Hb Kalundborg [β79(EF3)Asp→Glu; HBB: c.240C>a], a Possible Low-affinity Hemoglobin Variant Detected during Hb A1c Measurement

Hemoglobin. 2022 Mar;46(2):124-128. doi: 10.1080/03630269.2022.2079520. Epub 2022 Aug 3.

Abstract

A previously unknown hemoglobin (Hb) variant was detected during measurement of glycosylated Hb (Hb A1c) after the introduction of a new high performance liquid chromatography (HPLC) apparatus. Subsequent DNA sequencing revealed a heterozygous single nucleotide substitution at codon 79 (C>A) on the β-globin gene changing an amino acid [β79(EF3)Asp→Glu; HBB: c.240C>A]. The new Hb variant was named Hb Kalundborg after the place of origin of the proband. Heterozygosity for this mutation appears to have no clinical significance in itself except for a possibly slightly lower oxygen affinity. However, it interferes with Hb A1c measurement by HPLC, causing a falsely high Hb A1c concentration when using the G11 apparatus with clinical implications possibly to follow.

Keywords: Hb A1c; hemoglobin (Hb) variant; high performance liquid chromatography (HPLC); low-affinity Hb; β-Globin gene.

MeSH terms

  • Amino Acids
  • Chromatography, High Pressure Liquid / methods
  • Codon
  • Glycated Hemoglobin / analysis
  • Hemoglobinopathies* / diagnosis
  • Hemoglobinopathies* / genetics
  • Hemoglobins, Abnormal* / analysis
  • Humans
  • Mutation
  • Nucleotides
  • Oxygen
  • beta-Globins / chemistry

Substances

  • Amino Acids
  • Codon
  • Glycated Hemoglobin A
  • Hemoglobins, Abnormal
  • Nucleotides
  • beta-Globins
  • Oxygen