Thalassemia

Thalassemia (British English: thalassaemia), also called Mediterranean anemia, is a form of inherited autosomal recessive blood disorder characterized by abnormal formation of hemoglobin. The abnormal hemoglobin formed results in improper oxygen transport and destruction of red blood cells. Thalassemia is caused by variant or missing genes that affect how the body makes hemoglobin, the protein in red blood cells that carries oxygen. People with thalassemia make less hemoglobin and have fewer circulating red blood cells than normal, which results in mild or severe microcytic anemia.

Thalassemia can cause complications, including iron overload, bone deformities, and cardiovascular illness. However, this same inherited disease of red blood cells may confer a degree of protection against malaria (specifically, malaria caused by the protozoan parasite Plasmodium falciparum), which is or was prevalent in the regions where the trait is common. This selective survival advantage of carriers (known as heterozygous advantage) may be responsible for perpetuating the mutation in populations. In that respect, the various thalassemias resemble another genetic disorder affecting hemoglobin, sickle-cell disease.

Alpha-thalassemia

Alpha-thalassemia (α-thalassemia, α-thalassaemia) is a form of thalassemia involving the genes HBA1 and HBA2. Alpha-thalassemia is due to impaired production of alpha chains from 1,2,3, or all 4 of the alpha globin genes, leading to a relative excess of beta globin chains. The degree of impairment is based on which clinical phenotype is present (how many genes are affected).

Epidemiology

The worldwide distribution of inherited alpha-thalassemia corresponds to areas of malaria exposure, suggesting a protective role for alpha-thalassemia against the more severe manifestations of malaria. Thus, alpha-thalassemia is common in sub-Saharan Africa, the Mediterranean Basin, the Middle East, South Asia, and Southeast Asia, and different genetic subtypes have variable frequencies in each of these areas. The epidemiology of alpha-thalassemia in the US reflects this global distribution pattern. The most common form of alpha(+) thalassemia seen in the US is due to the -alpha(3.7) deletion, a single alpha-globin gene deletion, and is present in approximately 30% of African Americans. However, even in the homozygous state this disorder will result only in a mild microcytic anemia. The more serious clinical disorders of Hb H and Hb Bart hydrops fetalis syndrome, although found throughout the US today, are more common in the Western US and have dramatically increased in prevalence in the past 2 decades due to increased Asian immigration.

Beta thalassemia

Beta thalassemias (β thalassemias) are a group of inherited blood disorders. They are caused by reduced or absent synthesis of the beta chains of hemoglobin that result in variable outcomes ranging from severe anemia to clinically asymptomatic individuals. Global annual incidence is estimated at 1 in 100,000. Beta thalassemia (β thalassemia) is a form of thalassemia caused by mutations in the HBB gene on chromosome 11, inherited in an autosomal recessive fashion. The severity of the disease depends on the nature of the mutation.

HBB blockage over time leads to decreased Beta-chain synthesis. The body’s inability to construct new Beta-chains leads to the underproduction of HBA. Reductions in HBA available overall to fill the red blood cells in turn leads to microcytic anemia. Microcytic anemia ultimately develops in respect to inadequate HBB for sufficient red blood cell functioning. Due to this factor, the patient must undergo a blood transfusion for survival to make up for the blockage in the Beta-chains. Repeated blood transfusions lead to build-up of iron overload ultimately resulting in iron toxicity. This iron toxicity produces myocardial siderosis and heart failure leading to the patient’s death.