Detection of hemoglobin variant HbS on the basis of discrepant HbA1c values in different measurement methods

Glycated hemoglobin (HbA1c) is commonly used to assess long-term glycemic control in patients with diabetes mellitus. Numerous conditions, including hemoglobinopathies, can alter HbA1c measurements and cause misleading results. More than 20 methods for determining HbA1c are commercially available to clinical laboratories. Herein, we report a diabetic patient in whom the HbS variant was detected on the basis of discrepant Hb1Ac levels estimated using immunonephelometry or high-performance liquid chromatography (HPLC). The patient, a 48-year-old African man with a 10-year history of type 2 diabetes, was referred to our hospital with an HbA1c level estimated at 13.3 % by immunonephelometry and 7.6 % by HPLC, whereas the glycoalbumin level was 47.5 %. These discrepancies prompted us to carry out genetic sequence analysis in which we identified an A → T transversion in codon 6 of the patient's HBB gene, corresponding to a predicted E6V substitution (βCD6) characteristic of HbS. Our results indicate that redundant measurements of HbA1c using diverse methods may be useful when the presence of abnormal Hb is suspected.