Problems in determining thalassemia carrier status in a program for prevention and control of severe thalassemia...

Prevention and control of severe β thalassemia by carrier detection and identification of couples at risk in developed countries is one of the most successful stories in modern medicine. Similar programs in developing countries especially Southeast Asia, are more problematic because both α and β thalassemias are highly prevalent. In Thailand, there are limited data on whether we could determine, based on hematological phenotypes, the mutation severity and/or coinheritance of α thalassemia in β thalassemia traits.

Comprehensive molecular, hematology and hemoglobin analyses of the α and β globin genes were performed in 141 healthy individuals identified as β thalassemia carriers.

Seventeen different β globin mutations were successfully identified out of all cases analyzed. Although the majority of the mutations identified were the β⁰ or severe β⁺ thalassemia alleles, a high proportion of mild mutations (25%) was observed. Of these β thalassemia traits, 22.3% were found to co-inherit the α thalassemias. Milder hematological phenotypes were noted in β⁺ compared with β⁰ thalassemia traits when the α globin genes were intact. Although co-inheritance of α⁰ thalassemia might be suspected in cases with skewed profiles, due to the overlapping values, it remains difficult to apply these parameters for reliable carrier determination.

A combination of hemoglobin analysis and DNA testing seems to be the best way to confirm carrier status in a region with high frequency for both α and β thalassemias. Underdiagnoses of carrier status could hamper the effectiveness of a thalassemia prevention and control program.