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Encyclopedia > Haemochromatosis
Haemochromatosis
Classification & external resources
ICD-10 E83.1
ICD-9 275.0
OMIM 235200 602390 606464 604720 604653
DiseasesDB 5490
eMedicine med/975  derm/878
MeSH D006432

Haemochromatosis, also spelled hemochromatosis, is a hereditary disease characterized by improper dietary iron metabolism (making it an iron overload disorder), which causes the accumulation of iron in a number of body tissues.[1] Iron accumulation can eventually cause end organ damage, most importantly in the liver and pancreas, manifesting as liver failure and diabetes mellitus respectively. It is estimated that roughly one in every 300-400 people is affected by the disease, primarily of Northern European and especially people of Irish, Scottish, Welsh and English descent.[2] The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) is a coding of diseases and signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or diseases, as classified by the World Health Organization (WHO). ... // E00-E35 - Endocrine diseases (E00-E07) Disorders of thyroid gland (E00) Congenital iodine-deficiency syndrome (E01) Iodine-deficiency-related thyroid disorders and allied conditions (E02) Subclinical iodine-deficiency hypothyroidism (E03) Other hypothyroidism (E030) Congenital hypothyroidism with diffuse goitre (E031) Congenital hypothyroidism without goitre (E032) Hypothyroidism due to medicaments and other... The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... The Disease Bold textDatabase is a free website that provides information about the relationships between medical conditions, symptoms, and medications. ... eMedicine is an online clinical medical knowledge base that was founded in 1996. ... Medical Subject Headings (MeSH) is a huge controlled vocabulary (or metadata system) for the purpose of indexing journal articles and books in the life sciences. ... A genetic disorder, or genetic disease is a disease caused, at least in part, by the genes of the person with the disease. ... For other uses, see Iron (disambiguation). ... Structure of the coenzyme adenosine triphosphate, a central intermediate in energy metabolism. ... In medicine, iron overload disorders are diseases caused by the accumulation of iron in the body. ... For other uses, see Iron (disambiguation). ... The pancreas is a gland organ in the digestive and endocrine systems of vertebrates[2]. It is both exocrine (secreting pancreatic juice containing digestive enzymes) and endocrine (producing several important hormones, including insulin, glucagon, and somatostatin). ... For the bird, see Liver bird. ... For the disease characterized by excretion of large amounts of very dilute urine, see diabetes insipidus. ... For other uses, see Europe (disambiguation). ... This article is about the Scottish as an ethnic group. ... The Welsh are, according to Hastings (1997), an ethnic group and nation associated with Wales and the Welsh language, which is a Celtic language. ... This article is about the English as an ethnic group and nation. ...


Hereditary hemochromatosis is the concept that known, measurable genetic mutations can be passed from generation to generation and cause iron accumulation, though not all clinical iron overload is associated with known hereditary markers, and not all hereditary markers cause significant iron overload. Semantically, therefore, the condition of a hereditary mutation in the iron metabolism genetic apparatus is not synonymous with clinical iron overload, though the term “hemochromatosis” is used to encompass both these concepts. Haemochromatosis, also spelled hemochromatosis, is a hereditary disease characterized by improper processing by the body of dietary iron which causes iron to accumulate in a number of body tissues, eventually causing organ dysfunction. ...

Contents

History

The disease was first described in 1865 by Armand Trousseau in an article on diabetes in patients with changing skin color.[3] Trousseau did not connect the diabetes with iron accumulation; instead this was done by Friedrich Daniel von Recklinghausen in 1890.[4][5] Categories: Possible copyright violations ... For the disease characterized by excretion of large amounts of very dilute urine, see diabetes insipidus. ... This article is about the disease that features high blood sugar. ... For other uses, see Iron (disambiguation). ... In 1882 Frederich Daniel von Recklinghausen released a monograph which reviewed previous literature and characterized the tumors of Neurofibromatosis 1 or NF-1 as neurofibromas, consisting of an intense commingling of nerve cells and fibrous tissue ...


Signs and symptoms

Haemochromatosis is notoriously protean, i.e., it presents with symptoms that are often initially attributed to other diseases. It is also true that most people with hereditary hemochromatosis genetics never actually show signs or suffer symptoms of clinical iron overload(i.e., is clinically silent).[6] Symptoms may include:[7][8][9]

Males are usually diagnosed after their forties, and women about a decade later, owing to regular iron loss by menstruation (which ceases in menopause). Cases of iron overload have been found in young children as well. Malaise is a feeling of general discomfort or uneasiness, an out of sorts feeling, often the first indication of an infection or other disease. ... Cirrhosis is a chronic disease of the liver in which liver tissue is replaced by connective tissue, resulting in the loss of liver function. ... Hepatocellular carcinoma (HCC, also called hepatoma) is a primary malignancy (cancer) of the liver. ... This article or section does not cite its references or sources. ... Hepatomegaly is the condition of having an enlarged liver. ... Insulin resistance is the condition in which normal amounts of insulin are inadequate to produce a normal insulin response from fat, muscle and liver cells. ... For the disease characterized by excretion of large amounts of very dilute urine, see diabetes insipidus. ... The pancreas is a retroperitoneal organ that serves two functions: exocrine - it produces pancreatic juice containing digestive enzymes endocrine - it produces several important hormones Anatomy The pancreas is a retroperitoneal organ located posterior to the stomach on the posterior abdominal wall. ... For other uses, see Iron (disambiguation). ... Erectile dysfunction (ED) or impotence is a sexual dysfunction characterized by the inability to develop or maintain an erection of the penis. ... Hypogonadism is a medical term for a defect of the reproductive system which results in lack of function of the gonads (ovaries or testes). ... For other uses, see Libido (disambiguation). ... A cardiac arrhythmia, also called cardiac dysrhythmia, is a disturbance in the regular rhythm of the heartbeat. ... Pericarditis is inflammation of the sac surrounding the heart, the pericardium. ... Arthritis (from Greek arthro-, joint + -itis, inflammation; plural: arthritides) is a group of conditions where there is damage caused to the joints of the body. ... Grays Fig. ... Grays Fig. ... An x-ray of a human knee Grays Fig. ... This article does not cite its references or sources. ... For other uses, see Joint (disambiguation). ... This article discusses the way the word deaf is used and how deafness is perceived by hearing and Deaf communities. ... Dyskinesia refers to an impairment of voluntary movement. ... Parkinsonism describes the common symptoms of Parkinsons disease - tremor, rigidity, akinesia or bradykinesia and postural instability. ... Endocrinology is a branch of medicine dealing with disorders of the endocrine system and its specific secretions called hormones. ... The pancreas is a gland organ in the digestive and endocrine systems of vertebrates[2]. It is both exocrine (secreting pancreatic juice containing digestive enzymes) and endocrine (producing several important hormones, including insulin, glucagon, and somatostatin). ... This article is about the disease that features high blood sugar. ... In mammals, the adrenal glands (also known as suprarenal glands) are the triangle-shaped endocrine glands that sit on top of the kidneys; their name indicates that position (ad-, near or at + -renes, kidneys). They are chiefly responsible for regulating the stress response through the synthesis of corticosteroids and catecholamines... In medicine, adrenal insufficiency (or hypocortisolism) is the inability of the adrenal gland to produce adequate amounts of cortisol in response to stress. ... The four human parathyroid glands are adjacent to the thyroid. ... In medicine, hypocalcemia is the presence of low serum calcium levels in the blood, usually taken as less than 2. ... The pituitary gland, or hypophysis, is an endocrine gland about the size of a pea that sits in a small, bony cavity (sella turcica) covered by a dural fold (sellar diaphragm) at the base of the brain. ... Human male anatomy The testicles, known medically as testes (singular testis), are the male generative glands in animals. ... // For ovary as part of plants see ovary (plants) An ovary is an egg-producing reproductive organ found in female organisms. ... Hypogonadism is a medical term for a defect of the reproductive system which results in lack of function of the gonads (ovaries or testes). ... In biology, pigment is any material resulting in color in plant or animal cells which is the result of selective absorption. ... Categories: Possible copyright violations ... 1865 (MDCCCLXV) is a common year starting on Sunday. ... This false-colored electron micrograph shows a malaria sporozoite migrating through the midgut epithelia. ... This article does not cite its references or sources. ... Spaghetti with seafood (Spaghetti allo scoglio). ... Binomial name Murray (1926) Listeria monocytogenes is a Gram-positive bacterium, in the division Firmicutes, named for Joseph Lister. ... Binomial name Yersinia enterocolitica (Schleifstein & Coleman, 1939) Yersinia enterocolitica is a species of rod-shaped bacterium, belonging to the family Enterobacteriaceae. ... Salmonella enteritidis is a Gram negative rod-shaped bacterium linked to raw or undercooked eggs and poultry, and one of many causative agents of food poisoning. ... Binomial name Klebsiella pneumoniae (Schroeter 1886) Trevisan 1887 Klebsiella pneumoniae is a Gram-negative, nonmotile, encapsulated, lactose-fermenting, facultatively anaerobic, rod-shaped bacterium found in the normal flora of the mouth, skin, and intestines. ... Binomial name Escherichia coli T. Escherich, 1885 Escherichia coli (usually abbreviated to E. coli) is one of the main species of bacteria that live in the lower intestines of warm-blooded animals (including birds and mammals) and are necessary for the proper digestion of food. ... Binomial name Rhizopus arrhizus Rhizopus arrhizus is fungus of the family Mucoraceae, characterized by sporangiophores that arise from nodes at the point where the rhizoids are formed and by a hemispherical columella. ... Not to be confused with Mensuration. ... Menopause is the physiological cessation of menstrual cycles associated with advancing age in women. ... For other uses, see Iron (disambiguation). ...


Diagnosis

Haemochromatosis can be difficult to diagnose in the early stages. Early signs may mimic other diseases. Stiff joints, diabetes, and fatigue, for example, are common in haemochromatosis and other maladies.[13]


Imaging features

Clinically the disease may be silent, but characteristic radiological features may point to the diagnosis. The increased iron stores in the organs involved, especially in the liver and pancreas, result in characteristic findings on unenhanced CT and a decreased signal intensity at MR imaging. Haemochromatosis arthropathy includes degenerative osteoarthritis and chondrocalcinosis. The distribution of the arthropathy is distinctive, but not unique, frequently affecting the second and third metacarpophalangeal joints of the hand.[citation needed] The arthropathy can therefore be an early clue as to the diagnosis of hemochromatosis. MRI algorithms are available at research institutions to quantify the amount of iron present in the liver, therefore reducing the necessity of a liver biopsy (see below) to measure the liver iron content. As of May, 2007, this technology was only available at a few sites in the USA, but documented reports of radiographic measurements of liver iron content were becoming more common. [14] For other uses, see Iron (disambiguation). ... CT apparatus in a hospital Computed axial tomography (CAT), computer-assisted tomography, computed tomography, CT, or body section roentgenography is the process of using digital processing to generate a three-dimensional image of the internals of an object from a large series of two-dimensional X-ray images taken around... “MRI” redirects here. ... An Arthropathy is a disease of a joint. ... Osteoarthritis / Osteoarthrosis (OA, also known as degenerative arthritis, degenerative joint disease, arthrosis or in more colloquial terms wear and tear), is a condition in which low-grade inflammation results in pain in the joints, caused by wearing of the cartilage that covers and acts as a cushion inside joints. ... It has been suggested that this article or section be merged with Calcium pyrophosphate deposition disease. ... An Arthropathy is a disease of a joint. ... An Arthropathy is a disease of a joint. ... The mri are a fictional alien species in the Faded Sun Trilogy of C.J. Cherryh. ... For the bird, see Liver bird. ... A biopsy (in Greek: bios = life and opsy = look/appearance) is a medical test involving the removal of cells or tissues for examination. ... For the bird, see Liver bird. ... For other uses, see Iron (disambiguation). ... Radiography is the creation of radiographs, photographs made by exposing a photographic film or other image receptor to X-rays. ... For the bird, see Liver bird. ...


Chemistry

Serum transferrin saturation- A first step is the measurement of transferrin saturation, the protein which chemically binds to iron and carries it through the blood to the liver, spleen and bone marrow.[15] Measuring transferrin provides a measurement of iron in the blood. Saturation values of 45% are probably a good cutoff to determine whether a patient is a candidate for further testing. [16] The transferrin saturation is usually expressed as a percentage, and is calculated as the total serum iron level divided by the serum iron transferrin level times 100. Serum Ferritin- Ferritin, the protein which chemically binds to iron and stores it in the body. Measuring ferritin provides a measurement of iron in the whole body. Normal values for males are 12-300 ng/ml (nanograms per milliliter) and for female, 12-150 ng/ml. Low values indicate iron deficiency, which may be attributed to a number of causes. Higher than normal also may indicate other causes including haemochromatosis.[17][18] Other blood tests routinely performed: blood count, renal function, liver enzymes, electrolytes, glucose (and/or an oral glucose tolerance test (OGTT)). Transferrin is a plasma protein for iron ion delivery. ... For the bird, see Liver bird. ... The spleen is an organ located in the abdomen, where it functions in the destruction of old red blood cells and holding a reservoir of blood. ... This article does not cite any references or sources. ... Percent transferrin saturation is a medical laboratory value. ... The medical laboratory test for serum iron measures the amount of circulating iron that is bound to transferrin. ... Ferritin is a globular protein found mainly in the liver, which can store about 4500 iron (Fe3+)ions in a hollow protein shell made of 24 subunits. ... Iron deficiency can refer to: Iron deficiency (plant disorder) Iron deficiency (medicine) This is a disambiguation page — a navigational aid which lists other pages that might otherwise share the same title. ... A full blood count (FBC) or complete blood count (CBC) is a test requested by a doctor or other medical professional that gives information about the cells in a patients blood. ... In medicine (nephrology) renal function is an indication of the state of the kidney and its role in physiology. ... Liver function tests (LFTs or LFs), are groups of clinical biochemistry laboratory blood assays designed to give a doctor or other health professional information about the state of a patients liver. ... An electrolyte is a substance containing free ions that behaves as an electrically conductive medium. ... Glucose (Glc), a monosaccharide (or simple sugar), is an important carbohydrate in biology. ... Oral glucose tolerance test (OGTT) is a medical test that is performed to diagnose (or exclude) diabetes. ...


Functional testing

Based on the history, the doctor might consider specific tests to monitor organ dysfunction, such as an echocardiogram for heart failure, or blood glucose monitoring for patients with hemochromatosis diabetes. The echocardiogram is an ultrasound of the heart. ... This article is about the disease that features high blood sugar. ...


Histopathology

Liver biopsy - Liver biopsies involve taking a sample of tissue from the liver, using a thin needle. The amount of iron in the sample is then quantified and compared to normal, and evidence of liver damage, especially cirrhosis, measured microscopically. Formerly, this was the only way to confirm a diagnosis of hemochromatosis but measures of transferrin and ferritin along with a history are considered adequate in determining the presence of the malady. Risks of biopsy include bruising, bleeding and infection. Now, when a history and measures of transferrin or ferritin point to haemochromatosis, it is debatable whether a liver biopsy is still necessary to quantify the amount of accumulated iron.[19] Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrotic scar tissue as well as regenerative nodules, leading to progressive loss of liver function. ... A biopsy (in Greek: bios = life and opsy = look/appearance) is a medical test involving the removal of cells or tissues for examination. ...


Screening

Screening specifically means looking for a disease in people who have no symptoms. Diagnosis, on the other hand refers to testing people who have symptoms of a disease. Standard diagnostic measures for haemochromatosis, serum transferrin saturation and serum ferritin tests, are not a part of routine medical testing. Screening for hemochromatosis is recommended if the patient has a parent, child or sibling with the disease, or have any of the following signs and symptoms:[20][21] Screening, in general, is the investigation of a great number of something (for instance, people) looking for those with a particular problem or feature. ... This article is about the medical term. ... The term symptom (from the Greek syn = con/plus and pipto = fall, together meaning co-exist) has two similar meanings in the context of physical and mental health: A symptom can be a physical condition which shows that one has a particular illness or disorder (see e. ... In general, diagnosis (plural diagnoses) has two distinct dictionary definitions. ... The term symptom (from the Greek syn = con/plus and pipto = fall, together meaning co-exist) has two similar meanings in the context of physical and mental health: A symptom can be a physical condition which shows that one has a particular illness or disorder (see e. ... This article is about the medical term. ... Look up Serum in Wiktionary, the free dictionary. ... Percent transferrin saturation is a medical laboratory value. ... Look up Serum in Wiktionary, the free dictionary. ... Ferritin is a globular protein found mainly in the liver, which can store about 4500 iron (Fe3+)ions in a hollow protein shell made of 24 subunits. ... Screening, in general, is the investigation of a great number of something (for instance, people) looking for those with a particular problem or feature. ...

  • Joint disease
  • Severe fatigue
  • Heart disease
  • Elevated liver enzymes
  • Impotence
  • Diabetes

Routine screening of the general population for hereditary hemochromatosis, that is, by genetic testing, has been evaluated by the US Preventive Services Task Force (USPSTF), among other groups. The USPSTF recommended against doing genetic testing to screen the general population for hereditary hemochromatosis because the likelihood of diagnosing clinically relevant, iron accumulating hereditary hemochromatosis in a treatable patient population approaches less than 1 in 1000 unselected patients. Also, there is no evidence that doing phlebotomy to treat asymptomatic, non-iron overloaded carriers of HFE mutations has any clinical benefit. Also, genetic carriers of the disease may never manifest the symptoms of the disease, so that the potential harm of the attendant surveillance, privacy issues, unnecessary invasive work-up, and anxiety outweigh the potential benefits. [22] [23] Screening, in general, is the investigation of a great number of something (for instance, people) looking for those with a particular problem or feature. ... Bloodletting (or blood-letting, in modern medicine referred to as phlebotomy) was a popular medical practice from antiquity up to the late 19th century, involving the withdrawal of often considerable quantities of blood from a patient in the belief that this would cure or prevent illness and disease. ... HFE could refer to: In genetics, the HFE gene, In electronics, hFE stands for Forward Current Gain, in mathematics, a public key algorithm known as the Hidden Field Equations scheme, the IATA Airport Code code of Luogang Airport, Hefei, Anhui, China In System Engineering, HFE stands for Human Factors Engineering...


Differential diagnosis

There exist other causes of excess iron accumulation, which have to be considered before Haemochromatosis is diagnosed.

  • African iron overload, formerly known as Bantu siderosis, was first observed among people of African descent in Southern Africa. Originally, this was blamed on ungalvanised barrels used to store home-made beer, which led to increased oxidation and increased iron levels in the beer. Further investigation has shown that only some people drinking this sort of beer get an iron overload syndrome, and that a similar syndrome occurred in people of African descent who have had no contact with this kind of beer (e.g., African Americans). This led investigators to the discovery of a gene polymorphism in the gene for ferroportin which predisposes some people of African descent to iron overload.[24]
  • Transfusion hemosiderosis is the accumulation of iron, mainly in the liver, in patients who receive frequent blood transfusions (such as those with thalassemia).
  • Dyserythropoeisis, also known as myelodysplastic syndrome is a disorder in the production of red blood cells. This leads to increased iron recycling from the bone marrow and accumulation in the liver.

African iron overload, formerly known as Bantu siderosis, is an iron overload disorder first observed among people of African descent in Southern Africa. ... Map showing the approximate distribution of Bantu (light brown) vs. ... World map showing location of Africa A satellite composite image of Africa Africa is the worlds second_largest continent in both area and population, after Asia. ... Categories: Africa geography stubs | Southern Africa ... Galvanization, named after the Italian scientist Luigi Galvani, was originally the administration of electric shocks (in the 19th century also termed Faradism, after Michael Faraday). ... For other uses, see Beer (disambiguation). ... World map showing location of Africa A satellite composite image of Africa Africa is the worlds second_largest continent in both area and population, after Asia. ... For other uses, see Beer (disambiguation). ... African Americans, also known as Afro-Americans or black Americans, are an ethnic group in the United States of America whose ancestors, usually in predominant part, were indigenous to Sub-Saharan and West Africa. ... In biology, polymorphism can be defined as the occurrence in the same habitat of two or more forms of a trait in such frequencies that the rarer cannot be maintained by recurrent mutation alone. ... Ferroportin is a protein that transports iron from the inside of a cell to the outside of it. ... Transfusion hemosiderosis is the accumulation of iron, mainly in the liver, in patients who receive frequent blood transfusions (such as those with thalassemia or aplastic anemia). ... For the bird, see Liver bird. ... Blood transfusion is the process of transferring blood or blood-based products from one person into the circulatory system of another. ... Thalassemia (British spelling, thalassaemia) is an inherited autosomal recessive blood disease. ... This article does not cite any references or sources. ...

Epidemiology

Hemochromatosis is one of the most common inheritable genetic defects, especially in people of northern European extraction, with about 1 in 10 people carrying a mutation in one of the genes regulating iron metabolism. The prevalence of hereditary mutations in iron metabolism genes varies in different populations. In Northern Europeans it is of the order of one in 400 persons. A study of 3,011 unrelated white Australians found that 14% were heterozygous carriers of an HFE mutation, 0.5% were homozygous for an HFE mutation, and only 0.25% of the entire population had a clinically relevant iron overload syndrome. This means that most patients who are homozygous for HFE mutations will not manifest clinically relevant hemochromatosis (see genetics below).[25] Other populations probably have a lower prevalence of both the genetic mutation and the clinical disease. It is presumed, through genetic studies, that the original haemochromatosis mutation arose in a single person, possibly of Celtic ethnicity, who lived 60-70 generations ago. Around that time, when nutrition was less balanced than today, the presence of a mutant allele may have provided a natural selection reproductive advantage in maintaining sufficient iron levels in the blood. With our current balanced diets, this 'extra help' is unnecessary and indeed harmful. Northern Europe Northern Europe is the northern part of the European continent. ... This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ... For other uses, see Iron (disambiguation). ... Structure of the coenzyme adenosine triphosphate, a central intermediate in energy metabolism. ... In epidemiology, the prevalence of a disease in a statistical population is defined as the total number of cases of the disease in the population at a given time, or the total number of cases in the population, divided by the number of individuals in the population. ... This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ... Heterozygote cells are diploid or polyploid and have different alleles at a locus (position) on homologous chromosomes. ... HFE could refer to: In genetics, the HFE gene, In electronics, hFE stands for Forward Current Gain, in mathematics, a public key algorithm known as the Hidden Field Equations scheme, the IATA Airport Code code of Luogang Airport, Hefei, Anhui, China In System Engineering, HFE stands for Human Factors Engineering... Homozygote cells are diploid or polyploid and have the same alleles at a locus (position) on homologous chromosomes. ... HFE could refer to: In genetics, the HFE gene, In electronics, hFE stands for Forward Current Gain, in mathematics, a public key algorithm known as the Hidden Field Equations scheme, the IATA Airport Code code of Luogang Airport, Hefei, Anhui, China In System Engineering, HFE stands for Human Factors Engineering... For other uses, see Iron (disambiguation). ... In medicine, the term syndrome is the association of several clinically recognizable features, signs, symptoms, phenomena or characteristics which often occur together, so that the presence of one feature alerts the physician to the presence of the others. ... Homozygote cells are diploid or polyploid and have the same alleles at a locus (position) on homologous chromosomes. ... HFE could refer to: In genetics, the HFE gene, In electronics, hFE stands for Forward Current Gain, in mathematics, a public key algorithm known as the Hidden Field Equations scheme, the IATA Airport Code code of Luogang Airport, Hefei, Anhui, China In System Engineering, HFE stands for Human Factors Engineering... This article is about mutation in biology, for other meanings see: mutation (disambiguation). ... This article is about the general scientific term. ... It has been suggested that mutant be merged into this article or section. ... This article is about the European people. ... The updated USDA food pyramid, published in 2005, is a general nutrition guide for recommended food consumption for humans. ... In biology, mutations are permanent, sometimes transmissible (if the change is to a germ cell) changes to the genetic material (usually DNA or RNA). ... For other uses, see Natural selection (disambiguation). ... For other uses, see Iron (disambiguation). ...


Genetics

Haemochromatosis types 1-3 are inherited in an autosomal recessive fashion.
Haemochromatosis types 1-3 are inherited in an autosomal recessive fashion.
Haemochromatosis type 4 is inherited in an autosomal dominant fashion.

The regulation of how much iron enters the body from food is complex, and each year brings new discoveries about the numerous factors working in harmony to bring about balance in the metabolism of iron in humans One of the best-characterized genes that regulates the amount of iron absorbed from food is called HFE. The HFE gene has two common mutations, C282Y and H63D.[26] Inheriting just one of the C282Y mutations (heterozygous) makes a person a carrier who can pass this mutation onward. Carriers of one HFE mutation ordinarily do not manifest with clinically relevant iron accumulation at all. In the United States, most people with clinically measureable haemochromatosis (i.e., iron overload with or without end organ damage) have inherited two copies of C282Y — one from each parent — and are therefore homozygous for the trait. Mutations of the HFE gene account for 90% of the cases of clinical iron overload. This gene is closely linked to the HLA-A3 locus. Homozygosity for the C282Y mutation is the most prevalent condition resulting in clinical iron accumulation, although heterozygosity for C282Y/H63D mutations, so-called compound heterozygotes, is also known to cause clinical iron overload. So, both homozygotes for C282Y and compound heterozygotes for C282Y/H63D are known to have clinical iron overload and hemochromatosis. Most people with two copies of C282Y or one copy each of C282Y/H63D do not manifest clinical hemochromatosis, a phenomenon known as low incomplete penetrance. [25] Penetrance differs between different populations. Wikipedia does not yet have an article with this exact name. ... Wikipedia does not yet have an article with this exact name. ... It has been suggested that this article or section be merged into Dominance relationship. ... Image File history File links Autodominant2. ... Image File history File links Autodominant2. ... It has been suggested that this article or section be merged into Dominance relationship. ... For other uses, see Iron (disambiguation). ... Human beings are defined variously in biological, spiritual, and cultural terms, or in combinations thereof. ... For other uses, see Iron (disambiguation). ... HFE could refer to: In genetics, the HFE gene, In electronics, hFE stands for Forward Current Gain, in mathematics, a public key algorithm known as the Hidden Field Equations scheme, the IATA Airport Code code of Luogang Airport, Hefei, Anhui, China In System Engineering, HFE stands for Human Factors Engineering... HFE could refer to: In genetics, the HFE gene, In electronics, hFE stands for Forward Current Gain, in mathematics, a public key algorithm known as the Hidden Field Equations scheme, the IATA Airport Code code of Luogang Airport, Hefei, Anhui, China In System Engineering, HFE stands for Human Factors Engineering... Heterozygote cells are diploid or polyploid and have different alleles at a locus (position) on homologous chromosomes. ... HFE could refer to: In genetics, the HFE gene, In electronics, hFE stands for Forward Current Gain, in mathematics, a public key algorithm known as the Hidden Field Equations scheme, the IATA Airport Code code of Luogang Airport, Hefei, Anhui, China In System Engineering, HFE stands for Human Factors Engineering... Homozygote cells are diploid or polyploid and have the same alleles at a locus (position) on homologous chromosomes. ... It has been suggested that mutant be merged into this article or section. ... For other uses, see Gene (disambiguation). ... Genetic linkage occurs when particular alleles are inherited jointly. ... HLA region of Chromosome 6 The human leukocyte antigen system (HLA) is the name of the human major histocompatibility complex (MHC). ... Short and long arms Chromosome. ... Homozygote cells are diploid or polyploid and have the same alleles at a locus (position) on homologous chromosomes. ... It has been suggested that mutant be merged into this article or section. ... Heterozygote cells are diploid or polyploid and have different alleles at a locus (position) on homologous chromosomes. ... A homozygotes cells are diploid or polyploid and have the same alleles at a locus (position) on homologous chromosomes. ... For other uses, see Phenomena (disambiguation). ... Penetrance is a term used in genetics that describes the extent to which the properties controlled by a gene, its phenotype, will be expressed. ...


Other genes whose mutations have been associated with iron overload include the autosomal dominant SLC11A3/ferroportin 1 gene and TfR2 (transferrin receptor 2). These mutations, and the iron overload they cause, are much rarer than HFE-haemochromatosis. It has been suggested that this article or section be merged into Dominance relationship. ...


Recently, a classification has been developed (with chromosome locations):

Description OMIM Mutation Locus
Haemochromatosis type 1: "classical"-haemochromatosis 235200 HFE 6p21.3
Haemochromatosis type 2A: juvenile haemochromatosis 602390 hemojuvelin ("HJV", also known as HFE2) 1q21
Haemochromatosis type 2B: juvenile haemochromatosis 606464 hepcidin antimicrobial peptide (HAMP) or HFE2B 19q13
Haemochromatosis type 3 604720 transferrin receptor-2 (TFR2 or HFE3) 7q22
Haemochromatosis type 4 autosomal dominant haemochromatosis (all others are recessive), gene mutation 604653 ferroportin (SLC11A3) 2q32

The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... Short and long arms Chromosome. ... HFE gene (hemochromatosis) is a gene located on short arm of chromosome 6 at location 6p21. ... There are very few or no other articles that link to this one. ... HAMP (hepcidin antimicrobial peptide) is a human gene that instructs cells to manufacture a small protein called hepcidin, which was originally identified as having antimicrobial properties. ... Transferrin receptor is a carrier protein for transferrin. ... It has been suggested that this article or section be merged into Dominance relationship. ... It has been suggested that this article or section be merged into Dominance relationship. ... Ferroportin is a protein that transports iron from the inside of a cell to the outside of it. ...

Pathophysiology

The normal distribution of body iron stores
The normal distribution of body iron stores

Since the regulation of iron metabolism is still poorly understood, a clear model of how hemochromatosis operates is still not available as of May, 2007. For example, HFE is only part of the story, since many patients with mutated HFE do not manifest clinical iron overload, and some patients with iron overload have a normal HFE genotype. In general, people with abnormal iron regulatory genes do not reduce their absorption of iron in response to increased iron levels in the body. Thus the iron stores of the body increase. As they increase the iron which is initially stored as ferritin is deposited in organs as haemosiderin and this is toxic to tissue, probably at least partially by inducing oxidative stress.[27]. Iron is a pro-oxidant. Thus, hemochromatosis shares common symptomology (e.g., cirrhosis and dyskinetic symptoms) with other "pro-oxidant" diseases such as Wilson's disease, chronic manganese poisoning, and hyperuricemic syndrome in Dalmatian dogs. The latter also experience "bronzing". Image File history File links Iron_metabolism. ... Image File history File links Iron_metabolism. ... For other uses, see Iron (disambiguation). ... HFE could refer to: In genetics, the HFE gene, In electronics, hFE stands for Forward Current Gain, in mathematics, a public key algorithm known as the Hidden Field Equations scheme, the IATA Airport Code code of Luogang Airport, Hefei, Anhui, China In System Engineering, HFE stands for Human Factors Engineering... HFE could refer to: In genetics, the HFE gene, In electronics, hFE stands for Forward Current Gain, in mathematics, a public key algorithm known as the Hidden Field Equations scheme, the IATA Airport Code code of Luogang Airport, Hefei, Anhui, China In System Engineering, HFE stands for Human Factors Engineering... HFE could refer to: In genetics, the HFE gene, In electronics, hFE stands for Forward Current Gain, in mathematics, a public key algorithm known as the Hidden Field Equations scheme, the IATA Airport Code code of Luogang Airport, Hefei, Anhui, China In System Engineering, HFE stands for Human Factors Engineering... This article does not cite any references or sources. ... For other uses, see Iron (disambiguation). ... For other uses, see Iron (disambiguation). ... For other uses, see Iron (disambiguation). ... Ferritin is a globular protein found mainly in the liver, which can store about 4500 iron (Fe3+)ions in a hollow protein shell made of 24 subunits. ... Hemosiderin Image of a kidney viewed under a microscope. ... Toxic redirects here, but this is also the name of a song by Britney Spears; see Toxic (song) Look up toxic and toxicity in Wiktionary, the free dictionary. ... Biological tissue is a collection of interconnected cells that perform a similar function within an organism. ... Oxidative stress is a medical term for damage to animal or plant cells (and thereby the organs and tissues composed of those cells) caused by reactive oxygen species, which include (but are not limited to) superoxide, singlet oxygen, peroxynitrite or hydrogen peroxide. ... Pro-oxidants are chemicals that induce oxidative stress, either through creating reactive oxygen species or inhibiting antioxidant systems. ... Wilsons disease or hepatolenticular degeneration is an autosomal recessive hereditary disease, with an incidence of about 1 in 30,000 in most parts of the world and a male preponderance. ... Manganism or manganese poisoning is a toxic condition resulting from chronic exposure to manganese and first identified in 1837 by James Couper. ... Dalmatia (Croatian Dalmacija, Italian Dalmazia, Serbian Далмација) is a region of Croatia on the eastern coast of the Adriatic Sea, spreading between the island of Pag in the northwest and the Bay of Kotor in the southeast. ...


Intestinal crypt enterocytes and iron overload

The sensor pathway inside the small bowel enterocyte can be disrupted due to genetic errors in the iron regulatory apparatus. The enterocyte in the small bowel crypt must somehow sense the amount of circulating iron. Depending on this information, the enterocyte cell can regulate the quantity of iron receptors and channel proteins. If there is little iron, the enterocyte cell will express many of these proteins. If there is a lot, the cell will turn off the expression of iron transporters. In haemochromatosis, the enterocyte is somehow constantly fooled into thinking there is iron depletion. As a consequence, it overexpresses the necessary channel proteins, this leading to a massive, and unnecessary iron absorption. Details of how this process exactly works in health and disease are still being discovered as of May, 2007. These iron transport proteins are named DMT-1 (divalent metal transporter), for the luminal side of the cell, and ferroportin, the only known cellular iron exporter, for the basal side of the cell. Diagram showing the small intestine In biology the small intestine is the part of the gastrointestinal tract between the stomach and the large intestine (colon). ... Enterocyte is a type of epithelial cell of the superficial layer of the small and large intestine tissue. ... For other uses, see Iron (disambiguation). ... Enterocyte is a type of epithelial cell of the superficial layer of the small and large intestine tissue. ... For other uses, see Iron (disambiguation). ... For other uses, see Iron (disambiguation). ... In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ... For other uses, see Iron (disambiguation). ... Enterocyte is a type of epithelial cell of the superficial layer of the small and large intestine tissue. ... For other uses, see Iron (disambiguation). ... DMT1 (divalent metal transporter 1) is a transporter involved in human iron metabolism. ... Ferroportin is a protein that transports iron from the inside of a cell to the outside of it. ...


Hepcidin-ferroportin axis and iron overload

Recently, a new unifying theory for the pathogenesis of hereditary hemochromatosis has been proposed that focuses on the hepcidin-ferroportin regulatory axis. Inappropriately low levels of hepcidin, the iron regulatory hormone, can account for the clinical phenotype of iron overload. In this theory, low levels of circulating hepcidin result in higher levels of ferroportin expression in intestinal enterocytes and reticuloendothelial macrophages. As a result, this causes iron accumulation. HFE, hemojuvelin, BMP's and TFR2 are implicated in regulating hepcidin expression. Hepcidin is a recently discovered peptide, produced by the liver, that appears to be the master regulator of iron homeostasis in humans and other mammals. ... Hepcidin is a recently discovered peptide, produced by the liver, that appears to be the master regulator of iron homeostasis in humans and other mammals. ... Individuals in the mollusk species Donax variabilis show diverse coloration and patterning in their phenotypes. ... Hepcidin is a recently discovered peptide, produced by the liver, that appears to be the master regulator of iron homeostasis in humans and other mammals. ... Ferroportin is a protein that transports iron from the inside of a cell to the outside of it. ... The intestine is the portion of the alimentary canal extending from the stomach to the anus and, in humans and other mammals, consists of two segments, the small intestine and the large intestine. ... Enterocytes are epithelial cells of the superficial layer of the small and large bowel tissue. ... HFE could refer to: In genetics, the HFE gene, In electronics, hFE stands for Forward Current Gain, in mathematics, a public key algorithm known as the Hidden Field Equations scheme, the IATA Airport Code code of Luogang Airport, Hefei, Anhui, China In System Engineering, HFE stands for Human Factors Engineering... There are very few or no other articles that link to this one. ... Hepcidin is a recently discovered peptide, produced by the liver, that appears to be the master regulator of iron homeostasis in humans and other mammals. ...


End-organ damage

Iron is stored in the liver, the pancreas and the heart. Long term effects of haemochromatosis on these organs can be very serious, even fatal when untreated.[28] For example, similar to alcoholism, haemochromatosis can cause Cirrhosis of the liver. The liver is a primary storage area for iron and will naturally accumulate excess iron. Over time the liver is likely to be damaged by iron overload. Cirrhosis itself may lead to additional and more serious complications, including bleeding from dilated veins in the esophagus and stomach (varices) and severe fluid retention in the abdomen (ascites). Toxins may accumulate in the blood and eventually affect mental functioning. This can lead to confusion or even coma (hepatic encephalopathy). Alcoholism is the consumption of, or preoccupation with, alcoholic beverages to the extent that this behavior interferes with the drinkers normal personal, family, social, or work life, and may lead to physical or mental harm. ... Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrotic scar tissue as well as regenerative nodules, leading to progressive loss of liver function. ... For the bird, see Liver bird. ... The esophagus (also spelled oesophagus/Å“sophagus, Greek ), or gullet is an organ in vertebrates which consists of a muscular tube through which food passes from the pharynx to the stomach. ... In anatomy, the stomach is a bean-shaped hollow muscular organ of the gastrointestinal tract involved in the second phase of digestion, following mastication. ... Varices in general refers to distended veins. ... For the human abdomen, see human abdomen. ... In medicine, a coma (from the Greek koma, meaning deep sleep) is a profound state of unconsciousness. ... Encephalopathy literally means disease of the brain. ...


Liver cancer: Cirrhosis and haemochromatosis together will increase the risk of liver cancer. (Nearly one-third of people with haemochromatosis and cirrhosis eventually develop liver cancer.) For the bird, see Liver bird. ... Cancer is a class of diseases or disorders characterized by uncontrolled division of cells and the ability of these to spread, either by direct growth into adjacent tissue through invasion, or by implantation into distant sites by metastasis (where cancer cells are transported through the bloodstream or lymphatic system). ...


Diabetes: The pancreas which also stores iron is very important in the body’s mechanisms for sugar metabolism. Diabetes affects the way the body uses blood sugar (glucose). Diabetes is in turn the leading cause of new blindness in adults and may be involved in kidney failure and cardiovascular disease. This article is about the disease that features high blood sugar. ... The pancreas is a gland organ in the digestive and endocrine systems of vertebrates[2]. It is both exocrine (secreting pancreatic juice containing digestive enzymes) and endocrine (producing several important hormones, including insulin, glucagon, and somatostatin). ... Structure of the coenzyme adenosine triphosphate, a central intermediate in energy metabolism. ... Glucose (Glc), a monosaccharide (or simple sugar), is an important carbohydrate in biology. ... Renal failure is when the kidneys fail to function properly. ... Cardiovascular disease refers to the class of diseases that involve the heart or blood vessels (arteries and veins). ...


Congestive heart failure: If excess iron in the heart interferes with the its ability to circulate enough blood, a number of problems can occur including death. The condition may be reversible when haemochromatosis is treated and excess iron stores reduced. Congestive heart failure (CHF), also called congestive cardiac failure (CCF) or just heart failure, is a condition that can result from any structural or functional cardiac disorder that impairs the ability of the heart to fill with or pump a sufficient amount of blood throughout the body. ...


Heart arrhythmias: Arrhythmia or abnormal heart rhythms can cause heart palpitations, chest pain and light-headedness and are occasionally life threatening. This condition can often be reversed with treatment for haemochromatosis. The heart and lungs, from an older edition of Grays Anatomy. ... A cardiac arrhythmia, also called cardiac dysrhythmia, is a disturbance in the regular rhythm of the heartbeat. ...


Pigment changes: Deposits of iron in skin cells can turn skin a bronze or gray color. Natural Ultramarine pigment in powdered form. ...


Treatment

Early diagnosis is important because the late effects of iron accumulation can be wholly prevented by periodic phlebotomies (by venesection) comparable in volume to blood donations.[29] Treatment is initiated when ferritin levels reach 300 micrograms per litre (or 200 in nonpregnant premenopausal women). Venipuncture using a vacutainer. ... “Give blood” redirects here. ... Ferritin is a globular protein found mainly in the liver, which can store about 4500 iron (Fe3+)ions in a hollow protein shell made of 24 subunits. ... “Kg” redirects here. ... Menopause (also known as the Change of life or climacteric) is a stage of the human female reproductive cycle that occurs as the ovaries stop producing estrogen, causing the reproductive system to gradually shut down. ...


Every bag of blood (450-500 ml) contains 200-250 milligrams of iron. Phlebotomy (or bloodletting) is usually done at a weekly interval until ferritin levels are less than 20 micrograms per litre. After that, 1-4 donations per year are usually needed to maintain iron balance. The millilitre is the equivalent of a cubic centimetre. ... The milligram (symbol mg) is an SI unit of mass. ... Ancient Greek painting in a vase, showing a physician (iatros) bleeding a patient. ... Ferritin is a globular protein found mainly in the liver, which can store about 4500 iron (Fe3+)ions in a hollow protein shell made of 24 subunits. ...


Other parts of the treatment include:

This illustration shows where some types of diuretics act, and what they do. ... Captopril, the first ACE inhibitor ACE inhibitors, or inhibitors of Angiotensin-Converting Enzyme, are a group of pharmaceuticals that are used primarily in treatment of hypertension and congestive heart failure, in most cases as the drugs of first choice. ... Alcoholic beverages. ... This article is about the nutrient. ... This article is about the food. ... For other uses, see Iron (disambiguation). ... Cooked mussels Shellfish is a term used to describe shelled molluscs and crustaceans used as food. ... Spaghetti with seafood (Spaghetti allo scoglio). ... A bottle of tannic acid. ... For other uses, see Tea (disambiguation). ... For other uses, see Calcium (disambiguation). ... Oxalic acid (IUPAC name: ethanedioic acid, formula C2H2O4) is a dicarboxylic acid with structure (HOOC)-(COOH). ... Phytic acid (known as phytate when its salt form) is the principal storage form of phosphorus in many plant tissues, especially seeds. ...

References

  1. ^ Iron Overload and Hemochromatosis Centers for Disease Control and Prevention
  2. ^ Celtic Curse.
  3. ^ Trousseau A (1865). "Glycosurie, diabète sucré". Clinique médicale de l'Hôtel-Dieu de Paris 2: 663–98. 
  4. ^ von Recklinghausen FD (1890). "Hämochromatose". Tageblatt der Naturforschenden Versammlung 1889: 324. 
  5. ^ Biography of Daniel von Recklinghausen
  6. ^ Hemochromatosis-Diagnosis National Digestive Diseases Information Clearinghouse, National Institutes of Health, U.S. Department of Health and Human Services
  7. ^ Iron Overload and Hemochromatosis Centers for Disease Control and Prevention
  8. ^ Hemochromatosis National Digestive Diseases Information Clearinghouse, National Institutes of Health, U.S. Department of Health and Human Services
  9. ^ Hemochromatosis-Signs and Symptoms Mayo Foundation for Medical Education and Research (MFMER)
  10. ^ a b Jones H, Hedley-Whyte E (1983). "Idiopathic hemochromatosis (IHC): dementia and ataxia as presenting signs". Neurology 33 (11): 1479-83. PMID 6685241. 
  11. ^ Costello D, Walsh S, Harrington H, Walsh C (2004). "Concurrent hereditary haemochromatosis and idiopathic Parkinson's disease: a case report series". J Neurol Neurosurg Psychiatry 75 (4): 631-3. PMID 15026513. 
  12. ^ Nielsen J, Jensen L, Krabbe K (1995). "Hereditary haemochromatosis: a case of iron accumulation in the basal ganglia associated with a parkinsonian syndrome". J Neurol Neurosurg Psychiatry 59 (3): 318-21. PMID 7673967. 
  13. ^ Screening and Diagnosis
  14. ^ Tanner MA, He T, Westwood MA, Firmin DN, Pennell DJ (2006). "Multi-center validation of the transferability of the magnetic resonance T2* technique for the quantification of tissue iron". Haematologica 91 (10): 1388-91. PMID 17018390. 
  15. ^ Transferrin and Iron Transport Physiology
  16. ^ Screening and Diagnosis
  17. ^ Screening and Diagnosis
  18. ^ Ferritin Test Measuring iron in the body
  19. ^ Screening and diagnosis Mayo Foundation for Medical Education and Research (MFMER) Retrieved 18 March, 2007
  20. ^ Screening and Diagnosis Mayo Foundation for Medical Education and Research (MFMER). Retrieved 18 March, 2007
  21. ^ [http://www.annals.org/cgi/content/full/143/7/I-46 Screening for Hereditary Hemochromatosis: Recommendations from the American College of Physicians Annals of Internal Medicine (2005) 4 October, Volume 143 Issue 7. (Page I-46). American College of Physicians. Retrieved 18 March, 2007
  22. ^ (2006) "Screening for hemochromatosis: recommendation statement". Ann. Intern. Med. 145 (3): 204-8. PMID 16880462. 
  23. ^ Screening for Hemochromatosis U.S. Preventive Services Task Force (2006). Summary of Screening Recommendations and Supporting Documents. Retrieved 18 March, 2007
  24. ^ Gordeuk V, Caleffi A, Corradini E, Ferrara F, Jones R, Castro O, Onyekwere O, Kittles R, Pignatti E, Montosi G, Garuti C, Gangaidzo I, Gomo Z, Moyo V, Rouault T, MacPhail P, Pietrangelo A (2003). "Iron overload in Africans and African-Americans and a common mutation in the SCL40A1 (ferroportin 1) gene". Blood Cells Mol Dis 31 (3): 299-304. PMID 14636642. 
  25. ^ a b Olynyk J, Cullen D, Aquilia S, Rossi E, Summerville L, Powell L (1999). "A population-based study of the clinical expression of the hemochromatosis gene". N Engl J Med 341 (10): 718-24. PMID 10471457. 
  26. ^ Hemochromatosis-Causes Mayo Foundation for Medical Education and Research (MFMER) Retrieved March 12, 2007
  27. ^ Shizukuda Y, Bolan C, Nguyen T, Botello G, Tripodi D, Yau Y, Waclawiw M, Leitman S, Rosing D (2007). "Oxidative stress in asymptomatic subjects with hereditary hemochromatosis". Am J Hematol 82 (3): 249-50. PMID 16955456. 
  28. ^ Haemochromatosis Complications
  29. ^ Hemochromatosis - Treatment

See also

Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrotic scar tissue as well as regenerative nodules, leading to progressive loss of liver function. ...

External links


  Results from FactBites:
 
Haemochromatosis - Wikipedia, the free encyclopedia (1324 words)
Haemochromatosis, also spelled hemochromatosis, is a hereditary disease characterized by improper processing by the body of dietary iron which causes iron to accumulate in a number of body tissues, eventually causing organ dysfunction.
Haemochromatosis is notoriously protean, i.e., it presents with symptoms that are often initially attributed to other diseases.
When these investigations point at haemochromatosis, it is debatable whether a liver biopsy still needs to occur to quantify the amount of accumulated iron.
index.html (935 words)
Haemochromatosis tends to be under-diagnosed, partly because its symptoms are similar to those caused by a range of other illnesses.
A person with haemochromatosis is treated with venesection until iron in the blood is reduced to normal levels.
Haemochromatosis is a common inherited disorder, which causes the body to absorb more iron than usual from food.
  More results at FactBites »

 
 

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