|  | Conditions Treatments | Blood Disorders

What Are the Causes of Thalassemia?

Thalassemias are a group of autosomal recessive hereditary blood diseases caused by disrupted hemoglobin (Hb) synthesis. Thalassemia can result in hemolytic anemia, with red blood cell (RBC) destruction. Severity ranges from asymptomatic forms to life-threatening disease. Because the disease is hereditary, it occurs in clusters and is most prevalent in those with African, Mediterranean or Southeast Asian ancestry.

  1. What is Hemoglobin?

    • Hb is an iron-containing metalloprotein. In normal adult humans, the metalloprotein is composed of four globular subunits of Hb (two alpha subunits and two beta subunits), each carrying a heme group. In turn, each heme group carries one iron atom that binds one oxygen molecule. In total, one adult human Hb protein typically carries four oxygen molecules.

    Role of Hemoglobin

    • Hb transports oxygen from the lungs to body tissues, releases oxygen for cell use and then returns the carbon dioxide produced in the tissues to the lungs, to be exhaled. Alterations in the structure and function of Hb can destroy RBCs, causing anemia.

    Genetic Mutations

    • Four genes (two from each parent) are vital for normal levels of alpha-globulin, and two genes (one from each parent) are vital for normal levels of beta-globulin. Any mutation in a globular subunit gene can alter the protein's structure and function. The two categories of thalassemia are alpha-thalassemia and beta-thalassemia, described by the globulin chain that is underproduced because of the mutation. Normally, when the metalloprotein folds into its unique shape, each alpha subunit pairs with a beta subunit. In thalassemia, the excess of normally produced component accumulates and destroys the red blood cell. The severity of the disease depends on the number of genes that are mutated.

    Alpha-Thalassemia

    • The mildest form of alpha-thalassemia, with one mutated alpha-globulin gene, is asymptomatic, but the individual can pass the mutated gene to offspring. A milder form, with two mutated genes, can be asymptomatic or cause mild anemia. At the other end of the spectrum, three mutated alpha-globulin genes result in severe anemia, called hemoglobin H disease. Four mutated alpha-globulin genes cause alpha-thalassemia major. Also called hydrops fetalis, this usually causes fetal death or death shortly after birth.

    Beta-Thalassemia

    • When one beta-globulin gene is mutated, beta-thalassemia is usually asymptomatic. Two mutated beta-globulin genes can cause either thalassemia intermedia or thalassemia major, requiring blood transfusions and iron-chelation therapy. Thalassemia major can be life-threatening.

Blood Disorders - Related Articles