The term haemochromatosis was initially used to refer to what is now more specifically called haemochromatosis type 1 (or HFE-related hereditary haemochromatosis). Currently, haemochromatosis (without further specification) is mostly defined as<unk>  with a hereditary or primary cause, or originating from a metabolic disorder. However, the term is currently also used more broadly to refer to any form of<unk> , thus requiring specification of the cause, for example, hereditary haemochromatosis. Hereditary haemochromatosis is an autosomal recessive disorder with estimated prevalence in the population of 1 in 200 among patients with European ancestry, with lower incidence in other ethnic groups. The gene responsible for hereditary haemochromatosis (known as HFE gene) is located on chromosome 6; the majority of hereditary haemochromatosis patients have mutations in this HFE gene. Hereditary haemochromatosis is characterized by an accelerated rate of intestinal iron absorption and progressive iron deposition in various tissues. This typically begins to be expressed in the third to fifth decades of life, but may occur in children. The most common presentation is hepatic cirrhosis in combination with hypopituitarism, cardiomyopathy, diabetes, arthritis, or hyperpigmentation. Because of the severe sequelae of this disorder if left untreated, and recognizing that treatment is relatively simple, early diagnosis before symptoms or signs appear is important. In general, the term haemosiderosis is used to indicate the pathological effect of iron accumulation in any given organ, which mainly occurs in the form of the iron-storage complex haemosiderin. Sometimes, the simpler term siderosis is used instead. Other definitions distinguishing haemochromatosis or haemosiderosis that are occasionally used include: * Haemosiderosis is haemochromatosis caused by excessive blood transfusions, that is, haemosiderosis is a form of secondary haemochromatosis. * Haemosiderosis is haemosiderin deposition within cells, while haemochromatosis is haemosiderin within cells and interstitium. * Haemosiderosis is<unk>  that does not cause tissue damage, while haemochromatosis does. * Haemosiderosis is arbitrarily differentiated from haemochromatosis by the reversible nature of the iron accumulation in the reticuloendothelial system. The causes of haemochromatosis broken down into two subcategories: primary cases (hereditary or genetically determined) and less frequent secondary cases (acquired during life). People of 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. This has been recognised in several laymans' alternative names such as Celtic curse, Irish illness, British gene, and Scottish sickness. 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 haemochromatosis", "non-HFE related hereditary haemochromatosis", or "non-HFE haemochromatosis". Description OMIM Mutation Haemochromatosis type 1: "classical" haemochromatosis HFE Haemochromatosis type 2A: juvenile haemochromatosis Haemojuvelin (HJV, also known as RGMc and HFE2) Haemochromatosis type 2B: juvenile haemochromatosis hepcidin antimicrobial peptide (HAMP) or HFE2B Haemochromatosis type 3 transferrin receptor-2 (TFR2 or HFE3) Haemochromatosis type 4 / African<unk>  ferroportin (SLC11A3/SLC40A1) Neonatal haemochromatosis (unknown) Acaeruloplasminaemia (very rare) caeruloplasmin Congenital atransferrinaemia (very rare) transferrin GRACILE syndrome (very rare) BCS1L Most types of hereditary haemochromatosis have autosomal recessive inheritance, while type 4 has autosomal dominant inheritance. Secondary haemochromatosis * Severe chronic haemolysis of any cause, including intravascular haemolysis and ineffective erythropoiesis (haemolysis within the bone marrow) * Multiple frequent blood transfusions (either whole blood or just red blood cells), which are usually needed either by individuals with hereditary anaemias (such as beta-thalassaemia major, sickle cell anaemia, and Diamond–Blackfan anaemia) or by older patients with severe acquired anaemias such as in myelodysplastic syndromes. * Excess parenteral (non-ingested) iron supplements, such as what can acutely happen in iron poisoning * Excess dietary iron * Some disorders do not normally cause haemochromatosis on their own, but may do so in the presence of other predisposing factors. These include cirrhosis (especially related to alcohol use disorder), steatohepatitis of any cause, porphyria cutanea tarda, prolonged haemodialysis, and post-portacaval shunting
Iron overload
Zinc toxicity
Lead poisoning
Iron poisoning
Fluoride toxicity
Copper toxicity
Metal toxicity
Ochronosis