Co-inheritance of α⁰ -thalassemia elevates Hb A₂ level in homozygous Hb E: Diagnostic implications

Differentiation of homozygous hemoglobin (Hb) E with and without α⁰ -thalassemia is subtle on routine hematological ground. We examined in a large cohort of homozygous Hb E if the level of Hb A₂ is helpful.

A total of 592 subjects with homozygous Hb E were recruited from ongoing thalassemia screening program. Additionally, five couples at risk of having fetuses with Hb Bart's hydrops fetalis who were homozygous Hb E were also investigated. Hb analysis was performed using capillary electrophoresis system. Globin genotypes were defined by DNA analysis.

Subjects were classified into four groups including pure homozygous Hb E (n=532), homozygous Hb E/α⁰ -thalassemia (n=48), Hb Constant Spring EE Bart's disease (n=8), and Hb EE Bart's disease (n=4). The levels of Hb A₂ were found, respectively, to be 4.97±0.69, 6.64±1.02, 4.86±0.87, and 7.60±1.04%. Among five couples at risk, α⁰ -thalassemia was identified in three subjects with Hb A₂ >6.0%.

Increased Hb A₂ level is a useful marker for differentiation of homozygous Hb E with and without α⁰ -thalassemia. This should lead to a significant reduction in number of referral cases of homozygous Hb E for molecular testing of α⁰ -thalassemia in routine practice.