Hb Aalesund (HBA2: c.400_406delAGCACCG), an Unstable α-Globin Variant Found in a Norwegian Patient Causing Moderate Hemolytic Anemia and Falsely High Hb A1c Using Ion Exchange High Performance Liquid Chromatography

Runa M Grimholt; Bente Fjeld; Hilde Selsås; Lutz Schwettmann; Olav Klingenberg

doi:10.1080/03630269.2019.1614048

Hb Aalesund (HBA2: c.400_406delAGCACCG), an Unstable α-Globin Variant Found in a Norwegian Patient Causing Moderate Hemolytic Anemia and Falsely High Hb A_1c Using Ion Exchange High Performance Liquid Chromatography

Hemoglobin. 2019 Mar;43(2):122-125. doi: 10.1080/03630269.2019.1614048. Epub 2019 May 30.

Authors

Runa M Grimholt^{1

2

3}, Bente Fjeld^{1

2}, Hilde Selsås⁴, Lutz Schwettmann^{5

6}, Olav Klingenberg^{1

2}

Affiliations

¹ a Department of Medical Biochemistry , Oslo University Hospital, Ullevaal , Oslo , Norway.
² b Institute of Clinical Medicine , University of Oslo , Oslo , Norway.
³ c Department of Life Sciences and Health , OsloMet (Oslo Metropolitan) University , Oslo , Norway.
⁴ d Department of Endocrinology , Aalesund Hospital , Aalesund , Norway.
⁵ e Department of Medical Biochemistry , Aalesund Hospital , Aalesund , Norway.
⁶ f Department of Biological Sciences , Norwegian University of Science and Technology , Aalesund , Norway.

PMID: 31145010
DOI: 10.1080/03630269.2019.1614048

Abstract

A new unstable hemoglobin (Hb) variant, named Hb Aalesund, was detected during Hb A_1c measurement in a patient with a nearly compensated hemolytic anemia. Sequencing of the α-globin genes revealed a 7 bp deletion in exon 3 of the HBA2 gene (HBA2: c.400_406delAGCACCG) (NM_000517.4) causing a frameshift and a premature termination codon (PTC) two positions downstream. Apparently, the transcript bypassed nonsense-mediated decay (NMD), and a truncated protein was translated. The unstable Hb variant presumably underwent rapid denaturation, as heterozygosity of Hb Aalesund was associated with mild hemolytic anemia. In addition, the Hb variant interfered with Hb A_1c measurement by cation exchange high performance liquid chromatography (HPLC), causing a falsely high Hb A_1c result when using the Bio-Rad D10™ Hemoglobin Analyzer fast Hb A_1c Program.

Keywords: Hb A; hemoglobinopathy; hemolytic anemia; unstable hemoglobin (Hb); α-Globin gene.

Publication types

Case Reports

MeSH terms

Anemia, Hemolytic / genetics*
Chromatography, High Pressure Liquid / methods
Codon, Nonsense / genetics
Genetic Variation*
Glycated Hemoglobin / analysis*
Hemoglobins, Abnormal / genetics*
Heterozygote
Humans
Norway
Protein Stability
Sequence Analysis, DNA
Sequence Deletion / genetics
alpha-Globins / genetics*

Substances

Codon, Nonsense
Glycated Hemoglobin A
Hb Aalesund
Hemoglobins, Abnormal
alpha-Globins