Hemoglobin variant in disguise

V Higgins; L MacNeil; I Sosova; R Ridsdale; A Bruce; D Brinc; W David; J Rara; P Bordeleau; M P Estey; M L Parker; O Ismail; T Agbor

doi:10.1016/j.clinbiochem.2023.110589

Hemoglobin variant in disguise

Clin Biochem. 2023 Aug:118:110589. doi: 10.1016/j.clinbiochem.2023.110589. Epub 2023 May 24.

Authors

V Higgins¹, L MacNeil², I Sosova³, R Ridsdale², A Bruce⁴, D Brinc⁵, W David⁶, J Rara⁶, P Bordeleau⁷, M P Estey⁸, M L Parker⁸, O Ismail⁸, T Agbor⁸

Affiliations

¹ DynaLIFE Medical Labs, Edmonton, AB, Canada; Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada. Electronic address: victoria.higgins@dynalife.ca.
² Newborn Screening Laboratory, Alberta Precision Laboratories, University of Alberta Hospital, Edmonton, AB, Canada; Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada.
³ Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada; Newborn Screening Laboratory, Alberta Precision Laboratories, University of Alberta Hospital, Edmonton, AB, Canada.
⁴ Division of Oncology and Hematology, Stollery Children's Hospital, Edmonton, AB, Canada; Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.
⁵ University Health Network, Department of Clinical Biochemistry, Toronto, ON, Canada; University of Toronto, Department of Laboratory Medicine and Pathobiology, Toronto, ON, Canada.
⁶ Department of Hematology and Flow Cytometry, University Health Network, Toronto, ON, Canada.
⁷ DynaLIFE Medical Labs, Edmonton, AB, Canada.
⁸ DynaLIFE Medical Labs, Edmonton, AB, Canada; Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada.

PMID: 37236295
DOI: 10.1016/j.clinbiochem.2023.110589

Abstract

Background: Hemoglobinopathies include thalassemia syndromes, where production of one or more globin subunits of hemoglobin (Hb) is reduced, and structural Hb variants. Over 1000 disorders of Hb synthesis and/or structure have been identified and characterized, with phenotypes ranging from having severe clinical manifestations to clinically silent. Various analytical methods are used to phenotypically detect Hb variants. However, molecular genetic analysis is a more definitive method for Hb variant identification.

Case report: Here, we report a case of a 23-month-old male with results from capillary electrophoresis, gel electrophoresis (acid and alkaline), and high-performance liquid chromatography most consistent with HbS trait. Specifically, capillary electrophoresis showed slightly elevated HbF and HbA2, HbA of 39.4% and HbS of 48.5%. The HbS percentage was consistently higher than expected (typically 30-40%) for HbS trait with no concurrent thalassemic indices. The patient has not experienced any clinical complications due to the hemoglobinopathy and he is thriving.

Conclusion: Molecular genetic analysis revealed the presence of compound heterozygosity for HbS and Hb Olupona. Hb Olupona is an extremely rare beta-chain variant that appears as HbA on all three common methods used for phenotypic Hb analysis. When the fractional concentration of Hb variants is unusual, more definitive methods should be used, such as mass spectrometry or molecular genetic testing. In this case, incorrectly reporting this result as HbS trait is unlikely to have a significant clinical impact, as current evidence suggests Hb Olupona is not a clinically significant variant.

Keywords: Hb Olupona; Hemoglobin variant; Hemoglobinopathy; Sickle cell trait.

Publication types

Case Reports

MeSH terms

Electrophoresis, Capillary / methods
Hemoglobin A2
Hemoglobinopathies* / diagnosis
Hemoglobinopathies* / genetics
Hemoglobins, Abnormal* / genetics
Humans
Male
Thalassemia* / genetics

Substances

Hemoglobins, Abnormal
Hemoglobin A2