Hb I: A α-globin chain variant causing unexpected HbA1c results

Abstract

Background: HbA1c is the standard bio-marker for glycemic control in patients with diabetes. Here, we report a α-globin chain variant and evaluate its effect on HbA1c measurements. Methods: A 21-year-old female was suspected of harboring a hemoglobin variant following HbA1c measurement during a routine examination using Variant II Turbo 2.0 (Bio-Rad). An oral glucose tolerance test was performed using an AU5800 clinical chemistry system (Beckman Coulter). HbA1c was reanalyzed using D10 (Bio-Rad), Capillarys 2 Flex Piercing (Sebia), and Premier Hb9210 (Trinity Biotech). Hemoglobin analysis was performed using high-performance liquid chromatography (HPLC) on the Bio-Rad Variant II (β-thalassemia short program) and capillary electrophoresis (CE, Capillarys 2 Flex Piercing, Hb program). Sanger sequencing of α and β genes was also conducted. Results: HbA1c was initially measured at 24.2% using Variant II Turbo 2.0. For the oral glucose tolerance test, fasting glucose, 1-hour, and 2-hour levels were recorded as 4.25, 7.89, and 5.34 mmol/L, respectively. Subsequently, HbA1c values determined by D10, Capillarys 2 Flex Piercing (HbA1c program), and Premier Hb9210 were 4.5% (26 mmol/mol), no HbA1c value, and 4.8 (29 mmol/mol), respectively. Hemoglobin analyzed using CE and HPLC revealed an abnormal hemoglobin. Sanger sequencing identified a transversion mutation of the α2 gene [CD16(AAG>GAG), Lys>Glu, HBA2: c.49 A>G], corresponding to a Hb I variant. Conclusion: An unusually high HbA1c or discordance between blood sugar and HbA1c values should alert about the possibilities of hemoglobin variants.