Thalassemia

Thalassemias are a heterogeneous group of genetic disorders characterized by reduced synthesis of alpha or beta chains of hemoglobin (Hb). Hemoglobin serves as the oxygen-carrying component of red blood cells. It consists of two proteins: alpha and beta. If the body does not produce sufficient amounts of either of these two proteins, red blood cells do not form correctly and cannot carry sufficient oxygen, resulting in anemia that begins in early childhood and persists throughout life. Thalassemia is an inherited disease, meaning that at least one parent must be a carrier. It is caused by either a genetic mutation or a deletion of certain key gene fragments. is caused by alpha-globin gene deletion, which results in reduced or absent production of alpha-globin chains. The alpha globin gene has 4 alleles, and disease severity ranges from mild to severe depending on the number of deletions of the alleles. Four-allele deletion is the most severe form, in which no alpha globins are produced, and the excess gamma chains (present during the fetal period) form tetramers. It is incompatible with life and results in hydrops fetalis. One allele deletion is the mildest form and is mostly clinically silent. results from point mutations in the beta-globin gene. It is divided into three categories based on the zygosity of the beta-gene mutation. A heterozygous mutation (beta-plus thalassemia) results in beta-thalassemia minor, in which beta chains are underproduced. It is mild and usually asymptomatic. Beta thalassemia major is caused by a homozygous mutation (beta-zero thalassemia) of the beta-globin gene, resulting in the total absence of beta chains. It manifests clinically as jaundice, growth retardation, hepatosplenomegaly, endocrine abnormalities, and severe anemia requiring life-long blood transfusions. The condition between these two types is called beta-thalassemia intermedia, characterized by mild to moderate clinical symptoms. : Mild signs and symptoms. The condition is called thalassemia minor.  Signs and symptoms will be moderate to severe. This condition is called thalassemia major, or Cooley anemia. Babies born with two mutated beta hemoglobin genes are usually healthy at birth, but the disease starts to manifest after 6 months of life when fetal hemoglobin (Hb-gamma) disappears and is replaced by adult Hb. The excess unpaired alpha-globin chains in beta-thalassemia aggregate and form precipitates that damage red cell membranes and result in intravascular hemolysis. This premature death of erythroid precursor cells leads to ineffective erythropoiesis and, subsequently, to extramedullary hematopoiesis.  Beta-thalassemia patients with coinheritance of alpha-thalassemia have a milder clinical course due to a less severe alpha-beta chain imbalance. The presence of sickle cell trait with beta-thalassemia is a common hemoglobinopathy and can lead to manifestations of sickle cell disease. Unlike sickle cell trait, in which major Hb is HbA, in the co-existence state, the major Hb is HbS, which constitutes more than 60% of Hb, depending on the nature of the disease (beta-zero or beta-plus0) Hemoglobin (HbE) is also a common Hb variant found in the Southeast Asian population. It is associated with a beta-thalassemia phenotype, as individuals with thalassemia in this region are commonly found to have HbE.   Two new terms used more frequently in clinical settings are transfusion-requiring and non-transfusion-requiring thalassemias; all basic classifications fall into these two types, depending on the need for frequent blood transfusions.