Molecular and hematologic features of hemoglobin E heterozygotes with different forms of ?-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.

Effect of the maternal βE-globin gene on hematologic responses to iron supplementation during pregnancy

“…We have shown previously that hematologic variables of nonpregnant subjects with Hb E are significantly different from those of nonthalassemic pregnant subjects (17,18). The finding in the present study that pregnant women with ␤ E -globin gene have hematologic values different from women who are not carriers of this gene (Table 3) was therefore not unexpected.…”

“…Because of the heterogeneity of thalassemia and hemoglobinopathies in Southeast Asia (17,18,27), interaction of Hb E with various forms of ␣-thalassemia was unexpectedly observed in our study sample, most of which had heterozygous Hb E coinherited with ␣ ѿ -thalassemia. Other interactions with less frequency included heterozygous Hb E coinherited with either ␣ 0 -thalassemia, Hb CS, Hb Pakse', or homozygous ␣ ѿ -thalassemia.…”

α⁰-Thalassemia and Related Disorders in Northeast Thailand: A Molecular and Hematological Characterization

“…Other remaining subjects included 538 (34.9%) Hb E cases, 173 β-thalassemia cases, 140 (9.8%) α + -thalassemia carriers and 293 (19.0%) nonhemoglobinopathy cases. As expected, genetic interactions of Hb E with various forms of α-thalassemia were observed for this group of Thai population, as has been noted previously [16, 17]. In this study, only subjects with α⁰-thalassemia were further analyzed and presented.…”

“…As expected, a lower proportion of Hb E in group 2 (19.7 ± 3.3%) for heterozygous Hb E was observed. This low level of Hb E should represent the effect of a decreased availability of α-chains on the αβ E subunit formation [16,17,18]. Data in group 3 also indicate that interaction of heterozygous α⁰-thalassemia with homozygous Hb E is not associated with more severe disease.…”

High Frequency of α-Thalassemia in the So Ethnic Group of South Laos

“…High frequencies of α-thalassemia 1 of the Southeast Asian type (– SEA ), α-thalassemia 2 (–α) and Hb Constant Spring (Hb CS) [α 2 142 TAA → CAA] are present in many populations of Southeast Asia [1,2,3,4,5,6,7,8]. Recently, another electrophoretically slow-moving hemoglobin due to a term codon mutation, Hb Paksé (Hb PS) [α 2 142 TAA → TAT], was observed in Laos and Northeastern Thailand [8, 9]. The prevalence of these anomalies has medical and public health implications: homozygosity for α-thalassemia 1 leads to fetal death due to hydrops fetalis, and compound heterozygosity of α-thalassemia 1 with one of the α 2 -globin gene mutations causes Hb H disease.…”