Missing Hb Q-India Peak in a Triple-Heterozygous Patient with Hb D-Punjab/Hb Q-India/β-Thalassemia Trait

Abstract

Interpretation of variant hemoglobins (Hbs) can pose challenges. We describe a puzzling case with multiple variant Hb peaks that was solved by family studies. A 32-year-old female with anemia and jaundice underwent cation exchange high performance liquid chromatography (HPLC), which revealed near-absence of Hb A along with variant peaks in the D- and C-windows (78.9 and 13.3%, respectively) and normal range of Hb F. As the HPLC did not fit any known pattern, family screening was performed. Her mother was heterozygous for Hb D-Punjab (HBB: c.364G>C) and Hb Q-India (HBA1: c.193G>C) with the hybrid αQ-India/βD-Punjab eluting in the C-window on HPLC. Her sister had β-thalassemia (β-thal) trait, while her brother was heterozygous for Hb Q-India. In view of the family study results, the index case was interpreted as a double heterozygote for Hb D-Punjab and β-thal with coinherited Hb Q-India. The Hb Q-India peak [retention time (RT) 4.7 min.] was absent on her HPLC as there were no normal β-globin chains available to bind with the αQ-India chains. To the best of our knowledge, such an HPLC pattern with a missing Q-India peak, despite having inherited the αQ-India variant, has not been previously reported. This case illustrates the importance of family screening as an inexpensive and rapid method to resolve difficult and unusual HPLC patterns.