Hemoglobin Constant Spring (Hb CS) and Hb Paksé, two abnormal Hbs characterized by elongated alpha-globin chains resulting from mutations of the termination codon in the alpha2-globin gene, are the most prevalent nondeletional alpha-thalassemias in Southeast Asia. To determine the origins of these two variants in the region, we have determined alpha-globin gene haplotypes associated with these two variants on 120 Thai, eight Cambodian, and six Laos alleles, and the results were compared with those reported previously for the Chinese and Mediterranean. Five haplotypes were found to be associated with 131 alpha(CS) genes examined, whereas a single haplotype was linked to all the alpha(Paksé) genes in these Southeast Asian populations. All the alpha(CS) haplotypes differed from those of the Mediterranean, but one of them was similar to a Chinese alpha(CS) gene reported previously. It is concluded that there are multiple origins of the alpha(CS) and a single origin of the alpha(Paksé) mutations in Southeast Asia. Hematological findings confirm the mild thalassemia intermedia phenotypes for pure homozygous Hb CS and homozygous Hb CS with Hb E heterozygote and Hb E homozygote. The appearance of Hb CS peak by high-performance liquid chromatography analysis indicates the ability to form a tetrameric Hb molecule between the alpha(CS) and beta(E) chains, leading to a novel derivative with similar characteristics to Hb CS.

The capillary electrophoresis system could clearly demonstrate the presence of abnormal Hbs and provide useful information for presumptive diagnoses in most cases. The Hb analysis results could help in selection of appropriate DNA testing for final diagnoses of these variants.

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We describe haematological and DNA characterization of haemoglobinopathies in Thai adolescents caused by compound heterozygosities for Hb E [beta26(B8) Glu-Lys] and two other beta-globin chain variants, Hb Pyrgos [beta83(EF7) Gly-Asp] and Hb J Bangkok [beta56(D7) Gly-Asp]. Hb analysis demonstrated that although these two beta-chain variants have separated elution profiles on liquid chromatography-based Hb analysis, they have similar alkaline electrophoretic mobilities on cellulose acetate electrophoresis. Haematological data associated with these two previously undescribed conditions were compared with those of pure carriers of the variants found in other unrelated Thai individuals. beta-Globin gene haplotypes linked to these two beta-chain variants and a simple DNA testing based on multiplex allele-specific polymerized chain reaction for differential diagnosis are presented.

Secondary erythrocytosis may arise from several causes, but an association with oxygen transport is rare. We describe for the first time a form of secondary erythrocytosis caused by compound heterozygosity for hemoglobin (Hb) Tak and (δβ)⁰-thalassemia found in an adult Thai individual. The patient had marked erythrocytosis and microcytosis with increased Hb and hematocrit values. Hb analyses using the Hb Gold Analyzer showed Hb A₂ (72.5%) and Hb F (30.0%) without Hb A while the capillary electrophoresis revealed 2.3% Hb A₂ and a major peak of Hb F (91.2%). Further molecular investigation identified that he was in fact a compound heterozygote for Hb Tak and deletional (δβ)⁰-thalassemia. Hematological parameters of the patient were compared with those observed for a Thai boy who demonstrated features of erythrocytosis and microcytosis caused by homozygous Hb Tak with α⁺-thalassemia and with those of pure carriers of Hb Tak and (δβ)⁰-thalassemia in our series. This report confirms the importance of both Hb and molecular investigations for the assessment of genotype/phenotype correlation and the appropriate management of the patients.