Beta thalassemia

Beta-thalassemia (β-thalassemia) is an inherited blood disorder, a form of thalassemia resulting in variable outcomes ranging from clinically asymptomatic to severe anemia individuals. It is caused by reduced or absent synthesis of the beta chains of hemoglobin, the molecule that carries oxygen in the blood.^[7] Symptoms depend on the extent to which hemoglobin is deficient, and include anemia, pallor, tiredness, enlargement of the spleen, jaundice, and gallstones. In severe cases death ensues.^[8]

Beta thalassemia occurs due to a mutation of the HBB gene leading to deficient production of the hemoglobin subunit beta-globin; the severity of the disease depends on the nature of the mutation, and whether or not the mutation is homozygous.^[9][10] The body's inability to construct beta-globin leads to reduced or zero production of adult hemoglobin thus causing anemia.^[11] The other component of hemoglobin, alpha-globin, accumulates in excess leading to ineffective production of red blood cells, increased hemolysis, and iron overload.^[12] Diagnosis is by checking the medical history of near relatives, microscopic examination of blood smear, ferritin test, hemoglobin electrophoresis, and DNA sequencing.^[13]

As an inherited condition, beta thalassemia cannot be prevented although genetic counselling of potential parents prior to conception can propose the use of donor sperm or eggs.^[14] Patients may require repeated blood transfusions throughout life to maintain sufficient hemoglobin levels; this in turn may lead to severe problems associated with iron overload.^[1] Medication includes folate supplementation, iron chelation, bisphosphonates, and removal of the spleen.^[15] Beta thalassemia can also be treated by bone marrow transplant from a well matched donor,^[16] or by gene therapy.^[17]

Thalassemias were first identified in severely sick children in 1925,^[18] with identification of alpha and beta subtypes in 1965.^[19] Beta-thalassemia tends to be most common in populations originating from the Mediterranean, the Middle East, Central and Southeast Asia, the Indian subcontinent, and parts of Africa. This coincides with the historic distribution of Plasmodium falciparum malaria, and it is likely that a hereditary carrier of a gene for beta-thalassemia has some protection from severe malaria. However, because of population migration, β-thalassemia can be found around the world.^[13] In 2005, it was estimated that 1.5% of the world's population are carriers and 60,000 affected infants are born with the thalassemia major annually.^[20]