The Diverse Molecular Basis and Hematological Features of Hb H and AEBart’s Diseases in Northeast Thailand

Abstract

We defined the molecular basis and correlated the hematological phenotypes with the globin genotypes in 52 patients with Hb H disease and 29 patients with AEBart’s disease of northeast Thailand. Among the former group, the most prevalent molecular defect was found to be the interaction of α-thalassemia 1 (SEA type) with the Hb Constant Spring (Hb CS; 35 of 52 patients), followed by the deletion of three α-globin genes with the SEA type α-thalassemia 1 and the 3.7- or 4.2-kb deletion of α-thalassemia 2 (14 of 52 patients) and the interaction of the SEA α-thalassemia 1 with the Hb Paksé which was found in the remaining 3 patients. Among the 29 patients of the latter group, in 18 disease was caused by interactions of Hb E heterozygotes with the SEA α-thalassemia 1 and Hb CS. Interaction of Hb E heterozygotes with a deletional form of Hb H disease was detected in 7 patients and the Hb Paksé AEBart’s disease was found in another 3 patients. A remaining patient with an unusually severe form of AEBart’s disease with a lower Hb E level and observable Hb H was associated with a hitherto undescribed condition, the interaction of Hb E heterozygote with α-thalassemia 1 and an α2 codon 30 (GAG) deletion. Hematological characterization of the patients demonstrated that although disease in most of them was associated with thalassemia intermedia phenotypes, it was apparent that association with the nondeletional form of α-thalassemia 2 produced a more severe phenotype than that of the deletional one. Therefore, α-globin gene analysis of Hb H and AEBart’s disease patients would be useful for predicting the clinical outcome and improving genetic counseling.

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

“…Previous studies have demonstrated that interaction of α⁰-thalassemia and α + -thalassemia (which results in the Hb H disease) with heterozygous Hb E (Hb H/Hb E heterozygote) and homozygous Hb E (Hb H/Hb E homozygote) usually leads to complex αβ-thalassemia syndromes known as EABart’s and EFBart’s diseases, respectively [4]. Both diseases are usually accompanied by severe thalassemia intermedia phenotypes with detectable Hb F (α 2 γ 2 ) and Hb Bart’s (γ 4 ) due to an increased expression of the γ-globin gene [4, 5]. As shown in table 1, in these 2 groups, microcytosis and hypochromicity were more pronounced than in groups 1–6, and only modest elevation of Hb F was observed (3.0 ± 2.2 to 6.5 ± 3.6%).…”

“…The disease also carries an increased risk of maternal complications with severe preeclampsia, ante- and postpartum hemorrhage and lethal complications [3]. In addition, interaction of α⁰-thalassemia with α + -thalassemia leads to Hb H disease, and interaction of Hb H disease with Hb E can lead to complex αβ-thalassemia intermedia syndromes [4, 5]. Therefore, identification of α⁰-thalassemia carriers is an important step in genetic counseling, prevention and control of thalassemia in at-risk families.…”

Thalassemia and hemoglobinopathies in an ethnic minority group in Central Vietnam: implications to health burden and relationship between two ethnic minority groups

“…Previously described gap-PCR and allele specific PCR (ASPCR) were used to identify six forms of α-thal mutations common in Southeast Asia, including SEA (NG_000006.1: g.26264_45564del19301) and THAI (NG_000006.1: g.10664_44164del33501) deletions causing α 0 -thal, −3.7 (NG_000006.1:g.34164_37967del3804) and −4.2 kb (exact deletion breakpoints are not available) deletions causing α + -thal, Hb CS (HBA2:c.427T>C), and Hb Ps (HBA2: c.429A > T) (Sanchaisuriya et al 2002;Fucharoen et al 2003;Boonsa et al 2004;Sae-ung et al 2006). Based on our experience of using these methods in routine practice, the false negative rate was less than 0.1%.…”

Routine screening for α-thalassaemia using an immunochromatographic strip assay for haemoglobin Bart's

“…In addition, co-inheritance of a-thalassaemia with b-thalassaemia can ameliorate the clinical severity of b-thalassaemia disease. [3][4][5][6] Identification of athalassaemia is essential for providing appropriate genetic thalassaemia counselling to patients.…”