The diverse molecular basis and hematological features of Hb H and AEBart's diseases in Northeast Thailand.

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 alpha-thalassemia 1 (SEA type) with the Hb Constant Spring (Hb CS; 35 of 52 patients), followed by the deletion of three alpha-globin genes with the SEA type alpha-thalassemia 1 and the 3.7- or 4.2-kb deletion of alpha-thalassemia 2 (14 of 52 patients) and the interaction of the SEA alpha-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 alpha-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 alpha-thalassemia 1 and an alpha2 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 alpha-thalassemia 2 produced a more severe phenotype than that of the deletional one. Therefore, alpha-globin gene analysis of Hb H and AEBart's disease patients would be useful for predicting the clinical outcome and improving genetic counseling. Copyright 2004 S. Karger AG, Basel