Clinical variability and molecular characterization of Hbs/Gγ (Aγδβ)0-thal and Hbs/HPFH in Indian sickle cell disease patients: AIIMS experience

ABSTRACT Introduction: In sickle cell disease (SCD) patients, among the predictors of survival, HbF levels play a significant role in lowering the morbidity and mortality. Coinheritance of δβ thalassemia and hereditary persistence of fetal hemoglobin (HPFH) may contribute to variable HbF levels in SCD patients, thus influencing their clinicopathological profile. Such cases are sparsely documented in the literature and thus, we screened the presence of δβ thalassemia and HPFH in 126 cases of SCD with high HbF. Material and methods: A total 126 SCD individuals with raised HbF levels were the study subject. Capillary zone electrophoresis (CZE) was done for the quantitative assessment of hemoglobin variants. HbSC, HbSD, HbAS and HbSE cases were excluded. Asian Indian Gγ(Aγδβ)0-thal, δβ0-thal (Sicilian, 13.4？kb), (Chinese, 100？kb), HPFH-1 (Black, 106？kb), HPFH-2 (Ghanaian, 105？kb), HPFH-3 (Indian, 48.5？kb) were done by GAP-PCR. Results: Out of 126, 78 cases (62%) were homozygous for SCD. The remaining 48 cases suspected to be heterozygous were furthered screened and 6/48 cases (12.5%) were found to be compound heterozygous. Out of these 6 cases,4(66.66%) had HbS/ δβ- Gγ(Aγδβ)0 and 2(33%) had HbS/HPFH compound heterozygous condition. None of the patients had δβ0-thal (Sicilian, 13.4？kb), (Chinese, 100？kb), HPFH-1 (Black, 106？kb), HPFH-2 (Ghanaian, 105？kb). Conclusion: This study highlights the importance of understanding the complex patho-physiology of compound heterozygous cases of HbS/HPFH and HbS/δβ thalassemia, as these infrequent conditions lead to change in phenotype and clinical severity of the disease. Insight into more such cases will open the window to better analyze the disease pathogenesis in these rare compound heterozygous conditions, as this will be beneficial to formulate proper management protocol in these patients