Hemochromatosis: A disorder of iron metabolism characterized by a triad of HEMOSIDEROSIS; LIVER CIRRHOSIS; and DIABETES MELLITUS. It is caused by massive iron deposits in parenchymal cells that may develop after a prolonged increase of iron absorption. (Jablonski's Dictionary of Syndromes & Eponymic Diseases, 2d ed)Iron: A metallic element with atomic symbol Fe, atomic number 26, and atomic weight 55.85. It is an essential constituent of HEMOGLOBINS; CYTOCHROMES; and IRON-BINDING PROTEINS. It plays a role in cellular redox reactions and in the transport of OXYGEN.Pancreas: A nodular organ in the ABDOMEN that contains a mixture of ENDOCRINE GLANDS and EXOCRINE GLANDS. The small endocrine portion consists of the ISLETS OF LANGERHANS secreting a number of hormones into the blood stream. The large exocrine portion (EXOCRINE PANCREAS) is a compound acinar gland that secretes several digestive enzymes into the pancreatic ductal system that empties into the DUODENUM.Iron Overload: An excessive accumulation of iron in the body due to a greater than normal absorption of iron from the gastrointestinal tract or from parenteral injection. This may arise from idiopathic hemochromatosis, excessive iron intake, chronic alcoholism, certain types of refractory anemia, or transfusional hemosiderosis. (From Churchill's Illustrated Medical Dictionary, 1989)Iron Chelating Agents: Organic chemicals that form two or more coordination links with an iron ion. Once coordination has occurred, the complex formed is called a chelate. The iron-binding porphyrin group of hemoglobin is an example of a metal chelate found in biological systems.Transferrin: An iron-binding beta1-globulin that is synthesized in the LIVER and secreted into the blood. It plays a central role in the transport of IRON throughout the circulation. A variety of transferrin isoforms exist in humans, including some that are considered markers for specific disease states.Ferritins: Iron-containing proteins that are widely distributed in animals, plants, and microorganisms. Their major function is to store IRON in a nontoxic bioavailable form. Each ferritin molecule consists of ferric iron in a hollow protein shell (APOFERRITINS) made of 24 subunits of various sequences depending on the species and tissue types.Histocompatibility Antigens Class I: Membrane glycoproteins consisting of an alpha subunit and a BETA 2-MICROGLOBULIN beta subunit. In humans, highly polymorphic genes on CHROMOSOME 6 encode the alpha subunits of class I antigens and play an important role in determining the serological specificity of the surface antigen. Class I antigens are found on most nucleated cells and are generally detected by their reactivity with alloantisera. These antigens are recognized during GRAFT REJECTION and restrict cell-mediated lysis of virus-infected cells.Phlebotomy: The techniques used to draw blood from a vein for diagnostic purposes or for treatment of certain blood disorders such as erythrocytosis, hemochromatosis, polycythemia vera, and porphyria cutanea tarda.Hepcidins: Forms of hepcidin, a cationic amphipathic peptide synthesized in the liver as a prepropeptide which is first processed into prohepcidin and then into the biologically active hepcidin forms, including in human the 20-, 22-, and 25-amino acid residue peptide forms. Hepcidin acts as a homeostatic regulators of iron metabolism and also possesses antimicrobial activity.Receptors, Transferrin: Membrane glycoproteins found in high concentrations on iron-utilizing cells. They specifically bind iron-bearing transferrin, are endocytosed with its ligand and then returned to the cell surface where transferrin without its iron is released.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Iron, Dietary: Iron or iron compounds used in foods or as food. Dietary iron is important in oxygen transport and the synthesis of the iron-porphyrin proteins hemoglobin, myoglobin, cytochromes, and cytochrome oxidase. Insufficient amounts of dietary iron can lead to iron-deficiency anemia.Antimicrobial Cationic Peptides: Small cationic peptides that are an important component, in most species, of early innate and induced defenses against invading microbes. In animals they are found on mucosal surfaces, within phagocytic granules, and on the surface of the body. They are also found in insects and plants. Among others, this group includes the DEFENSINS, protegrins, tachyplesins, and thionins. They displace DIVALENT CATIONS from phosphate groups of MEMBRANE LIPIDS leading to disruption of the membrane.Pancreas Transplantation: The transference of a pancreas from one human or animal to another.HLA Antigens: Antigens determined by leukocyte loci found on chromosome 6, the major histocompatibility loci in humans. They are polypeptides or glycoproteins found on most nucleated cells and platelets, determine tissue types for transplantation, and are associated with certain diseases.Iron Metabolism Disorders: Disorders in the processing of iron in the body: its absorption, transport, storage, and utilization. (From Mosby's Medical, Nursing, & Allied Health Dictionary, 4th ed)Iron Radioisotopes: Unstable isotopes of iron that decay or disintegrate emitting radiation. Fe atoms with atomic weights 52, 53, 55, and 59-61 are radioactive iron isotopes.Chelation Therapy: Therapy of heavy metal poisoning using agents which sequester the metal from organs or tissues and bind it firmly within the ring structure of a new compound which can be eliminated from the body.Homozygote: An individual in which both alleles at a given locus are identical.Porphyria Cutanea Tarda: An autosomal dominant or acquired porphyria due to a deficiency of UROPORPHYRINOGEN DECARBOXYLASE in the LIVER. It is characterized by photosensitivity and cutaneous lesions with little or no neurologic symptoms. Type I is the acquired form and is strongly associated with liver diseases and hepatic toxicities caused by alcohol or estrogenic steroids. Type II is the familial form.Cation Transport Proteins: Membrane proteins whose primary function is to facilitate the transport of positively charged molecules (cations) across a biological membrane.Iron Compounds: Organic and inorganic compounds that contain iron as an integral part of the molecule.Hemosiderosis: Conditions in which there is a generalized increase in the iron stores of body tissues, particularly of liver and the MONONUCLEAR PHAGOCYTE SYSTEM, without demonstrable tissue damage. The name refers to the presence of stainable iron in the tissue in the form of hemosiderin.Pancreas, Exocrine: The major component (about 80%) of the PANCREAS composed of acinar functional units of tubular and spherical cells. The acinar cells synthesize and secrete several digestive enzymes such as TRYPSINOGEN; LIPASE; AMYLASE; and RIBONUCLEASE. Secretion from the exocrine pancreas drains into the pancreatic ductal system and empties into the DUODENUM.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Anemia, Iron-Deficiency: Anemia characterized by decreased or absent iron stores, low serum iron concentration, low transferrin saturation, and low hemoglobin concentration or hematocrit value. The erythrocytes are hypochromic and microcytic and the iron binding capacity is increased.Iron Isotopes: Stable iron atoms that have the same atomic number as the element iron, but differ in atomic weight. Fe-54, 57, and 58 are stable iron isotopes.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Deferoxamine: Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the mesylate form.Iron-Binding Proteins: Proteins that specifically bind to IRON.Penetrance: The percent frequency with which a dominant or homozygous recessive gene or gene combination manifests itself in the phenotype of the carriers. (From Glossary of Genetics, 5th ed)Ferric Compounds: Inorganic or organic compounds containing trivalent iron.Pancreatic Neoplasms: Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA).Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Duodenum: The shortest and widest portion of the SMALL INTESTINE adjacent to the PYLORUS of the STOMACH. It is named for having the length equal to about the width of 12 fingers.Heterozygote: An individual having different alleles at one or more loci regarding a specific character.Genetic Testing: Detection of a MUTATION; GENOTYPE; KARYOTYPE; or specific ALLELES associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing.Mythology: A body of stories, the origins of which may be unknown or forgotten, that serve to explain practices, beliefs, institutions or natural phenomena. Mythology includes legends and folk tales. It may refer to classical mythology or to a body of modern thought and modern life. (From Webster's 1st ed)Cytapheresis: Separation of one or more kinds of cells from whole blood with the return of other blood cell constituents to the patient or donor. This is accomplished with an instrument that uses centrifugation to separate the cells into different layers based on the differences in cell density (displacement) or drag coefficients in a current (elutriation). The procedure is commonly used in adoptive transfer to isolate NK cells, lymphocytes, or monocytes.Mutation, Missense: A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)Ferrous Compounds: Inorganic or organic compounds that contain divalent iron.Iron-Regulatory Proteins: Proteins that regulate cellular and organismal iron homeostasis. They play an important biological role by maintaining iron levels that are adequate for metabolic need, but below the toxicity threshold.Apoferritins: The protein components of ferritins. Apoferritins are shell-like structures containing nanocavities and ferroxidase activities. Apoferritin shells are composed of 24 subunits, heteropolymers in vertebrates and homopolymers in bacteria. In vertebrates, there are two types of subunits, light chain and heavy chain. The heavy chain contains the ferroxidase activity.Pancreatic Diseases: Pathological processes of the PANCREAS.GPI-Linked Proteins: A subclass of lipid-linked proteins that contain a GLYCOSYLPHOSPHATIDYLINOSITOL LINKAGE which holds them to the CELL MEMBRANE.Metal Metabolism, Inborn ErrorsPancreatic Ducts: Ducts that collect PANCREATIC JUICE from the PANCREAS and supply it to the DUODENUM.Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable.beta-Thalassemia: A disorder characterized by reduced synthesis of the beta chains of hemoglobin. There is retardation of hemoglobin A synthesis in the heterozygous form (thalassemia minor), which is asymptomatic, while in the homozygous form (thalassemia major, Cooley's anemia, Mediterranean anemia, erythroblastic anemia), which can result in severe complications and even death, hemoglobin A synthesis is absent.Chromosomes, Human, Pair 6: A specific pair GROUP C CHROMSOMES of the human chromosome classification.Intestinal Absorption: Uptake of substances through the lining of the INTESTINES.Siderosis: A form of pneumoconiosis resulting from inhalation of iron in the mining dust or welding fumes.Mononuclear Phagocyte System: Mononuclear cells with pronounced phagocytic ability that are distributed extensively in lymphoid and other organs. It includes MACROPHAGES and their precursors; PHAGOCYTES; KUPFFER CELLS; HISTIOCYTES; DENDRITIC CELLS; LANGERHANS CELLS; and MICROGLIA. The term mononuclear phagocyte system has replaced the former reticuloendothelial system, which also included less active phagocytic cells such as fibroblasts and endothelial cells. (From Illustrated Dictionary of Immunology, 2d ed.)Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules.HLA-A Antigens: Polymorphic class I human histocompatibility (HLA) surface antigens present on almost all nucleated cells. At least 20 antigens have been identified which are encoded by the A locus of multiple alleles on chromosome 6. They serve as targets for T-cell cytolytic responses and are involved with acceptance or rejection of tissue/organ grafts.Pancreas, Artificial: Devices for simulating the activity of the pancreas. They can be either electromechanical, consisting of a glucose sensor, computer, and insulin pump or bioartificial, consisting of isolated islets of Langerhans in an artificial membrane.Liver Diseases: Pathological processes of the LIVER.Bone Morphogenetic Protein 6: A bone morphogenetic protein that is a potent inducer of BONE formation. It plays additional roles in regulating CELL DIFFERENTIATION of non-osteoblastic cell types and epithelial-mesenchymal interactions.Bloodletting: Puncture of a vein to draw blood for therapeutic purposes. Bloodletting therapy has been used in Talmudic and Indian medicine since the medieval time, and was still practiced widely in the 18th and 19th centuries. Its modern counterpart is PHLEBOTOMY.beta 2-Microglobulin: An 11-kDa protein associated with the outer membrane of many cells including lymphocytes. It is the small subunit of the MHC class I molecule. Association with beta 2-microglobulin is generally required for the transport of class I heavy chains from the endoplasmic reticulum to the cell surface. Beta 2-microglobulin is present in small amounts in serum, csf, and urine of normal people, and to a much greater degree in the urine and plasma of patients with tubular proteinemia, renal failure, or kidney transplants.Anemia, Hypochromic: Anemia characterized by a decrease in the ratio of the weight of hemoglobin to the volume of the erythrocyte, i.e., the mean corpuscular hemoglobin concentration is less than normal. The individual cells contain less hemoglobin than they could have under optimal conditions. Hypochromic anemia may be caused by iron deficiency from a low iron intake, diminished iron absorption, or excessive iron loss. It can also be caused by infections or other diseases, therapeutic drugs, lead poisoning, and other conditions. (Stedman, 25th ed; from Miale, Laboratory Medicine: Hematology, 6th ed, p393)Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.Pancreatitis: INFLAMMATION of the PANCREAS. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of CHRONIC PANCREATITIS (International Symposium on Acute Pancreatitis, Atlanta, 1992). The two most common forms of acute pancreatitis are ALCOHOLIC PANCREATITIS and gallstone pancreatitis.Iron Regulatory Protein 1: A multifunctional iron-sulfur protein that is both an iron regulatory protein and cytoplasmic form of aconitate hydratase. It binds to iron regulatory elements found on mRNAs involved in iron metabolism and regulates their translation. Its RNA binding ability and its aconitate hydrolase activity are dependent upon availability of IRON.Anemia, Dyserythropoietic, Congenital: A familial disorder characterized by ANEMIA with multinuclear ERYTHROBLASTS, karyorrhexis, asynchrony of nuclear and cytoplasmic maturation, and various nuclear abnormalities of bone marrow erythrocyte precursors (ERYTHROID PRECURSOR CELLS). Type II is the most common of the 3 types; it is often referred to as HEMPAS, based on the Hereditary Erythroblast Multinuclearity with Positive Acidified Serum test.Islets of Langerhans: Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN.Hemoglobins: The oxygen-carrying proteins of ERYTHROCYTES. They are found in all vertebrates and some invertebrates. The number of globin subunits in the hemoglobin quaternary structure differs between species. Structures range from monomeric to a variety of multimeric arrangements.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Pancreatectomy: Surgical removal of the pancreas. (Dorland, 28th ed)Anemia, Sideroblastic: Anemia characterized by the presence of erythroblasts containing excessive deposits of iron in the marrow.Uroporphyrinogen Decarboxylase: An enzyme that catalyzes the decarboxylation of UROPORPHYRINOGEN III to coproporphyrinogen III by the conversion of four acetate groups to four methyl groups. It is the fifth enzyme in the 8-enzyme biosynthetic pathway of HEME. Several forms of cutaneous PORPHYRIAS are results of this enzyme deficiency as in PORPHYRIA CUTANEA TARDA; and HEPATOERYTHROPOIETIC PORPHYRIA.Amylases: A group of amylolytic enzymes that cleave starch, glycogen, and related alpha-1,4-glucans. (Stedman, 25th ed) EC 3.2.1.-.Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.Blood Transfusion: The introduction of whole blood or blood component directly into the blood stream. (Dorland, 27th ed)Iron Regulatory Protein 2: A multifunctional iron-sulfur protein that is both an iron regulatory protein and cytoplasmic form of aconitate hydratase. It binds to iron regulatory elements found on mRNAs involved in iron metabolism and regulates their translation. Its rate of degradation is increased in the presence of IRON.
  • Your doctor will diagnose hemochromatosis based on your medical and family histories, a physical exam, and the results from tests and procedures. (medlineplus.gov)
  • I believe that his suicide was caused by his doctors' complete failure to diagnose hemochromatosis, a hereditary disease that was so well known and so easy to treat that he could have had no suffering at all (Front Neurol Neurosci, 2010;27:174-206). (drmirkin.com)
  • Pigment changes: Bronze or grey coloration of the skin is caused primarily by increased melanin deposition, with iron deposition playing a lesser role. (wikipedia.org)
  • Postmortem examinations have revealed the parenchymal cell deposition of iron in the pancreas to be from 50 to 100 times normal. (mdedge.com)
  • We have disrupted the murine Hjv gene and shown that Hjv -/- mice have markedly increased iron deposition in liver, pancreas, and heart but decreased iron levels in tissue macrophages. (jci.org)
  • See 'Iron deposition' below and 'Cartilage defect' below and 'Immunologic defects' below. (uptodate.com)
  • A) Coronal gradient echo image at the level of the heart shows hypointense signal in the myocardium indicating iron deposition and (B) axial gradient echo MRI scan through the upper abdomen showing hypointense signal in the liver, spleen, and the pancreas. (bmj.com)
  • 2) Reticuloendothelial cell iron deposition (see box 2)-this is seen most commonly in patients who have received multiple transfusions and also in patients with rhabdomyolysis. (bmj.com)
  • 2 Parenchymal cell iron deposition leads to cellular damage and organ dysfunction unless treated. (bmj.com)
  • However, pancreatic iron deposition in transfusional iron overload may result from massive transfusion beyond the iron storage capacity of the reticuloendothelial cell system (10 g), which is the amount of iron in 40 units of blood. (bmj.com)
  • 3 Reticuloendothelial iron deposition does not produce any significant organ dysfunction. (bmj.com)
  • The endpoints of this proof-of-concept study include change in TSAT and serum iron levels, reductions in phlebotomy requirements, and an assessment of participant-reported outcomes (SF-36 survey). (prnewswire.com)
  • HOW: Haemochromatosis is diagnosed by the typical physical and radiographic findings supported by elevated serum iron concentrations and high transferrin saturations. (dermis.net)
  • A wise physician will order iron studies that include serum iron and total iron binding capacity (TIBC) blood tests. (diabetesnet.com)