Thalassemia (American English) (or Thalassaemia in British English) is an inherited disease of the red blood cells, classified as a hemoglobinopathy. The genetic defect results in synthesis of an abnormal hemoglobin molecule. The blood cells are vulnerable to mechanical injury and die easily. To survive, many people with thalassaemia need blood transfusions at regular intervals. American English or U.S. English is the diverse form of the English language used mostly in the United States of America. ... Diagram showing the geographical locations of selected languages and dialects of the British Isles. ... To inherit something is to get it from ones ancestors. ... Blood diseases affect the production of blood and its components, such as blood cells, hemoglobin, blood proteins, the mechanism of coagulation, etc. ... Human red blood cells Red blood cells are the most common type of blood cell and are the vertebrate bodys principal means of delivering oxygen to body tissues via the blood. ... Hemoglobinopathy is a kind of genetic defect that results in abnormal structure of one of the globin chains of the hemoglobin molecule. ... 3-dimensional structure of hemoglobin Hemoglobin or haemoglobin is the iron-containing oxygen-transport metalloprotein in the red cells of the blood in mammals and other animals. ... Blood transfusion is the taking of blood or blood-based products from one individual and inserting them into the circulatory system of another. ...

Being a carrier of the disease confers a degree of protection against malaria, and is quite common among people from Italian or Greek origin, since malaria was widespread in those countries at a time. In that respect it resembles another genetic disease, sickle-cell anemia. Red blood cell infected with Malaria (Italian: bad air; formerly called ague or marsh fever in English) is an infectious disease which causes about 500 million infections and 2 million deaths annually, mainly in the tropics and sub-Saharan Africa. ... The Italian Republic or Italy ( Italian: Repubblica Italiana or Italia) is a country in southern Europe. ... Red blood cell infected with Malaria (Italian: bad air; formerly called ague or marsh fever in English) is an infectious disease which causes about 500 million infections and 2 million deaths annually, mainly in the tropics and sub-Saharan Africa. ... A genetic disorder, or genetic disease is a disease caused, at least in part, by the genes of the person with the disease. ... Sickle-shaped red blood cells Sickle cell anemia (American English), sickle cell anaemia (British English) or sickle cell disease is a genetic disease in which red blood cells may change shape under certain circumstances. ...

The thalassemias are classified according to which chain of the globin molecule is affected: in α thalassemia, the production of α globin is deficient, while in β thalassemia the production of β globin is defective. Thalassemia produces a deficiency of α or β globin, unlike sickle-cell anemia which produces a specific mutant form of β globin. Sickle-shaped red blood cells Sickle cell anemia (American English), sickle cell anaemia (British English) or sickle cell disease is a genetic disease in which red blood cells may change shape under certain circumstances. ...

Both α and β thalassemia are inherited in an autosomal recessive fashion. Both parents must be carriers in order for a child to be affected. If both parents carry a hemoglobinopathy trait, there is a 25% chance with each pregnancy for an affected child. Genetic counseling and genetic testing is recommended for families that carry a thalassemia trait. Genetic counseling generally refers to prenatal counseling done when a genetic condition is suspected in a pregnancy. ... Genetic testing allows the genetic diagnosis of vulnerabilities to inherited diseases, and can also be used to determine a persons ancestry. ...

Alpha thalassemias

The alpha thalassemias involve the genes HBA1 (OMIM 141800  (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141800)) and HBA2 (OMIM 141850  (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141850)). α thalassemias result in excess β chain production in adults and excess γ chains in newborns. The excess β chains form unstable tetramers that have abnormal oxygen dissociation curves. 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 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. ...

There are four genetic loci for α globin. The more of these loci that are deleted or affected by mutation, the more severe will be the manifestations of the disease.

If all four loci are affected, the fetus cannot live once outside the uterus: most such infants are dead at birth with hydrops fetalis, and those who are born alive die shortly after birth. They are edematous and have little circulating hemoglobin, and the hemoglobin that is present is all tetrameric γ chains (hemoglobin Barts). Fetus at eight weeks A fetus (alternatively foetus or fœtus) is an embryo in later stages of development, from the third month of pregnancy until birth in humans. ... Hydrops fetalis is blood condition in the fetus characterized by an edema in the fetal subcutaneous tissue. ...

If three loci are affected, Hemoglobin H disease results. Two unstable hemoglobins are present in the blood, both hemoglobin Barts and hemoglobin H (tetrameric β chains). There is a microcytic hypochromic anemia with target cells and Heinz bodies on the peripheral blood smear. The disease may first be noticed in childhood or in early adult life, when the anemia and splenomegalyare noted. Anemia ( American English) or anaemia ( Commonwealth English), which literally means without blood, is a lack of red blood cells and/or hemoglobin. ... Target cells are the sites where hormones act. ... A microscopic view of an abnormal blood film. ... Splenomegaly is an enlargement of the spleen. ...

If two of the four α loci are affected, α-thalassemia trait results. Two α loci permit nearly normal erythropoiesis, though there is a mild microcytic hypochromic anemia. There is a high prevalence (about 30%) of deletion of one of the two α loci on chromosomes of people of recent African origin, and so the inheritance of two such chromosomes is not uncommon. The disease in this form can be mistaken for iron deficiency anemia and treated inappropriately with iron. Erythropoiesis is the process by which red blood cells (erythrocytes) are produced. ... Iron deficiency anemia is the most common type of anemia, and the most common cause of microcytic anemia. ...

If one of the four α loci is affected, there is minimal effect. Three α-globin loci are enough to permit normal hemoglobin production, and there is no anemia or hypochromia in these people. They have been called α thalassemia carriers. Anemia ( American English) or anaemia ( Commonwealth English), which literally means without blood, is a lack of red blood cells and/or hemoglobin. ...

Beta thalassemias

Beta thalassemia is due to mutations in the HBB gene HBB (OMIM 141900  (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141900)). In β thalassemia, excess α chains are produced, but these do not form tetramers: rather, they bind to the red blood cell membranes, producing membrane damage. The severity of the damage depends on the nature of the mutation. Some mutations (β^o) prevent any formation of β chains; others (β⁺) allow some β chain formation to occur. 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. ... Human red blood cells Red blood cells are the most common type of blood cell and are the vertebrate bodys principal means of delivering oxygen to body tissues via the blood. ...

There are two β globin genes. If both have thalassemia mutations, a severe anemia called β thalassemia major or Cooley's anemia results. Untreated, this results in death before age twenty: treatment consists of periodic blood transfusion; splenectomy if splenomegaly is present, and treatment of transfusion-caused iron overload. Cure is possible by bone marrow transplantation. Blood transfusion is the taking of blood or blood-based products from one individual and inserting them into the circulatory system of another. ... Bone marrow transplantation is a medical procedure that involves stem cell transplantation. ...

If only one β globin gene bears a mutation, β thalassemia minor results. This is a mild anemia with microcytosis. Symptoms include weakness and fatigue - in most cases β thalassemia minor may be asymptomatic and many people may be unaware they have this disorder. Detection usually involves counting the mean corpuscular volume (size of red blood cells) and noticing a slightly decreased mean volume then is normal. Fatigue is a feeling of excessive tiredness or lethargy, with a desire to rest, perhaps to sleep. ...

In combination with other hemoglobinopathies

Thalassemia can co-exist with other hemoglobinopathies. The most common of these are:

• hemoglobin E/thalassemia: common in Cambodia and Thailand, clinically similar to β thalassemia major
• hemoglobin S/thalassemia, common in African and Mediterranean populations; clinically similar to sickle cell anemia, with the additional feature of splenomegaly
• hemoglobin C/thalassemia: common in Mediterranean and African populations, hemoglobin C/β^o thalassemia causes a moderately severe hemolytic anemia with splenomegaly; hemoglobin C/β⁺ thalassemia produces a milder disease.

Complications of tranfusions

Repeated transfusions leads to the accumulation of iron in the heart and liver. If untreated it invariably leads to death (by heart failure). Complications with high iron levels can be avoided through the use of chelators such as deferoxamine (also called desferrioxamine) and deferiprone. Of the two, deferoxamine is preferred; it is associated with fewer side-effects.[1] A side-effect is any effect other than an intended primary effect. ...

Thalassemia in Cyprus

A screening policy exists on both sides of the island of Cyprus to reduce the incidence of thalassemia, which since the program's implementation in the 1970s (which also includes pre-natal screening and abortion) has reduced the number of children born with the hereditary blood disease from 1 out of every 158 births to almost zero. Cyprus (in Greek Kypros Κύπρος and in Turkish Kıbrıs) is an island in the eastern Mediterranean Sea, 113 kilometres (70 miles) south of Turkey and around 120 km west of the Syrian coast. ...

References

1. Maggio A, D'Amico G, et al. Deferiprone versus deferoxamine in patients with thalassemia major: a randomized clinical trial. Blood Cells Mol Dis. 2002 Mar-Apr;28(2):196-208. PMID 12064916.