Hb Kirikiriroa [α57(E6)Gly→Cys; HBA1: c.172G>T]: A Novel Unstable α-Globin Variant with Oxidized Derivatives Interfering with Hb A_1c

Abstract

We report the identification of a novel hemoglobin (Hb) variant [α57(E6)Gly→Cys; HBA1: c.172G>T], to be referred to as Hb Kirikiriroa. The variant was detected in five subjects from two families, with familial relationship established between the families following diagnosis. A persistently elevated Hb A_1c over a 1-year period prompted hemoglobinopathy screening in an adolescent male of New Zealand (NZ) European descent (case 1). Capillary electrophoresis (CE) revealed the variant was negatively charged and susceptible to oxidation, with multiple abnormal peaks detected (0.4–5.1% total Hb). Hb A_1c analysis by cation exchange high performance liquid chromatography (HPLC) was the first indication of the variant in a pregnant female of NZ European descent (case 2). Cases 1 and 2 had normal complete blood counts. Isopropanol stability testing provided evidence the variant was unstable. We herein describe the characterization of Hb Kirikiriroa and clinical significance of the variant for interference with Hb A_1c analysis by CE and cation exchange HPLC.

Keywords:

• Capillary electrophoresis (CE)
• glycated hemoglobin (Hb A_1c)
• high performance liquid chromatography (HPLC)
• unstable α-globin variant
• time-of-flight (TOF) mass spectrometry (MS)

Acknowledgments

The authors wish to acknowledge the Biochemistry Department at Waikato Hospital, and PathLab Hamilton, New Zealand, for undertaking the Hb A_1c analysis.

Disclosure statement

The authors report no conflict of interest. The authors alone are responsible for the content and writing of this article.