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Thalassaemia is an inherited disease of the erythrocytes (the red blood cells), classified as a hemoglobinopathy: the genetic disorder 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.

This disease tends to occur in areas with a past history of malaria, since it confers a degree of protection against that disease. In that respect it resembles another genetic disease, sickle-cell anemia.

The thalasassemias 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.

Alpha thalassemias

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.

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).

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 childhoood or in early adult life, when the anemia and splenomegaly is noted.

If two of the four α loci are affected, α-thalassemia trait results. Two α loci permit nearly normal erythropoiesis, though there is a middle microcytic hypochomic 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 chormosomes is not uncommon. The disease in this form can be mistaken for iron deficiency anemia and treated inappropriately with iron.

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.

Beta thalassemias

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 (βo) prevent any formation of β chains; others (β+) allow some β chain formation to occur.

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 transfusion; splenectomy if splenomegaly is present, and treatment of transfusion-caused iron overload. Cure is possible by bone marrow transplantation.

If only one β globin gene bears a mutation, β thalassemia minor results. This is a mild anemia with microcytosis. Symptoms are weakness and fatigue.

Thalassemia in combination with other hemoglobinopathies

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