Discordant Hba2 Expression In Hbs-Β Thalassemia: A Case Series Of Rare HPLC Phenotypes With Elevated Hbf

Abstract

Introduction

Sickle cell disease results due to substitution of single amino acid at the sixth position in the gene encoding the globin subunit for glutamic acid instead of valine producing an abnormal hemoglobin (Hb). Clinical picture of compound heterozygous Hb S beta thalassemia resembles thalassemia intermedia in addition to sickling features. Prognosis is better than thalassemia major or sickle cell anemia.

Case Series:

We report three sibling pairs (six children) who presented with fever and varying combinations of jaundice, cough, vomiting, and loose stools. Clinical examination revealed pallor with or without mild icterus. Laboratory investigations demonstrated severe anemia, with hemoglobin levels ranging from 1.5 to 3.0 g/dL. HPLC in all patients showed elevated HbS (40.5–56.3%) and HbF (21.4–39.2%) with HbA2 levels ranging from 2.0% to 3.8%, raising the differential diagnosis of homozygous sickle cell disease and compound heterozygous HbS/β-thalassemia. HPLC analysis of the parents in each family identified one parent with β-thalassemia trait and the other with sickle cell trait, confirming the diagnosis of compound heterozygous HbS/β-thalassemia in all six children.

Conclusion:

This case series highlights the importance of integrating HPLC findings with parental screening to differentiate compound heterozygous HbS/β-thalassemia from homozygous sickle cell disease. Early recognition of this condition enables appropriate clinical management, family counseling, and informed genetic risk assessment