Thalassemia is an inherited blood disorder which causes abnormal production of hemoglobin. The symptoms of the disease vary from individual to individual; most patients are characterized by mild to severe anemia. The other symptoms of Thalassemia include an enlarged spleen, yellowish skin, and dark urine.
One of the reasons for the prevalence of thalassemia in the tropical and subtropical region is because of malaria. Thalassemia has found to be prevalent in Asian countries such as the Maldives, India and Thailand, Europe, southern parts of Italy and Greece and Northern part of the African continent.
Is Thalassemia A Rare Disease?
Thalassemia affects every 5th child in 10,000 live births throughout the world. There is no gender bias for the disease, both male and females can inherit the gene mutations. Thalassemia gene mutations follow an autosomal pattern of inheritance. Approximately 5% population across the globe has an alpha or beta globin gene mutation. Not all the people carrying the gene are symptomatic only 1.7% of the population shows signs of gene mutation i.e. thalassemia trait.
One of the rare forms of thalassemia is delta and globin subunit thalassemia. These forms of thalassemia are not clinically significant.
Alpha Thalassemia. The alpha globin chain part is defective giving faulty hemoglobin. The two types of alpha thalassemia which require attention are Hb Bart syndrome; this is the most severe form and HbH disease, the milder form.
Beta Thalassemia. The beta globin chain part is defective giving faulty hemoglobin. Thalassemia major (also called Cooley’s anemia) is the most severe form of the disease and Thalassemia intermedia is a milder form of disease-causing mild anemia.
The beta globin chains subunits get deleted resulting in beta deletion form of thalassemia, this occurs because of the unequal crossing of the links between alpha and beta chains resulting in the formation of fusion alpha and beta-globin gene, the Lepore gene.
Large type deletions in the beta globin chain subunits can result in alpha-beta thalassemia, gamma-alpha-beta thalassemia and the hereditary persistence of fetal hemoglobin (HPFH) syndromes.
Patients suffering from severe beta-thalassemia mandatorily require blood transfusions and there will be an increase in iron overload. Excess iron is to be removed from the body, hence medical interventions required to remove excess iron are given such as deferasirox (Exjade, Jadenu). These medications remove iron from the body.
Structure of Hemoglobin
Hemoglobin is composed of four globin chains. Fetal hemoglobin (Hb F) has two α and two gamma chains whereas adult hemoglobin (Hb A) has two α and two β chains (α2β2). The genes which are present in the alpha and beta globin gene clusters control the production of globin chain. The four globin chain subunits are connected to a heme group. Heme group contains the iron in it which is responsible for carrying oxygen.
Spontaneous mutation in hemoglobin gene variants happens in low percentage but in sizeable populations, it is often referred to as structural variation. This mutation results in abnormal production of hemoglobin due to change in the amino acid sequence. Mutations change the amino acid sequence resulting in abnormal production of hemoglobin. Abnormally produced hemoglobin causes mild to severe anemia. Any spontaneous variation in the gene clusters of alpha or beta globin chain results in alpha or beta thalassemia. In Thalassemia, there will be decreased production of globin chains or stop production of globin chain.
Thalassemia is an inherited qualitative blood disorder characterized by abnormal production of hemoglobin. The faulty alpha and beta globin chains result from alpha or beta thalassemia respectively. Thalassemia can be seen in 4.4 of every 10,000 live births throughout the world. 1.7% of the global population is affected by thalassemia. The disease is not gender bias and can be seen in both males and females. The occurrence of individual forms of thalassemia is rare and detailed studies are required to determine the occurrence of individual form of thalassemia.