The thalassemia syndromes are inherited disorders characterized by reduced Hgb synthesis associated with mutations in either the α- or β-gene of the molecule (Table 21-3).
|Genotype||Hemoglobin (g/dL)||Mean Cellular Volume (fL)||Transfusion Dependent|
|Trait||α−/α− or αα/−−||>10||<80||No|
|Hydrops fetalis||−−/−−||Incompatible with life|
|β-Thal minor (trait)||β/β0||>10||<80||No|
|β-Thal major||β+/β0 or β0/β0||<7||<70||Yes|
β+, β-thalassemia genes produce some β-globin chains but with impaired synthesis; β0, β-thalassemia genes produce no β-globin chains.
- β-Thalassemia results in a decreased production of β-globin and a resultant excess of α-globin, forming insoluble α-tetramers and leading to ineffective erythropoiesis.
- β-Thalassemia minor (trait) occurs with one gene abnormality with underproduction of β-chain globin. Patients are asymptomatic and present with microcytic, hypochromic RBCs and Hgb levels >10 g/dL.
- β-Thalassemia intermedia (non–transfusion-dependent) occurs with dysfunction in both β-globin genes so that anemia is more severe (Hgb 7–10 g/dL).
- β-Thalassemia major (Cooley anemia or transfusion-dependent) is caused by mutations of both β globin genes that fail to produce significant amounts of β-globin and generally require lifelong RBC transfusion support.
- α-Thalassemia occurs with a deletion of one or more of the four α-globin genes, leading to a β-globin excess.
- Mild microcytosis and mild hypochromic anemia (Hgb >10 g/dL) are seen with the loss of one or two α-globin genes (silent carrier and α-thal trait).
- Deletion of three α-globin genes (Hgb H disease) results in splenomegaly and hemolytic anemia. In patients with Hgb H disease, transfusion or splenectomy is often not necessary until after the second or third decade of life. In addition, oxidant drugs similar to those that exacerbate glucose-6-phosphate dehydrogenase (G6PD) deficiency should be avoided because increased hemolysis may occur.
- Hydrops fetalis occurs with the loss of all four α-globin genes and is incompatible with life.
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