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Diagnosis of thalassemia
The thalassemias are a group of autosomal recessive disorders of hemoglobin (Hb) synthesis. Normal adult Hb consists of 2 alpha globin chains (encoded by 2 pairs of alpha globin genes, each pair located on 1 of the chromosomes 16), and 2 beta globin chains (encoded by 2 beta globin genes, each located on 1 of the chromosomes 11). Thalassemia syndromes result from an underproduction of 1 or 2 types of globin chains and are characterized by the type (alpha, beta, delta) and magnitude of underproduction (number of defective genes) and the severity of clinical symptoms (minor, major). The severity of the clinical and hematologic effects is directly related to the number of genes deleted or affected.
The most common form of thalassemia is heterozygous alpha thalassemia 2, with 1 affected alpha globin gene. In heterozygous alpha thalassemia 2, there is no clinical effect and the blood count, including the mean cell volume, is normal. Heterozygous alpha thalassemia 1 and homozygous alpha thalassemia 2 (both with 2 affected genes) have the typical thalassemic picture (eg, hypochromic microcytic anemia, pallor, fatigue, shortness of breath, jaundice, and splenomegaly).
Hemoglobin H (Hb H) disease, having a deletion of 3 alpha chains, is a moderate-to-severe hemolytic disease. The severity of Hb H disease is related to the amount of Hb H in the red cells. The morphology of the red cells is often very bizarre due to denatured Hb found within the red cells.
The deletion of all 4 alpha chains is incompatible with life. Affected fetuses are hydropic and die in utero or shortly after premature birth. The blood smears show large hypochromic red cells, nucleated red cells, target cells, and red cell fragments. Hb Barts, Hb H, and Hb Portland are present in significant quantities. It is the most common cause of hydrops fetalis in Southeast Asia and southern China.
This consultative study tests for the detection of alpha-thalassemias, beta-thalassemias, delta-beta-thalassemia, and for Hb variants that are commonly accompanied by thalassemias: Hb H, Hb Lepore, Hb Barts, unstable Hb, hemolytic anemias, Hb E, hereditary persistence of high fetal Hb (several varieties), and combinations of Hb S with alpha- or beta-thalassemia, Hb E/beta-O-thalassemia, and many other complex thalassemic disorders. Some of the alpha-thalassemias (eg, Hb H disease) can be reliably identified by Hb electrophoresis alone; some require DNA probe studies. Since iron deficiency can mimic thalassemias, ferritin levels are measured to evaluate this possibility.
Definitive results and an interpretive report will be provided.
A hematopathologist expert in these disorders evaluates the case, appropriate tests are performed, and an interpretive report is issued.
DNA probe studies reveal deletional mutations that include most, but not all, alpha-thalassemias.
Hoyer JD, Hoffman DR: The thalassemia and hemoglobinopathy syndromes. In Clinical Laboratory Medicine. Second edition. Edited by KD McMlatchey. Philadelphia, Lippencott Williams and Wilkins, 2002, pp 866-892