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

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.