Two novel haemoglobin variants that affect haemoglobin A1c measurement by ion-exchange chromatography.

Abstract:

BACKGROUND:Haemoglobin (Hb) variants are well-known factors interfering with accurate HbA1c testing. This report describes two novel Hb variants leading to inappropriate quantification of HbA1c by ion-exchange chromatography. METHODS:Glycated forms of novel Hb variants were recognised in the blood of two patients with diabetes mellitus screened by HbA1c ion-exchange chromatography. Dedicated high-resolution cation-exchange chromatography and subsequent DNA sequencing revealed the exact nature of the variants. Other common techniques for quantifying HbA1c were applied on both samples and haematological parameters were determined to judge possible pathology associated with the novel Hb variants. RESULTS:A fraction of 15% of abnormal Hb was observed in a 37-year-old female. DNA sequencing revealed a heterozygous mutation in the α1-globin gene, resulting in a leucine-to-phenylalanine amino-acid substitution (HBA1: c.301C>T, p.Leu101Phe). We named this variant Hb Weesp. The other novel variant, Hb Haelen, presented as a 40% fraction in a 63-year-old male and resulted from a heterozygous amino acid substitution in the β-globin gene (HBB: c.335T>C, p.Val112Gly). The presence of both Hb variants resulted in aberrant separation of the Hb components, leading to an inadequate quantification of HbA1c. CONCLUSIONS:Close examination of HbA1c chromatograms revealed two novel, clinically silent Hb variants that interfere with HbA1c quantification. Healthcare providers need to be aware of the potential of such Hb variants when interpreting HbA1c results.

journal_name

Clin Chem Lab Med

authors

Bots M,Stroobants AK,Delzenne B,Soeters MR,de Vries JE,Weykamp CW,Norg RJ,Veldthuis M,Zwieten Rv

doi

10.1515/cclm-2015-0054

subject

Has Abstract

pub_date

2015-08-01 00:00:00

pages

1465-71

issue

9

eissn

1434-6621

issn

1437-4331

pii

/j/cclm.ahead-of-print/cclm-2015-0054/cclm-2015-00

journal_volume

53

pub_type

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