Alpha-thalassemia
| Overview |
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- Alpha-thalassemia is a subtype of thalassemia characterized by reduced synthesis of the alpha-globin chain, resulting in a relative excess of beta-globin within erythrocytes. See the thalassemia page for a general discussion of these disorders.
| Genetics |
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- Alpha-globin is coded on two consecutive genes on Chromosome 16, meaning each diploid erythrocyte precursor carries four total alpha-globin alleles. Individuals with alpha-thalassemia carry deletions that affect any combination of these loci, meaning there might be absent synthesis from one, two, three, or all four alpha-globin loci.
| Incidence |
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- Deletions of the alpha-globin gene is most frequently encountered in Asian and African American populations.
| Pathogenesis |
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- Reduced synthesis of alpha-globin results in a relative excess of beta-globin chain production as well as reduced total production of hemoglobin. The reduced total hemoglobin production yields the classic microcytic anemia of thalassemia. However, a relative excess of beta-globin production yields hemoglobin tetramers composed entirely of beta-globin tetramers, known as Hb H. Although Hb H is somewhat soluble, it is more easily oxidized and has a higher affinity for oxygen than the normal Hb A. Not only does this make for inefficient oxygen delivery to tissues, but also oxidized Hb H tends to accumulate in erythrocytes, yielding an extravascular hemolytic anemia and thus splenomegaly. Hb H also appears to induce a certain degree of ineffective erythropoiesis. The degree of these biochemical defects and thus the intensity of clinical consequences depends on the number of alpha loci affected as described below.
| Clinical and Laboratory Consequences |
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- Overview
- Given the four loci of alpha-globin, four possible alpha-thalassemia syndromes can result depending on what number of loci are affected.
- One deletion: Silent Carrier
- Patients with only one alpha-globin deletion are asymptomatic and typically do not display anemia or microcytosis.
- Two deletions: Alpha-thalasemia Minor
- Patients with two alpha-globin deletions are still asymptomatic but typically display a microcytic anemia on laboratory examination.
- Three deletions: Hb H Disease
- Patients with three alpha-globin deletions display a symptomatic microcytic anemia with moderate extravascular hemolysis that may yield splenomegaly. Most patients survive to adult life and only become transfusion-dependent in their later years.
- Four Deletions: Hydrops Fetalis
- Deletion of all four alpha-globin chains is not compatible with life and results in hydrops fetalis.
