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Ultra-rare Hb Regina (HBB:c.289C>G) with coinherited β-thalassaemia trait: solving the puzzle for extreme erythrocytosis
  1. Nabhajit Mallik1,
  2. Manu Jamwal1,
  3. Ritika Sharma1,
  4. Namrata Singh1,
  5. Prashant Sharma1,
  6. Deepak Bansal2,
  7. Amita Trehan2,
  8. Sanjeev Chhabra1,
  9. Reena Das1
  1. 1Department of Hematology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
  2. 2Department of Pediatrics (Hematology-Oncology Unit), Post Graduate Institute of Medical Education and Research, Chandigarh, India
  1. Correspondence to Professor Reena Das, Department of Hematology, Post Graduate Institute of Medical Education and Research, Chandigarh, India; reenadaspgi{at}hotmail.com

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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 5

Protein-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 …

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Footnotes

  • Handling editor Mary Frances McMullin.

  • Contributors PS, RD and NM designed the study. MJ, RS and NS performed the next-generation sequencing and analysed the data. SC performed the Hb HPLC/electrophoresis. DB and AT were involved in the clinical management of the patient. NM wrote the manuscript and all the coauthors reviewed and approved the final version of the manuscript.

  • Funding PGIMER’s Medical Education and Research Cell vide sanction letter number 71/2-Edu-16/209 dated 10 January 2018.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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