HbA mutation causing false‑normal HbA1c results determined by HPLC in a patient with type 2 diabetes mellitus: A case report

Wang,Juan; Wang,Yi; Lv,Wenshan; Yang,Lili; Huang,Meng; Wang,Qing

doi:10.3892/etm.2021.10277

August-2021 Volume 22 Issue 2

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August-2021 Volume 22 Issue 2

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Case Report Open Access

HbA mutation causing false‑normal HbA1c results determined by HPLC in a patient with type 2 diabetes mellitus: A case report

Authors:
- Juan Wang
- Yi Wang
- Wenshan Lv
- Lili Yang
- Meng Huang
- Qing Wang
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Affiliations: Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266061, P.R. China, Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266061, P.R. China

Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Article Number: 845
|
Published online on: June 7, 2021

https://doi.org/10.3892/etm.2021.10277
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Abstract

Glycated hemoglobin A1c (HbA1c) is a convenient measure of long‑term blood glucose concentrations and it is an accepted diagnostic test for type 2 diabetes mellitus (T2DM). The present study reported on a female patient with T2DM, whose fasting blood glucose and glycated albumin levels were elevated, while the HbA1c levels were in the normal range, which was inconsistent with the patient's clinical diagnosis. In the subsequent analysis, genomic DNA was extracted from the patient's blood and the HbA genes were analyzed by Sanger sequencing. The results indicated that the patient's HbA α1/2‑chain genes had no mutations, while two HbA β‑chain gene mutations were present, including an HBB:c.9T>C variant and a Hb G‑Coushatta variant. The HBB:c.9T>C variant is a silent mutation that has no effect on HbA1c levels when detected by ion‑exchange high‑performance liquid chromatography (HPLC), while the Hb G‑Coushatta variant may cause a discrepancy between blood glucose control and HbA1c levels when detected by ion‑exchange HPLC. These results suggested that the Hb G‑Coushatta variant gave rise to the false‑normal result regarding HbA1c levels when detected by ion‑exchange HPLC that was inconsistent with the clinical manifestations in this patient.

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1	International Expert Committee. International expert committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care. 32:1327–1334. 2009.PubMed/NCBI View Article : Google Scholar
2	Standards of medical care in diabetes-2016: Summary of revisions. Diabetes Care. 39 (Suppl 1):S4–S5. 2016.PubMed/NCBI View Article : Google Scholar
3	Gallagher EJ, Le Roith D and Bloomgarden Z: Review of hemoglobin A(1c) in the management of diabetes. J Diabetes. 1:9–17. 2009.PubMed/NCBI View Article : Google Scholar
4	Little RR, Rohlfing CL, Hanson S, Connolly S, Higgins T, Weykamp CW, D'Costa M, Luzzi V, Owen WE and Roberts WL: Effects of hemoglobin (Hb) E and HbD traits on measurements of glycated Hb (HbA1c) by 23 methods. Clin Chem. 54:1277–1282. 2008.PubMed/NCBI View Article : Google Scholar
5	Dessi M, Pieri M, Pignalosa S, Martino FG and Zenobi R: Performances of capillary electrophoresis and HPLC methods in HbA1c determination: Diagnostic accuracy in HbS and HbD-Iran variants' presence. J Clin Lab Anal. 29:57–60. 2015.PubMed/NCBI View Article : Google Scholar
6	Lorenzo-Medina M, De-La-Iglesia S, Ropero P, Nogueira-Salgueiro P and Santana-Benitez J: Effects of hemoglobin variants on hemoglobin a1c values measured using a high-performance liquid chromatography method. J Diabetes Sci Technol. 8:1168–1176. 2014.PubMed/NCBI View Article : Google Scholar
7	Al-Hakeim HK and Abdulzahra MS: Correlation between glycated hemoglobin and homa indices in type 2 diabetes mellitus: Prediction of beta-cell function from glycated hemoglobin. J Med Biochem. 34:191–199. 2015.PubMed/NCBI View Article : Google Scholar
8	Ogawa K, Bando T, Ogawa M, Miyazaki A, Nakanishi T and Shimizu A: Hemoglobin variant HbG-coushatta (beta-22 Glu->Ala) found by dissociation of blood glucose from values of HbA1C measured by HPLC. Intern Med. 42:781–787. 2003.PubMed/NCBI
9	Kurtoğlu AU, Eren E, Aslan V, Erkal Ö, Kurtoğlu E and Yilmaz N: Heterozygote hemoglobin G-coushatta as the cause of a falsely decreased hemoglobin A1C in an Ion-exchange HPLC method. J Med Biochem. 36:270–273. 2017.PubMed/NCBI View Article : Google Scholar
10	Rohlfing C, Hanson S, Weykamp C, Siebelder C, Higgins T, Molinaro R, Yip PM and Little RR: Effects of hemoglobin C, D, E and S traits on measurements of hemoglobin A1c by twelve methods. Clin Chim Acta. 455:80–83. 2016.PubMed/NCBI View Article : Google Scholar
11	Rodriguez-Segade S, Rodriguez J, Cabezas-Agricola JM, Casanueva FF and Camiña F: Progression of nephropathy in type 2 diabetes: The glycation gap is a significant predictor after adjustment for glycohemoglobin (Hb A1c). Clin Chem. 57:264–271. 2011.PubMed/NCBI View Article : Google Scholar
12	Schnedl WJ, Reisinger EC, Katzensteiner S, Lipp RW, Schreiber F, Hopmeier P and Krejs GJ: Haemoglobin O Padova and falsely low haemoglobin A1c in a patient with type I diabetes. J Clin Pathol. 50:434–435. 1997.PubMed/NCBI View Article : Google Scholar
13	Estey MP, Rodriguez-Capote K, Adelowokan T and Higgins T: Hemoglobin Hirose: A rare beta chain variant causing falsely low HbA1c by HPLC. Clin Biochem. 49:498–501. 2016.PubMed/NCBI View Article : Google Scholar
14	Xu A, Sun J, Li J, Chen W, Zheng R, Han Z and Ji L: Hb I: A alpha-globin chain variant causing unexpected HbA1c results. J Clin Lab Anal. 33(e22671)2019.PubMed/NCBI View Article : Google Scholar