes, 2a and 2b. Type 2a is due to a mutation in the gene initially referred to as hemojuvelin but now known as HFE2. Type 2b is due to mutations in the hepcidin antimicrobial peptide (HAMP) gene on chromosome 19. […] 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. […] Type 4 hereditary hemochromatosis is the only known type to be inherited in an autosomal dominant fashion. Historically, this subtype was known as ferroportin disease, as the relevant mutations occur in the ferroportin transport protein known as ferroportin/solute carrier family 40 member 1, encoded by SCL40A1 on chromosome 2. The age of onset of type 4 hemochromatosis is highly variable and may be as early as 10 years or as late as 80 years.

• #19 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. 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. In transferrin deficiency, absorbed iron that enters the portal system not bound to transferrin is deposited in the liver. In ceruloplasmin deficiency, lack of ferroxidase causes defective conversion of Fe2+ to Fe3+. The mechanism for iron overload in both HFE and non-HFE hemochromatosis is increased iron absorption from the gastrointestinal tract, leading to chronic deposition of iron in the tissues. Hemochromatosis types 1 through 4 share the same pathogenic basis and key clinical features.

• #20 Hemochromatosis – StatPearls – NCBI Bookshelf

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

  Type 2 hereditary hemochromatosis is also inherited in an autosomal recessive fashion without a predilection for either sex. Historically, this disease was referred to as „juvenile” hemochromatosis, and the typical age of onset is in adolescence or early adulthood (15 to 20 years). Type 2 hereditary hemochromatosis has 2 subtypes, 2a and 2b. Type 2a is due to a mutation in the gene initially referred to as hemojuvelin but now known as HFE2. Type 2b is due to mutations in the hepcidin antimicrobial peptide (HAMP) gene on chromosome 19. […] 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. […] Type 4 hereditary hemochromatosis is the only known type to be inherited in an autosomal dominant fashion. Historically, this subtype was known as ferroportin disease, as the relevant mutations occur in the ferroportin transport protein known as ferroportin/solute carrier family 40 member 1, encoded by SCL40A1 on chromosome 2. The age of onset of type 4 hemochromatosis is highly variable and may be as early as 10 years or as late as 80 years.

• #21 Hemochromatosis – StatPearls – NCBI Bookshelf

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

  Type 2 hereditary hemochromatosis is also inherited in an autosomal recessive fashion without a predilection for either sex. Historically, this disease was referred to as „juvenile” hemochromatosis, and the typical age of onset is in adolescence or early adulthood (15 to 20 years). Type 2 hereditary hemochromatosis has 2 subtypes, 2a and 2b. Type 2a is due to a mutation in the gene initially referred to as hemojuvelin but now known as HFE2. Type 2b is due to mutations in the hepcidin antimicrobial peptide (HAMP) gene on chromosome 19. […] 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. […] Type 4 hereditary hemochromatosis is the only known type to be inherited in an autosomal dominant fashion. Historically, this subtype was known as ferroportin disease, as the relevant mutations occur in the ferroportin transport protein known as ferroportin/solute carrier family 40 member 1, encoded by SCL40A1 on chromosome 2. The age of onset of type 4 hemochromatosis is highly variable and may be as early as 10 years or as late as 80 years.

• #22 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. 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. In transferrin deficiency, absorbed iron that enters the portal system not bound to transferrin is deposited in the liver. In ceruloplasmin deficiency, lack of ferroxidase causes defective conversion of Fe2+ to Fe3+. The mechanism for iron overload in both HFE and non-HFE hemochromatosis is increased iron absorption from the gastrointestinal tract, leading to chronic deposition of iron in the tissues. Hemochromatosis types 1 through 4 share the same pathogenic basis and key clinical features.

• #23 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. This iron builds up in parts like the skin, heart, liver, pancreas, and joints. Since the body cant get rid of extra iron, these parts can get damaged. […] The main causes of hemochromatosis are because of genetics. Certain gene changes lead to this condition. Its important to know about these genes early on. This helps in detecting the disorder sooner and managing it well. […] 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. This extra iron can build up in the bodys organs and tissues.

• #24 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. This iron builds up in parts like the skin, heart, liver, pancreas, and joints. Since the body cant get rid of extra iron, these parts can get damaged. […] The main causes of hemochromatosis are because of genetics. Certain gene changes lead to this condition. Its important to know about these genes early on. This helps in detecting the disorder sooner and managing it well. […] 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. This extra iron can build up in the bodys organs and tissues.

• #25 Hemochromatosis – StatPearls – NCBI Bookshelf

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

  Retained iron is primarily deposited in the parenchymal cells in hereditary hemochromatosis, whereas transfusional hemochromatosis predominately results in iron deposition in the reticuloendothelial cells. The excess iron is deposited in the cells as hemosiderin, eventually leading to cell death and replacement of these cells by a fibrous deposition that causes destruction or impairment of organ function. Hereditary hemochromatosis is traditionally classified into 4 classes or types with some additional subtypes. […] 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. While more than 100 HFE mutations can cause Type 1 hereditary hemochromatosis, the most common mutation is the p.Cys282Tyr or C282Y variant; the second most common mutation is the p.His63Asp or H63D mutation. HFE is present on the short arm of chromosome 6 (6p21.3). The resultant anomaly is a decreased hepcidin production or a state of hepcidin resistance. This is considered the classic form of hereditary hemochromatosis, is inherited in an autosomal recessive fashion, and disproportionately affects males.

• #26 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.

• #27 Hemochromatosis – StatPearls – NCBI Bookshelf

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

  Retained iron is primarily deposited in the parenchymal cells in hereditary hemochromatosis, whereas transfusional hemochromatosis predominately results in iron deposition in the reticuloendothelial cells. The excess iron is deposited in the cells as hemosiderin, eventually leading to cell death and replacement of these cells by a fibrous deposition that causes destruction or impairment of organ function. Hereditary hemochromatosis is traditionally classified into 4 classes or types with some additional subtypes. […] 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. While more than 100 HFE mutations can cause Type 1 hereditary hemochromatosis, the most common mutation is the p.Cys282Tyr or C282Y variant; the second most common mutation is the p.His63Asp or H63D mutation. HFE is present on the short arm of chromosome 6 (6p21.3). The resultant anomaly is a decreased hepcidin production or a state of hepcidin resistance. This is considered the classic form of hereditary hemochromatosis, is inherited in an autosomal recessive fashion, and disproportionately affects males.

• #28 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.

• #29 Pathogenesis, Diagnosis, and Clinical Implications of Hereditary Hemochromatosis—The Cardiological Point of View

  https://www.mdpi.com/2075-4418/11/7/1279

  Hereditary hemochromatosis (HH) is a genetic disease leading to excessive iron absorption, its accumulation, and oxidative stress induction causing different organ damage, including the heart. […] This heterogeneous group of iron overload disorders is caused by mutations in various genes encoding proteins involved in iron homeostasis. […] More than 80% of HH cases are related to homozygosity for the C282Y mutation in the HFE gene. […] Genetic testing enables to detection of HH at an early stage and, consequently, to start treatment early enough to stop the alterations in different organs, including the heart. […] The heart is mentioned among organs most charged with iron in various animal models of hemochromatosis. […] It is known that systemic Hepc insufficiency causes hyperabsorption of dietary iron, hyperferremia, and tissue iron overload, which are hallmarks of HH.

• #30 Hemochromatosis – StatPearls – NCBI Bookshelf

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

  Retained iron is primarily deposited in the parenchymal cells in hereditary hemochromatosis, whereas transfusional hemochromatosis predominately results in iron deposition in the reticuloendothelial cells. The excess iron is deposited in the cells as hemosiderin, eventually leading to cell death and replacement of these cells by a fibrous deposition that causes destruction or impairment of organ function. Hereditary hemochromatosis is traditionally classified into 4 classes or types with some additional subtypes. […] 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. While more than 100 HFE mutations can cause Type 1 hereditary hemochromatosis, the most common mutation is the p.Cys282Tyr or C282Y variant; the second most common mutation is the p.His63Asp or H63D mutation. HFE is present on the short arm of chromosome 6 (6p21.3). The resultant anomaly is a decreased hepcidin production or a state of hepcidin resistance. This is considered the classic form of hereditary hemochromatosis, is inherited in an autosomal recessive fashion, and disproportionately affects males.

• #31 What Is Hereditary Hemochromatosis?

  https://www.icliniq.com/articles/blood-health/hereditary-hemochromatosis

  Hereditary hemochromatosis is a genetic defect that leads to the deposition of iron in organs, causing dysfunction. […] The main cause of hereditary hemochromatosis is a mutation of the hemochromatosis gene (HFE) protein. A mutation in the HFE gene leads to increased iron absorption despite a normal dietary intake. H63D and C28Y are the most common mutations of the HFE gene. […] The retained iron is primarily deposited in the parenchymal cells in cases of hereditary hemochromatosis, whereas in cases of transfusional hemochromatosis, it is deposited in the reticuloendothelial cells. This excess iron is deposited in the cells as hemosiderin which eventually leads to cell death and replacement of the cells by a fibrous deposition which leads to impairment or destruction of organs. […] Hemochromatosis is commonly caused by a mutation in a certain gene. The gene affected in this condition is the hemochromatosis gene (HFE) protein, which affects the body’s ability to absorb iron from food. If a person inherits the two of defected gene variants from each parent, there is a high chance that he or she may develop hereditary hemochromatosis and be at risk for developing high iron levels. […] Certain factors that may increase the risk of hemochromatosis include — People belonging to Northern Europe are more prone to hereditary hemochromatosis than people of other ethnic backgrounds. Moreover, hemochromatosis is less common in people of black, Hispanic, and Asian ancestry.

• #32 Hemochromatosis – StatPearls – NCBI Bookshelf

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

  Retained iron is primarily deposited in the parenchymal cells in hereditary hemochromatosis, whereas transfusional hemochromatosis predominately results in iron deposition in the reticuloendothelial cells. The excess iron is deposited in the cells as hemosiderin, eventually leading to cell death and replacement of these cells by a fibrous deposition that causes destruction or impairment of organ function. Hereditary hemochromatosis is traditionally classified into 4 classes or types with some additional subtypes. […] 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. While more than 100 HFE mutations can cause Type 1 hereditary hemochromatosis, the most common mutation is the p.Cys282Tyr or C282Y variant; the second most common mutation is the p.His63Asp or H63D mutation. HFE is present on the short arm of chromosome 6 (6p21.3). The resultant anomaly is a decreased hepcidin production or a state of hepcidin resistance. This is considered the classic form of hereditary hemochromatosis, is inherited in an autosomal recessive fashion, and disproportionately affects males.

• #33 What Is Hereditary Hemochromatosis?

  https://www.icliniq.com/articles/blood-health/hereditary-hemochromatosis

  Hereditary hemochromatosis is a genetic defect that leads to the deposition of iron in organs, causing dysfunction. […] The main cause of hereditary hemochromatosis is a mutation of the hemochromatosis gene (HFE) protein. A mutation in the HFE gene leads to increased iron absorption despite a normal dietary intake. H63D and C28Y are the most common mutations of the HFE gene. […] The retained iron is primarily deposited in the parenchymal cells in cases of hereditary hemochromatosis, whereas in cases of transfusional hemochromatosis, it is deposited in the reticuloendothelial cells. This excess iron is deposited in the cells as hemosiderin which eventually leads to cell death and replacement of the cells by a fibrous deposition which leads to impairment or destruction of organs. […] Hemochromatosis is commonly caused by a mutation in a certain gene. The gene affected in this condition is the hemochromatosis gene (HFE) protein, which affects the body’s ability to absorb iron from food. If a person inherits the two of defected gene variants from each parent, there is a high chance that he or she may develop hereditary hemochromatosis and be at risk for developing high iron levels. […] Certain factors that may increase the risk of hemochromatosis include — People belonging to Northern Europe are more prone to hereditary hemochromatosis than people of other ethnic backgrounds. Moreover, hemochromatosis is less common in people of black, Hispanic, and Asian ancestry.

• #34 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. […] 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.

• #35 Hemochromatosis – StatPearls – NCBI Bookshelf

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

  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. This often occurs due to an underlying disease of the red blood cells that causes them to be more fragile and, therefore, to have a shortened lifespan. When the cells are destroyed, their iron is deposited in the body tissues. The same mechanism is in effect in patients who receive multiple, usually chronic, transfusions of red blood cells. Other less common conditions, such as porphyria cutanea tarda, can cause iron overload. Erythropoietic hemochromatosis follows the prevalence of the underlying disease and is found in a broader range of ethnicities than the hereditary form of the disorder. Furthermore, 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.

• #36 Hemochromatosis | UCSF Department of Surgery

  https://hpbsurgery.ucsf.edu/condition/hemochromatosis

  Inherited genetic defects cause primary hemochromatosis, and mutations in the HFE gene are associated with up to 90 percent of cases. The two known mutations of HFE are C282Y and H63D. C282Y defects are the most common cause of primary hemochromatosis. […] Rare defects in other genes may also cause primary hemochromatosis. Mutations in the hemojuvelin or hepcidin genes cause juvenile hemochromatosis, a type of primary hemochromatosis. […] The most common cause of secondary hemochromatosis is frequent blood transfusions in people with severe anemia. […] Hemochromatosis that is not inherited is called secondary hemochromatosis. […] Researchers are studying the causes of neonatal hemochromatosis and believe more than one factor may lead to the disease. […] Experts previously considered neonatal hemochromatosis a type of primary hemochromatosis. However, recent studies suggest genetic defects that increase iron absorption do not cause this disease. […] Primary hemochromatosis mainly affects Caucasians of Northern European descent. […] Inherited genetic defects cause primary hemochromatosis.

• #37 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.

• #38 Hemochromatosis – StatPearls – NCBI Bookshelf

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

  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. This often occurs due to an underlying disease of the red blood cells that causes them to be more fragile and, therefore, to have a shortened lifespan. When the cells are destroyed, their iron is deposited in the body tissues. The same mechanism is in effect in patients who receive multiple, usually chronic, transfusions of red blood cells. Other less common conditions, such as porphyria cutanea tarda, can cause iron overload. Erythropoietic hemochromatosis follows the prevalence of the underlying disease and is found in a broader range of ethnicities than the hereditary form of the disorder. Furthermore, 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.

• #39 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 in the liver also occurs in persons with severe liver disease such as cirrhosis due to alcoholic liver disease or advanced forms of chronic hepatitis B or C. […] 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.

• #40 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.

• #41 What Is Hemochromatosis? Causes, Symptoms, and Treatment

  https://www.everydayhealth.com/liver-disease/hemochromatosis/

  Genetics: If a person inherits two copies of the faulty gene C28Y one from each parent there’s a higher risk for developing hemochromatosis. […] Chronic Liver Disease: Individuals with chronic liver disease, including metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease, chronic hepatitis C, and particularly alcoholic liver disease, are at an increased risk of iron overload of the liver. This type of iron accumulation is different from hereditary hemochromatosis, although it’s possible to have both hereditary hemochromatosis and another form of liver disease. […] Two rare forms of hemochromatosis, neonatal hemochromatosis and juvenile hemochromatosis, are caused by different gene mutations.

• #42 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. […] 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.

• #43 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. Its less common in people with African-American, Hispanic, Asian or American Indian descent. […] 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.

• #44 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. […] 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.

• #45 Haemochromatosis

  https://dermnetnz.org/topics/haemochromatosis

  Haemochromatosis is caused by mutations in the HFE gene with autosomal recessive inheritance. Two mutations identified in the HFE gene are C282Y and H63D. […] For an individual to have haemochromatosis they must have inherited a defective gene from each parent. […] Up to half of all patients with porphyria cutanea tarda carry at least one HFE gene mutation and this may contribute to the increased stores of liver iron seen in these patients.

• #46 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 in the liver also occurs in persons with severe liver disease such as cirrhosis due to alcoholic liver disease or advanced forms of chronic hepatitis B or C. […] 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.

• #47 Hemochromatosis: Symptoms, Causes & Treatment

  https://www.careinsurance.com/blog/health-insurance-articles/hemochromatosis-symptoms-causes-and-treatment

  Hemochromatosis is an inherited disease that is passed down generations. It causes the body to deposit excessive iron in the organs and tissues. […] Primary hemochromatosis is also known as genetic hemochromatosis, which is found in the genes of the family members. This disease is inherited, if both the parents are carriers of the hemochromatosis gene. […] Secondary hemochromatosis develops in the body when the cause of iron overload is not hereditary but the issue of erythropoietic hemochromatosis. […] Here are some of the causes that can trigger the disease of secondary hemochromatosis: Overconsumption of alcohol, Chances of hereditary diseases such as heart disorder, diabetes, etc, Iron supplements, Vitamin C or multivitamins supplements, Anaemia or transferrin saturation, Frequent blood transfusion, Chronic kidney disease (dialysis sessions for a long time), Liver disease such as fatty liver disease or hepatitis C infections.

• #48 Hemochromatosis – StatPearls – NCBI Bookshelf

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

  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. This often occurs due to an underlying disease of the red blood cells that causes them to be more fragile and, therefore, to have a shortened lifespan. When the cells are destroyed, their iron is deposited in the body tissues. The same mechanism is in effect in patients who receive multiple, usually chronic, transfusions of red blood cells. Other less common conditions, such as porphyria cutanea tarda, can cause iron overload. Erythropoietic hemochromatosis follows the prevalence of the underlying disease and is found in a broader range of ethnicities than the hereditary form of the disorder. Furthermore, 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.

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

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

  Hemochromatosis is a medical condition where people have excessive iron in the body. The most common cause is an inherited genetic change, but blood transfusions and liver disease can also lead to hemochromatosis. […] Primary hemochromatosis occurs due to an alteration of normal iron absorption, usually caused by an inherited genetic mutation. […] Inherited hemochromatosis is caused by a mutation in the hereditary Fe gene (Fe is the chemical symbol for iron), referred to as the HFE gene. The most common mutations that can cause hemochromatosis are C282Y and H63D, which are both located on the HFE gene. […] Secondary hemochromatosis occurs due to medical conditions or circumstances that lead to iron overload in the body. […] Causes of secondary hemochromatosis include frequent blood transfusions (usually as treatment for a blood disorder), kidney failure, and liver disease.

• #50 Hemochromatosis | UCSF Department of Surgery

  https://hpbsurgery.ucsf.edu/condition/hemochromatosis

  Inherited genetic defects cause primary hemochromatosis, and mutations in the HFE gene are associated with up to 90 percent of cases. The two known mutations of HFE are C282Y and H63D. C282Y defects are the most common cause of primary hemochromatosis. […] Rare defects in other genes may also cause primary hemochromatosis. Mutations in the hemojuvelin or hepcidin genes cause juvenile hemochromatosis, a type of primary hemochromatosis. […] The most common cause of secondary hemochromatosis is frequent blood transfusions in people with severe anemia. […] Hemochromatosis that is not inherited is called secondary hemochromatosis. […] Researchers are studying the causes of neonatal hemochromatosis and believe more than one factor may lead to the disease. […] Experts previously considered neonatal hemochromatosis a type of primary hemochromatosis. However, recent studies suggest genetic defects that increase iron absorption do not cause this disease. […] Primary hemochromatosis mainly affects Caucasians of Northern European descent. […] Inherited genetic defects cause primary hemochromatosis.

• #51 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 in the liver also occurs in persons with severe liver disease such as cirrhosis due to alcoholic liver disease or advanced forms of chronic hepatitis B or C. […] 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.

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

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

  Excess iron supplements or excess dietary iron is a rare cause of hemochromatosis; even with high iron intake, the body’s absorption and elimination of iron might remain near normal. […] 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 risk factors include blood disorders treated with repeated blood transfusions, such as sickle cell disease or thalassemia. Additionally, you could be at risk if you have liver disease, kidney disease, or if you take high doses of iron supplements. […] Complications of untreated hemochromatosis include damage to the liver, heart, thyroid gland, joints, and pancreas.

• #53 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).

• #54 Hereditary Hemochromatosis | AAFP

  https://www.aafp.org/pubs/afp/issues/2013/0201/p183.html

  Hereditary hemochromatosis is more common in white populations of northern European origin and is highest in Ireland; the prevalence ranges from one in 150 to 250 persons. […] However, because only 10 percent (one in 2,500) of those with C282Y homozygosity present with end-organ damage or clinical manifestations of hereditary hemochromatosis, most persons who are positive for hereditary hemochromatosis are asymptomatic. […] The diagnosis of hereditary hemochromatosis requires increased iron stores, with or without symptoms. […] C282Y homozygosity in the absence of elevated iron stores is not diagnostic for hereditary hemochromatosis, although such persons would have genetic susceptibility of developing it in the future. […] All patients with homozygous hereditary hemochromatosis and evidence of iron overload (i.e., transferrin saturation greater than 45 percent and serum ferritin level greater than 300 ng per mL in men and greater than 200 ng per mL in women) should be treated, regardless of symptoms. […] Although randomized controlled trials have not been performed, the standard of care is phlebotomy to reduce total body iron levels and achieve normal ferritin levels.

• #55 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).

• #56 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. 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. In transferrin deficiency, absorbed iron that enters the portal system not bound to transferrin is deposited in the liver. In ceruloplasmin deficiency, lack of ferroxidase causes defective conversion of Fe2+ to Fe3+. The mechanism for iron overload in both HFE and non-HFE hemochromatosis is increased iron absorption from the gastrointestinal tract, leading to chronic deposition of iron in the tissues. Hemochromatosis types 1 through 4 share the same pathogenic basis and key clinical features.

• #57 Hemochromatosis | Arthritis Foundation

  https://www.arthritis.org/diseases/hemochromatosis

  Hemochromatosis, or iron overload disease, is one of the most common inherited disorders. Hereditary hemochromatosis, sometimes called iron overload disease, causes the body to absorb too much iron from foods. Hemochromatosis is caused by a genetic mutation in a gene called HFE. About 70 percent of those who inherit two abnormal genes develop hemochromatosis. One of two common mutations in the HFE gene is found in 85 percent of people who have hereditary hemochromatosis. Hemochromatosis symptoms often occur earlier in men than women, and men may experience more severe symptoms of the disease related to organ damage, such as diabetes, loss of sex drive or impotence or heart failure. Treatment for hemochromatosis involves removing blood from the body, as is done when donating blood, to reduce iron levels. Returning iron to normal levels relieves the fatigue and most symptoms of hemochromatosis; it also prevents complications from occurring, but it can’t repair the damage already done.

• #58 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.

• #59 Hemochromatosis: Causes, Symptoms, Diagnosis & Treatment

  https://birlafertility.com/blogs/what-is-hemochromatosis/

  Women undergo iron loss during the menstruation cycle; hence, they are less likely to develop hemochromatosis than men. During pregnancy, too, women’s bodies store fewer vitamins and minerals. Men are more likely to develop symptoms of hemochromatosis by the early or late 30s. […] This type arises due to external factors or other medical conditions that cause iron overload. Causes include liver diseases, chronic alcohol intake, frequent blood transfusions, iron-loading anaemias, excessive iron supplements, and long-term kidney dialysis.

• #60 Who Is at Risk for Hemochromatosis? | Hematology-Oncology Associates of CNY

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

  Hemochromatosis is one of the most common genetic diseases in the United States. […] Inheriting two faulty HFE genes (one from each parent) is the major risk factor for hemochromatosis. […] Alcoholism is another risk factor for hemochromatosis. A family history of certain diseases and conditions also puts you at higher risk for hemochromatosis. Examples of such diseases and conditions include heart attack, liver disease, diabetes, arthritis, and erectile dysfunction (impotence).

• #61 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. Its less common in people with African-American, Hispanic, Asian or American Indian descent. […] 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.

• #62 Who Is at Risk for Hemochromatosis? | Hematology-Oncology Associates of CNY

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

  Hemochromatosis is one of the most common genetic diseases in the United States. […] Inheriting two faulty HFE genes (one from each parent) is the major risk factor for hemochromatosis. […] Alcoholism is another risk factor for hemochromatosis. A family history of certain diseases and conditions also puts you at higher risk for hemochromatosis. Examples of such diseases and conditions include heart attack, liver disease, diabetes, arthritis, and erectile dysfunction (impotence).

• #63 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. […] 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. […] However, carriers may experience iron overload themselves at a later stage if certain factors come into play. […] 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.

• #64 Causes Of Hemochromatosis: Understanding The Genetic Factors

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

  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.

• #65

  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.

• #66 Hemochromatosis // Middlesex Health

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

  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.

• #67 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. […] 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.

• #68 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.

• #69 Hereditary Hemochromatosis | AAFP

  https://www.aafp.org/pubs/afp/issues/2013/0201/p183.html

  Hereditary hemochromatosis is more common in white populations of northern European origin and is highest in Ireland; the prevalence ranges from one in 150 to 250 persons. […] However, because only 10 percent (one in 2,500) of those with C282Y homozygosity present with end-organ damage or clinical manifestations of hereditary hemochromatosis, most persons who are positive for hereditary hemochromatosis are asymptomatic. […] The diagnosis of hereditary hemochromatosis requires increased iron stores, with or without symptoms. […] C282Y homozygosity in the absence of elevated iron stores is not diagnostic for hereditary hemochromatosis, although such persons would have genetic susceptibility of developing it in the future. […] All patients with homozygous hereditary hemochromatosis and evidence of iron overload (i.e., transferrin saturation greater than 45 percent and serum ferritin level greater than 300 ng per mL in men and greater than 200 ng per mL in women) should be treated, regardless of symptoms. […] Although randomized controlled trials have not been performed, the standard of care is phlebotomy to reduce total body iron levels and achieve normal ferritin levels.

• #70 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. […] The two most common mutations of this gene are C28Y and H63D. […] 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. […] In this disease, the red blood cells release too much iron into the body because they are too fragile. […] 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.

• #71 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. […] Each patient with the susceptible genotype accumulates iron at different rates depending on iron intake, the exact nature of the genetic variant, and the presence of other insults to the liver, such as alcohol and viral disease.

• #72 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. Normally, iron absorption is tightly regulated, but in hemochromatosis, the body absorbs too much iron, which it cannot excrete. 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. Excess iron is deposited in organs, including the liver, pancreas, heart, and skin, often leading to conditions such as liver disease, diabetes, heart failure, and skin discoloration, known as „bronze diabetes.” The types of hereditary hemochromatosis vary based on genetic mutations. Type 1 is the most common, while types 2, 3, and 4 are rarer variants. Secondary hemochromatosis can occur due to frequent blood transfusions or certain hematological disorders.

• #73 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.

• #74 Hemochromatosis – StatPearls – NCBI Bookshelf

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

  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. This often occurs due to an underlying disease of the red blood cells that causes them to be more fragile and, therefore, to have a shortened lifespan. When the cells are destroyed, their iron is deposited in the body tissues. The same mechanism is in effect in patients who receive multiple, usually chronic, transfusions of red blood cells. Other less common conditions, such as porphyria cutanea tarda, can cause iron overload. Erythropoietic hemochromatosis follows the prevalence of the underlying disease and is found in a broader range of ethnicities than the hereditary form of the disorder. Furthermore, 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.

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

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

  Hemochromatosis is a medical condition where people have excessive iron in the body. The most common cause is an inherited genetic change, but blood transfusions and liver disease can also lead to hemochromatosis. […] Primary hemochromatosis occurs due to an alteration of normal iron absorption, usually caused by an inherited genetic mutation. […] Inherited hemochromatosis is caused by a mutation in the hereditary Fe gene (Fe is the chemical symbol for iron), referred to as the HFE gene. The most common mutations that can cause hemochromatosis are C282Y and H63D, which are both located on the HFE gene. […] Secondary hemochromatosis occurs due to medical conditions or circumstances that lead to iron overload in the body. […] Causes of secondary hemochromatosis include frequent blood transfusions (usually as treatment for a blood disorder), kidney failure, and liver disease.

• #76 Pathogenesis, Diagnosis, and Clinical Implications of Hereditary Hemochromatosis—The Cardiological Point of View

  https://www.mdpi.com/2075-4418/11/7/1279

  The accumulation of iron deposits occurs starting from the epicardial, then through the myocardium to the endocardial layer. […] Hypertrophy is one of the macroscopic consequences of the disease. […] The increased risk of coronary artery disease due to an increased iron level is the next cause. […] The last hypothesis assumes the possibility of autoimmune process participation as a cause of heart failure in HH. […] The essential laboratory parameter in HH assessment is NTBI level, which, due to the participation of these molecules in the generation of oxidative stress damaging the tissues, is particularly important. […] High levels of NTBI may indicate earlier initiation of appropriate treatment to avoid damage to organs, including the heart muscle. […] The appropriate treatment proved to reverse cardiac damages.

Zobacz więcej