α-thalassemia in affected fetuses with hemoglobin E-β-thalassemia disease in a high-risk population in Thailand.

Objectives: A co-inheritance of α-thalassemia can ameliorate the clinical severity of the hemoglobin (Hb) E-β-thalassemia disease. This information should be provided at prenatal diagnosis. Identification of α-thalassemia in an affected fetus is therefore valuable. We have explored this genetic interaction in a large cohort of affected fetuses with hemoglobin (Hb) E-β-thalassemia in northeast Thailand.

Methods: A study was done retrospectively on 1,592 couples at risk of having fetuses with Hb E-β-thalassemia, encountered from January 2011 to December 2019. A total of 415 left-over DNA specimens of the affected fetuses with Hb E-β-thalassemia disease were further investigated. Examination of α-thalassemia was done using gap-PCR or a multiplex PCR assay for simultaneous detection of Hb E and α-thalassemia mutations.

Results: Of the 415 affected fetuses, the two most common β-thalassemia genes found were the codons 41/42 (-TTCT) (199/415; 48.0%) and codon 17 (A-T) (115/415; 27.7%). α-thalassemia was found unexpectedly in 21 (5.1%) fetuses. Hematologic phenotypes of the parents indicated that it was impossible to differentiate a pure β-thalassemia carrier from a double β-thalassemia/α-thalassemia heterozygote unless DNA analysis is performed. In contrast, a reduced level of Hb E in the Hb E carrier (<25%) is a valuable marker for predicting double heterozygosity for Hb E/α-thalassemia. This could be further confirmed using a multiplex PCR assay.

Conclusions: There is a high prevalence of co-inheritance of α-thalassemia in fetuses with Hb E-β-thalassemia disease. In a high-risk population such as Thailand, we recommend screening for α-thalassemia in all affected fetuses with Hb E-β-thalassemia disease and providing complete genetic information to the parents to make appropriate decisions at prenatal diagnosis and genetic counseling.