Five Hemoglobin Variants in a Double Heterozygote for α- and β-Globin Chain Defects

Abstract

Genetic interactions of different defective globin chains could render laboratory diagnostics in a routine setting difficult. We report a hitherto undescribed condition of double heterozygosity for hemoglobin (Hb) Q-Thailand with α⁺-thalassemia and Hb Tak found in 2 adult Thai individuals. Both patients were healthy and had no pertinent past medical history. A complete blood count revealed slight elevations of Hb and HCT values with low MCV and MCH. Interestingly, Hb analysis demonstrated, in addition to Hb A, A₂, and F, as many as 5 Hb variants including Hb Tak (α^A₂β^Tak₂), Q-Thailand (α^QT₂β^A₂), QA₂ (α^QT₂δ₂), QF (α^QT₂γ₂), and a novel variant, Hb QTak (α^QT₂β^Tak₂). Hematological findings of these unusual cases were compared with those of pure heterozygotes for Hb Q-Thailand and Hb Tak found in our series. Hb analysis using combined HPLC and capillary electrophoresis did help in the initial recognition and in making presumptive diagnoses, but definite diagnoses of these cases with complex α- and β-hemoglobinopathies could only be obtained after DNA analysis.

Phenotype and Genotype in a Cohort of 312 Adult Patients with Nontransfusion-Dependent Thalassemia in Northeast Thailand

“…As for this complex thalassemia syndrome, Hb derivatives formed by interactions of other α- and β-globin chain defects are commonly encountered in the region. Careful consideration of Hb analysis results would help in the initial recognition of cases, but accurate diagnosis requires DNA testing [19]. …”

Frequency of unnecessary prenatal diagnosis of hemoglobinopathies: A large retrospective analysis and implication to improvement of the control program

“…They were at risk for Hb E-Hb Lepore or heterozygous Hb Lepore (n = 4), Hb E-Hb Tak (n = 3), Hb E-Hb Pyrgos (n = 2), Hb E-Hb J-Bangkok (n = 2), Hb E-Hb C (n = 1), Hb E-Hb Korle-Bu (n = 1), Hb E-Hb Hope (n = 1), Hb Hope-β 0 -thalassemia (n = 1), and Hb Tak-β 0 -thalassemia (n = 1). In fact, most of these Hb variants are clinically innocuous, even found in combination with Hb E or β-thalassemia [4,26,[34][35][36][37][38]. Association of Hb Tak with δβ 0 -thalassemia may alternatively lead to secondary erythrocytosis rather than severe thalassemia syndrome due to the high oxygen affinity characteristics of Hb Tak and Hb F [39].…”