Thalassemias

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What is thalassemia?

Normal hemoglobin (Hb) is a heterodimer of two globins produced as a result of expression of genes from the alpha (α)-globin gene cluster on chromosome 16 and two globins produced as a result of expression of genes from the beta (β)-globin gene cluster on chromosome 11. Thalassemia refers to a group of congenital disorders of globin synthesis in which there is decreased or absent production of one of the two subunits of Hb. Thus it is a quantitative hemoglobinopathy. The most common thalassemias are α and β, with a reduction or absence of production of the respective globins. Other forms of thalassemia include gamma (γ)-β and delta (δ)-γ-β thalassemia, which are less common. The severity of thalassemia depends in large part on the degree of imbalance between α- and β-globin chains.

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Where are the thalassemia syndromes more commonly found?

The term thalassemia comes from the Greek words thalassa (“sea”) and haema (“blood”), referencing the fact that these syndromes were first described in individuals living around the Mediterranean Sea. The β thalassemias are more common around the Mediterranean, including Europe and North Africa, and the Middle East, the Indian Subcontinent, and Southeast Asia, whereas α thalassemia occurs in high frequencies in the Far East and China.

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How are α thalassemia and β thalassemia different?

α thalassemia refers to decreased or absent α-globin synthesis, caused by deletions or mutations of one, two, three, or all four α-globin genes (two on each chromosome).

β thalassemia refers to decreased or absent β-chain synthesis, resulting from any of over almost 300 gene defects, including point mutations and deletions in one or both of the β-globin genes. Point mutations have variable effects on gene regulation and expression. Completely absent expression of the β-globin gene is referred to as a β-zero (β ⁰ ) allele, whereas reduced or partial expression is classified as a β-plus (β ⁺ ) allele.

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What is thalassemia trait?

Thalassemia trait results from decreased, but not absent, production of either the α- or β-globin chain. In α-thalassemia trait, there is usually deletion of two of the four α-globin genes. In β-thalassemia trait, one of the two β-globin genes is abnormal. In either case, the decrease in globin production results in mild anemia, and affected individuals are generally asymptomatic without other complications of thalassemia.

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What are the characteristic complete blood cell (CBC) findings in thalassemia trait?

With both α- and β-thalassemia trait, there is usually a mild microcytic anemia with an increased red blood cell (RBC) count. Microcytic anemia is most commonly seen with iron deficiency. Thalassemia trait may be distinguished from iron deficiency by the increased RBC count, normal red cell distribution width values (RDW), and the Mentzer index. The Mentzer index is the mean corpuscular volume (MCV) divided by the RBC count (in millions). A Mentzer index of less than 12 suggests thalassemia trait, whereas an index of greater than 13 suggests iron deficiency, with an index between 12 and 13 requiring some additional testing.

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