Introduction to thalassemia

The term “thalassemia” is derived from the Greek words “Thalassa” (sea) and “Haema” (blood) and refers to disorders associated with defective synthesis of α- or β-globin subunits of hemoglobin (Hb) A (α2; β2), inherited as pathologic alleles of one or more of the globin genes located on chromosomes 11 (β) and 16 (α). More than 200 deletions or point mutations that impair transcription, processing, or translation of α- or β-globin mRNA have been identified. The clinical manifestations are diverse, ranging from absence of symptoms to profound fatal anemias in utero, or, if untreated, in early childhood.1


The thalassemia syndrome is classified according to which of the globin chains, α or β, is affected. These 2 major groups, α- and β-thalassemia, are subclassified according to absent (α° and β°) or reduced (α+ or β+) globin chain synthesis. In addition, where γ-chains together with α-chains compose fetal hemoglobin (HbF) in the fetus and δ chains in combination with α-chains compose hemoglobin A2 in adults, impaired synthesis of γ-globin or δ-globin chains can occur.

Although the switch from γ- to β-globin synthesis begins before birth, replacement of HbF by HbA occurs postnatally. Consequently, newborn infants with severe β-globin chain abnormalities are asymptomatic until 4-6 months of age. Complete absence of α-globin chains results in intrauterine failure and hydropic births, whereas fetuses with the lack or dysfunction of 3 α-genes, which is known as hemoglobin H (HbH) disease, will survive gestation.

Some mutations may also alter fetal to adult Hb switching, which occurs, for example, in hereditary persistence of HbF. Coinheritance of α- and γ-mutations as well as coinheritance of other hemoglobinopathies (eg, HbE, Hb Lepore, Constant Spring [CS], sickle cell hemoglobin, or HbS) may modify the clinical manifestation


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