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Clinical Chemistry 49: 1412-1415, 2003; 10.1373/49.8.1412
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(Clinical Chemistry. 2003;49:1412-1415.)
© 2003 American Association for Clinical Chemistry, Inc.


Technical Briefs

Novel Hemoglobin Variant [ß66(E10) Lys->Asn], with Decreased Oxygen Affinity, Causes Falsely Low Hemoglobin A1c Values by HPLC

Ulrich Friess1,a, Alexander Beck1, Elisabeth Kohne2, Rainer Lehmann1, Sylvia Koch3, Hans-Ulrich Haring1, Reinhold-Michael Schmuelling1 and Erwin Schleicher1

1 Department of Medicine IV (Endocrinology, Metabolism, and Clinical Chemistry) and

3 Department of Medicine II (Hematology), University of Tuebingen, Otfried-Mueller-Strasse 10, D-72076 Tuebingen, Germany

2 Department of Pediatrics, Hemoglobin Facility, University of Ulm, Prittwitzstrasse 43, D-89075 Ulm, Germany

aauthor for correspondence: fax 49-7071-295974, e-mail ulrich.friess@med.uni-tuebingen.de

The first 20% of the full text of this article appears below.

The lysine in position 66 of the ß chain of hemoglobin (Hb) is located within the heme-binding pocket and is functionally important for oxygen binding (1). The lysine is exceptionally prone to glycation (2) and to modification by advanced glycation endproducts. In this journal, Iwamoto et al. (3) recently proposed an automated immunologic assay for Hb that is specifically advanced glycation endproduct-modified at Lys66.

Here we report on a novel Hb variant at this position [ß66(E10) Lys->Asn] found in a 73-year-old Caucasian patient with a 9-month history of type 1 diabetes mellitus secondary to recurrent necrotizing pancreatitis and choledocholithiasis. He was referred to us because of insufficient metabolic control: in the previous 4-month period, his fasting blood glucose (FBG) had been in the range of 6.3–13.6 mmol/L and his postprandial blood glucose had been in the range of 8.8–17.0 mmol/L. On admission, his FBG was 13.6 mmol/L. The blood smear results, complete blood count, reticulocyte count, and other markers for chronic anemia or hemolysis were within the appropriate reference intervals. HbF (0.6%) and HbA2 (2.1%) were not increased.

The initial measurement of HbA1c by cation-exchange HPLC (Tosoh HLC723-GHb A1c Version 2.2; Tosoh/Eurogenetics) gave a markedly low HbA1c value of 6.0% compared with 9.0% measured by the Bayer DCA immunologic method (Bayer Diagnostics). The chromatogram (Fig. 1A ) obtained with the routinely used 3-min HPLC program showed an abnormal peak interfering with the HbA1c fraction but no other major peak suspicious for a heterozygous Hb variant. Under optimized insulin treatment, the patient remained moderately hyperglycemic. Despite the patient’s persistent mild hyperglycemia, in subsequent HbA1c determinations under 3 and 6 months of optimized insulin treatment, the HPLC method consistently gave unexpectedly low . . . [Full Text of this Article]




The following articles in journals at HighWire Press have cited this article:


Home page
Clin. Chem.Home page
D. B. Sacks
Hemoglobin Variants and Hemoglobin A1c Analysis: Problem Solved?
Clin. Chem., August 1, 2003; 49(8): 1245 - 1247.
[Full Text] [PDF]




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