In normal subjects, globin chain synthesis for hemoglobin is very tightly controlled, such that the ratio of alpha to non-alpha chains is 1:1. Thalassemia refers to a spectrum of diseases characterized by reduced or absent production of one of the globin chains of hemoglobin. Specifically, beta thalassemia is due to impaired production of beta globin chains, which leads to a relative excess of alpha globin chains. Excess alpha globin chains are unstable, incapable of forming soluble tetramers on their own, and precipitate within the cell, leading to a variety of clinical manifestations. The degree of alpha globin chain excess determines the severity of subsequent clinical manifestations, which are profound in patients homozygous for impaired beta globin synthesis and much less pronounced in heterozygotes, who generally have minimal or mild anemia and no symptoms. (See "Pathophysiology of beta thalassemia".)
The management of beta thalassemia will be reviewed here [1,2]. The clinical manifestations of this disorder are discussed separately. (See "Clinical manifestations and diagnosis of the thalassemias".)
Certain clinical terms are used to describe the phenotypic expression of beta thalassemia (see "Pathophysiology of beta thalassemia"):
●Beta (0) thalassemia – Beta (0) thalassemia refers to mutations of the beta globin locus that result in the absence of production of beta globin. Patients homozygous or doubly heterozygous for beta (0) thalassemic genes cannot make normal beta chains and are therefore unable to make any hemoglobin A.
●Beta (+) thalassemia – Beta (+) thalassemia refers to mutations that result in decreased production of beta globin. Patients homozygous for beta (+) thalassemic genes are able to make some hemoglobin A, and are generally less severely affected than those homozygous for beta (0) genes.