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Detection of zeta-globin chains in the cord blood by ELISA (enzyme-linked immunosorbent assay): rapid screening for alpha-thalassemia 1 (Southeast Asian type).

Fetuses with homozygous alpha-thalassemia 1, in which the deletion of all four alpha-globin genes results in the absence of any alpha-globin chains, are severely anemic with clinical features of hydrops fetalis. Definitive diagnosis of alpha-thalassemia 1 carriers is difficult since there are few red cell abnormalities. Recently Chui et al. found that minute amounts of embryonic zeta-globin chains are present in adult hemoglobin of the Southeast Asian type of alpha-thalassemia 1 carriers. In this study, we screened 521 cord bloods for alpha-thalassemia 1. Hemoglobin analysis, including quantitation of Hb Bart's, was performed using the automated HPLC, alpha-thalassemia short program (VARIANT, Bio-Rad, Hercules, CA). Of these, 200 cord blood samples in which Hb Bart's was demonstrated were tested for the presence of zeta-globin chains by ELISA using labeled anti-zeta monoclonal antibody. Zeta-globin ranged between 0.21 and 0.83% in 19 specimens carrying alpha-thalassemia 1 gene. In the remaining 90 out of 109 specimens in which Hb Bart's was greater than 1.2%, zeta-globin was less than 0.17%. DNA analysis revealed the presence of normal alpha-genotype and other types of alpha-thalassemia including alpha-thalassemia 2 and Hb Constant Spring. One false positive was found in which the zeta-globin was 0.25% by ELISA but in which PCR indicated an alpha-thalassemia 2 heterozygote. Ninety-one samples with Hb Bart's of less than 1.2% by HPLC are most likely normal with a zeta-globin range between 0 and 0.14%. This study also showed that the frequency of alpha-thalassemia 1 in Bangkok is 3.65%.