Challenges in prenatal diagnosis and genetic counselling in compound heterozygosity for beta thalassemia and hereditary persistence of fetal hemoglobin (HPFH)

Abstract

Background

Elevated levels of Fetal hemoglobin (HbF) in pregnancy can raise significant challenges in diagnosis and approach. We share an interesting clinical scenario to discuss the importance of increased HbF during pregnancy and effective genetic counselling.

Case report

A 29 years old primigravida presented at 16 weeks for routine antenatal care. Her HbF levels were elevated at 14.5 % and high performance liquid chromatography (HPLC) of her partner revealed HbA2 levels of 5.6 % and HbF levels of 0.8 %. HPLC findings suggested a possible diagnosis of either heterozygosity for delta-beta thalassemia or hereditary persistence of HbF in the mother and beta thalassemia trait in the father. Hemoglobinopathy gene panel sequencing was performed for the father, mother and fetus, while Multiplex Ligation-Dependent Probe Amplification (MLPA) testing was conducted for the mother and fetus. The HBB gene sequencing revealed a heterozygous c.27_28insG mutation in both the father and fetus. The MLPA test on the mother found a heterozygous deletion of the HBB to HBG1 (HBB, HBD, HBBP, and HBG1) region, also present in the fetus. This indicated that the fetus had both a point mutation and a deletion in a compound heterozygous state, suggesting a high likelihood of being affected by beta thalassemia major or intermedia. Comprehensive genetic counselling was done. After understanding the genetic scenario, the couple chose to terminate the pregnancy.

Conclusion

HPLC can efficiently screen for hemoglobinopathies, but comprehensive molecular investigations are essential for precise diagnosis and optimal medical care. Practical genetic counselling aids couples in making informed decisions about future pregnancies.