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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter

IMPACT FACTOR 2018: 3.638

CiteScore 2018: 2.44

SCImago Journal Rank (SJR) 2018: 1.191
Source Normalized Impact per Paper (SNIP) 2018: 1.205

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Volume 46, Issue 6


The silent hemoglobin α chain variant Hb Riccarton [α51(CE9)Gly→Ser] may affect HbA1c determination on the HLC-723 G7 analyzer

Johannes M.W. van den Ouweland / Henny van Daal / Corné H. Klaassen / Yvonne van Aarssen / Cornelis L. Harteveld
  • 5Department of Human and Clinical Genetics, The Hemoglobinopathies Laboratory, Leiden University Medical Center, Leiden, The Netherlands
  • Other articles by this author:
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/ Piero C. Giordano
  • 6Department of Human and Clinical Genetics, The Hemoglobinopathies Laboratory, Leiden University Medical Center, Leiden, The Netherlands
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar


Background: Structural hemoglobin variants can affect the accuracy of hemoglobin A1c (HbA1c) testing and represent the most common pitfall in the determination of HbA1c. We here describe the characterization of an α chain variant in diabetic patients as the cause of an abnormal presentation of the HbA1c fraction on the HLC-723 G7 analyzer.

Methods: HbA1c analysis was performed using various HPLC-based HbA1c analyzers and by immunoassay. α-Globin mutation analysis was performed by GAP-PCR and DNA sequencing.

Results: The peak partially overlapping HbA1c in the chromatogram represents the glycated fraction of the silent α chain variant Hb Riccarton [α51(CE9)Gly→Ser]. This aberrant peak is uniquely identified by the HLC-723 instrument, as it is not observed on other HPLC-based HbA1c analyzers. Occasionally, the HLC-723 may fail to properly integrate both glycated Hb fractions, resulting in a falsely low HbA1c result. The variant was confirmed in samples from other diabetic patients with identical chromatographic patterns.

Conclusions: The silent α chain variant Hb Riccarton [α51(CE9)Gly→Ser] leads to an abnormal chromatographic presentation on the HLC-723 analyzer with a risk of erroneous HbA1c determination. Manual validation of chromatograms to detect abnormalities caused by Hb variants is important to prevent incorrectly produced HbA1c results from being reported.

Clin Chem Lab Med 2008;46:827–30.

Keywords: α-thalassemia; diabetes mellitus; glycated hemoglobin; hemoglobin A1c; hemoglobin variants; ion exchange HPLC

About the article

Corresponding author: J.M.W. van den Ouweland, Department of Clinical Chemistry, Canisius-Wilhelmina Hospital, Weg door Jonkerbos 100, 6500 Nijmegen, The Netherlands Phone: +31-24-3658680, Fax: +31-24-3658671,

Received: 2007-11-20

Accepted: 2008-02-22

Published in Print: 2008-06-01

Citation Information: Clinical Chemistry and Laboratory Medicine, Volume 46, Issue 6, Pages 827–830, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2008.169.

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