title: An intriguing high performance liquid chromatogram of a double heterozygosity for Hb Q-India/Hb D-Punjab.
abstract: Cation exchange high performance liquid chromatography (HPLC) is commonly utilized as the first method of screening for thalassemias and hemoglobinopathies worldwide. This method of diagnosis requires knowledge of the clinical background and complete blood counts as well as skill and experience in interpreting the sometimes complex results produced. An asymptomatic 27-year-old pregnant North Indian woman was found to have a highly unusual chromatographic pattern with multiple unexpected peaks during routine antenatal screening. Most concerning was a C-window peak as Hb C (HBB: c.19G>A) is rare in ethnic Asian Indian populations. Cellulose acetate electrophoresis at alkaline pH (8.6) and parental screening were performed. These revealed the correct diagnosis to be a double heterozygosity for Hb Q-India (HBA1: c.193G>C) (an uncommon asymptomatic α-globin chain variant) plus Hb D-Punjab (HBB: c.364G>C) (a β-globin chain variant that is common in this region and is asymptomatic in the heterozygous state). The unexpected C-window peak was the hybrid of the abnormal α-Q-India and β-D-Punjab globin chains. Another small peak was explained as a variant Hb A2 formed by the combination of α-Q-India and δ-globin chains. Hematopathologists should be cognizant of the complex pattern resulting from coinheritance of both α- and β-globin structural variants. Second-line testing and parental testing are invaluable in resolving unknown peaks, especially if rare or unexpected variants are being considered. Although both Hb Q-India and Hb D-Punjab are relatively common in northwestern India, to the best of our knowledge, only two recent reports describe a total of three cases of such diagnostically puzzling coinheritance.
authors.affiliation: Department of Haematology, Postgraduate Institute of Medical Education and Research , Chandigarh , India.
authors.forename: Rama Kumari
authors.initials: RK
authors.lastname: Badyal
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Chhabra
authors.forename: Prashant
authors.initials: P
authors.lastname: Sharma
authors.forename: Reena
authors.initials: R
authors.lastname: Das
mesh_terms: D000328:Adult; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005260:Female; D006580:Genetic Carrier Screening; D006455:Hemoglobins, Abnormal / Q000235:genetics / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D011296:Prenatal Diagnosis
chemical_list: D006455:Hemoglobins, Abnormal; C048600:hemoglobin Q India; C026237:hemoglobin D Punjab
keywords: Antenatal screening; Hb D-Punjab; Hb Q-India; cation exchange high performance liquid chromatography (HPLC); double heterozygous state; hematopathology; hemoglobinopathy; pattern recognition