Elevated Hb A2 Levels in a Patient with a Compound Heterozygosity for the (β+) −31 (A > G) and (β0) Codon 17 (A > T) Mutations Together with a Single α-Globin Gene

Abstract

We report the molecular and hematological feature of a Thai woman who had clinical diagnosis of β-thalassemia intermedia (β-TI). Hemoglobin (Hb) high performance liquid chromatography (HPLC) analysis identified Hb A (64.4%), Hb F (12.3%) and Hb A2/E (15.9%) with small peaks of Hb Bart’s (γ4) and Hb H (β4). She was initially diagnosed as EA Bart’s disease, which occurs from combination of Hb H disease and Hb E (HBB: c.79G > A) trait. However, the Hb analysis using capillary electrophoresis (CE) demonstrated no Hb E, 68.5% Hb A, 15.5% Hb F and 16.0% Hb A2. DNA analysis showed a compound heterozygosity for (β+) −31 (A > G) (HBB: c.-81A > G) and (β0) codon 17 (A > T) (HBB: c.52A > T) mutations and deletional Hb H (– –SEA/–α3.7). Thus, she was finally diagnosed with a combination of Hb H disease and compound heterozygosity of β+/β0-thalassemia (β+/β0-thal). The β-globin mutations could affect not only hematological parameters but also elevate the Hb A2 levels. These effects could not be ameliorated by the coinheritance of Hb H disease. Therefore, a better understanding of the effects of this combination on hematological analysis data will be useful for providing accurate diagnosis, genetic counseling, prevention and control programs of β-thalassemia major (β-TM).