Compound Heterozygosity for Haemoglobin D Punjab and Haemoglobin Q India: A Rare Case Report

Haemoglobin variants constitute an important group of inherited disorders with variable clinical and haematological manifestations. The co-existence of structural variants involving both α and β globin chains is uncommon and may present diagnostic challenges during routine haemoglobinopathy screening. The authors hereby report a rare case of compound heterozygosity for haemoglobin D Punjab and haemoglobin Q India identified during haemoglobin variant analysis. A 19-year-old Sindhi unmarried woman was referred for haemoglobinopathy evaluation during investigation for menstrual irregularities. High-Performance Liquid Chromatography (HPLC) performed on the Bio-Rad D-10 system demonstrated a reduced Haemoglobin (HbA0) fraction (50.4 percent) with normal HbA2 (2 percent). A prominent peak of 25 percent at a retention time of 3.94 minutes suggestive of HbD Punjab, while an additional 13.7 percent peak at 4.66 minutes was suggestive of HbQ India. An intermediate 8.1 percent peak eluting in the HbC window was interpreted as a hybrid fraction produced by interaction between the two variants. Molecular confirmation using bidirectional Sanger sequencing identified heterozygous variants in both the β globin gene {Haemoglobin Subunit Beta (HBB) c.364G>C; p.Glu122Gln} and the α globin gene (HBA1 c.193G>C; p.Asp65His), confirming compound heterozygosity for HbD Punjab and HbQ India. The patient demonstrated mild microcytic anaemia without clinical features of haemolysis. Recognition of the characteristic HPLC pattern is important because the hybrid fraction may mimic HbC and lead to diagnostic confusion. Although this genotype is usually clinically benign, accurate identification is essential for genetic counselling and family screening.