Molecular and hematologic features of hemoglobin E heterozygotes with different forms of alpha-thalassemia in Thailand.

Abstract

We describe the hematological and DNA characterization of hemoglobin (Hb) E heterozygote with various forms of alpha-thalassemia in Thai individuals. Altogether, 202 unrelated adult subjects with Hb E heterozygotes either with or without alpha-thalassemia determinant were studied. The most prevalent interaction was found to be a double heterozygote for Hb E/alpha-thalassemia 2, followed by a double Hb E/alpha-thalassemia 1 and a Hb E/Hb Constant Spring (CS), even though the Hb CS was not detected. Double heterozygotes for Hb E and homozygous alpha-thalassemia 2 and Hb E with a compound alpha-thalassemia 2/Hb CS were also encountered with lower frequencies. Unexpectedly, as many as 18 cases previously diagnosed as Hb E carriers at routine Hb analysis were indeed Hb E heterozygotes with compound alpha-thalassemia 1/alpha-thalassemia 2, indicating a need for globin genotyping for accurate diagnosis. A change in Hb E level was observed which was related to a concomitant inheritance of alpha-thalassemia. The hematological expression of these Hb E heterozygotes with various forms of alpha-thalassemia, including a hitherto undescribed condition of double heterozygosity for Hb E/Hb Paksé identified in two subjects, is presented comparatively with those of the 80 cases of pure Hb E carriers. A multiplex allele-specific polymerase chain reaction (PCR) assay for simultaneous detection of Hb E and Hb CS genes is also described.