Undetectable Glycated Haemoglobin Associated with Asymptomatic Sickle Cell Disease: A Case Report

Authors

  • Temilola O Owojuyigbe Obafemi Awolowo University, Ile-Ife https://orcid.org/0000-0003-3977-2326 (unauthenticated)
  • Abiodun K Ajeigbe Obafemi Awolowo University, Ile-Ife
  • Ronke A Makinde Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife
  • Tewogbade A Adedeji Obafemi Awolowo University, Ile-Ife

DOI:

https://doi.org/10.30442/ahr.1104-11-309

Keywords:

Diabetes mellitus, Glycated haemoglobin, Haemoglobinopathy, Sickle Cell Disease

Abstract

Glycated haemoglobin (HbA1c) testing is indicated for the screening and therapeutic monitoring of diabetes mellitus (DM). A 42-year-old woman was found to have undetectable glycated haemoglobin (HbA1c) with the Cobas C311® analyser during screening for diabetes mellitus. The fasting plasma glucose was normal. Haemoglobin (Hb) phenotyping by automated cellulose acetate electrophoresis revealed HbSC disease. The diagnosis of HbSC was confirmed by high-performance liquid chromatography (HPLC) and capillary electrophoresis. The presence of haemoglobinopathies can affect the results of HbA1c assays. In populations with a high prevalence of haemoglobinopathies, abnormally low or discordant HbA1c results should raise a suspicion of the presence of haemoglobinopathies. Alternative assay methodologies or biomarkers may be required for proper clinical management in such cases.

References

1. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2012;35:S64-S71. https://doi.org/10.2337/dc12-s064.

2. Chen Z, Shao L, Jiang M, Ba X, Ma B, Zhou T. Interpretation of HbA1c lies at the intersection of analytical methodology, clinical biochemistry and hematology (Review). Exp Ther Med 2022;24:707. https://doi.org/10.3892/etm.2022.11643.

3. Gupta M, Thalquotra M, Rao P. P3 fraction: Effect on HbA1c values by HPLC. J Clin Diagn Res. 2016;10:BC12-BC14. https://doi.org/10.7860/jcdr/2016/21092.8451.

4. Camargo JL, Gross JL. Conditions associated with very low values of glycohaemoglobin measured by an HPLC method. J Clin Pathol 2004;57:346-349. https://doi.org/10.1136/jcp.2002.007088.

5. Lorenzo-Medina M, De-La-Iglesia S, Ropero P, Nogueira-Salgueiro P, Santana-Benitez J. Effects of hemoglobin variants on hemoglobin A1c values measured using a high-performance liquid chromatography method. J Diabetes Sci Technol 2014;8:1168-1176. https://doi.org/10.1177/1932296814538774.

6. Bry L, Chen PC, Sacks DB. Effects of hemoglobin variants and chemically modified derivatives on assays for glycohemoglobin. Clin Chem 2001;47:153-163. https://doi.org/10.1093/clinchem/47.2.153.

7. Klonoff DC. Hemoglobinopathies and hemoglobin A1c in diabetes mellitus. J Diabetes Sci Technol. 2020;14:3-7. https://doi.org/10.1177/1932296819841698.

8. Adewoyin A, Busari O, Aworanti O. Hemoglobin phenotypes in Nigeria: Data from a national reference laboratory. Am J Clin Pathol 2019;152:S115-S116. https://doi.org/10.1093/ajcp/aqz121.027.

9. Pecker LH, Schaefer BA, Luchtman-Jones L. Knowledge insufficient: The management of haemoglobin SC disease. Br J Haematol 2017;176:515-526. https://doi.org/10.1111/bjh.14444.

10. Ameh SJ, Tarfa FD, Ebeshi BU. Traditional herbal management of sickle cell anemia: lessons from Nigeria. Anemia. 2012;2012:607436. https://doi.org/10.1155/2012/607436.

11. François L, Nadjib H, Katia Stankovic S, Virginie A, Gilles G, Robert G, et al. Hemoglobin SC disease complications: A clinical study of 179 cases. Haematologica 2012;97:1136-1141. https://doi.org/10.3324/haematol.2011.055202.

12. Poillon WN, Kim BC, Rodgers GP, Noguchi CT, Schechter AN. Sparing effect of hemoglobin F and hemoglobin A2 on the polymerisation of hemoglobin S at physiologic ligand saturations. Proc Natl Acad Sci U S A 1993;90(11):5039-5043. https://doi.org/10.1073/pnas.90.11.5039.

13. Sacks DB, Arnold M, Bakris GL, Bruns DE, Horvath AR, Kirkman MS, et al. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Diabetes Care. 2011;34:e61-e99. https://doi.org/10.2337/dc11-9998.

14. Aleyassine H. Glycosylation of hemoglobin S and hemoglobin C. Clin Chem. 1980;26:526-527. https://doi.org/10.1093/clinchem/26.3.526.

15. Sosenko JM, Flückiger R, Platt OS, Gabbay KH. Glycosylation of variant hemoglobins in normal and diabetic subjects. Diabetes Care 1980;3:590-593. https://doi.org/10.2337/diacare.3.5.590.

16. Lacy ME, Wellenius GA, Sumner AE, Correa A, Carnethon MR, Liem RI, et al. Association of sickle cell trait with hemoglobin A1c in African Americans. JAMA 2017;317:507-515. https://doi/org//10.1001/jama.2016.21035.

17. Wu WC, Lacy ME, Correa A, Carnethon M, Reiner AP, Eaton CB, et al. Association between hemoglobin A1c and glycemia in African Americans with and without sickle cell trait and Whites, results from CARDIA and the Jackson Heart Study. J Diabetes Treat 2018;3. https://doi.org/10.29011/2574-7568.000063.

18. Chang J, Hoke C, Ettinger B, Penerian G. Evaluation and interference study of hemoglobin A1c measured by turbidimetric inhibition immunoassay. Am J Clin Pathol 1998;109:274-278. https://doi.org/10.1093/ajcp/109.3.274.

19. Wu X, Chao Y, Wan Z, Wang Y, Ma Y, Ke P, et al. A comparative evaluation of the analytical performances of Capillarys 2 Flex Piercing, Tosoh HLC-723 G8, Premier Hb9210, and Roche Cobas c501 Tina-quant Gen 2 analysers for HbA(1c) determination. Biochem Med (Zagreb) 2016;26:353-364. https://doi.org/10.11613/bm.2016.039.

20. Bozimo G, Nkpozi MO, Ugwu A, Gomba VE, Abonyi CM, Unachukwu C. Glycated hemoglobin as a screening tool in the diagnosis of diabetes mellitus among adult patients in a tertiary health facility in Port Harcourt, Niger Delta region of Nigeria. APIK J Intern Med 2025;13:28-32. https://doi.org//10.4103/ajim.ajim_115_23.

Downloads

Published

2025-12-29

Issue

Vol. 11 No. 4 (2025)

Section

Case Report

License

Copyright (c) 2025 Annals of Health Research (The Journal of the Medical and Dental Consultants Association of Nigeria, OOUTH, Sagamu, Nigeria)

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

The articles and other materials published in the Annals of Health Research are protected by the Nigerian Copyright laws. The journal owns the copyright over every article, scientific and intellectual materials published in it. However, the journal grants all authors, users and researchers access to the materials published in the journal with the permission to copy, use and distribute the materials contained therein only for academic, scientific and non-commercial purposes.