TY - JOUR T1 - Ultra-rare Hb Regina (<em>HBB</em>:c.289C&gt;G) with coinherited β-thalassaemia trait: solving the puzzle for extreme erythrocytosis JF - Journal of Clinical Pathology JO - J Clin Pathol DO - 10.1136/jclinpath-2021-208013 SP - jclinpath-2021-208013 AU - Nabhajit Mallik AU - Manu Jamwal AU - Ritika Sharma AU - Namrata Singh AU - Prashant Sharma AU - Deepak Bansal AU - Amita Trehan AU - Sanjeev Chhabra AU - Reena Das Y1 - 2022/01/17 UR - http://jcp.bmj.com/content/early/2022/01/17/jclinpath-2021-208013.abstract N2 - High oxygen-affinity haemoglobins (Hb) are among the earliest recognised molecular defects in patients with inherited forms of erythrocytosis, and several α-globin and β-globin chain variants have been reported.1 2 Their diagnostic workup typically involves SpO2 and erythropoietin measurement to distinguish primary from secondary erythrocytosis, followed by exclusion of acquired causes, and subsequently, phenotypic tests like high-performance liquid chromatography (HPLC), isoelectric focusing, capillary electrophoresis, and alkaline pH electrophoresis and demonstration of a low p50 on an oxygen-saturation curve. Clinical laboratories that lack facilities for oxygen-saturation curve analysis may calculate the p50 mathematically using venous blood gas analysis parameters.3 Genetic confirmation is often also straightforward using direct DNA sequencing of the relatively small globin genes by Sanger’s method.1 4 5Protein-separation techniques like HPLC/electrophoresis can detect less than 50% of the high oxygen-affinity Hb variants, primarily those with electrostatic charge alterations due to amino acid substitutions.6 However, they cannot distinguish variants with isoelectric substitutions. We report here a set of siblings in whom the interaction of ultra-rare high oxygen-affinity Hb with a relatively common β-thalassemic variant led to diagnostic confusion as well as resulted in astonishingly high erythrocyte counts.Two Sikh brothers were referred for the evaluation of long-standing unexplained erythrocytosis. The older sibling (now in his early 20s) gave a history of stroke and seizures during infancy with complete recovery by 1 year … ER -