Falsely high HbA1c value due to a novel α1-globin gene mutation: Hb shantou [α127(H10)Lys > Glu; HBA1: c.382 A > G

Abstract

Hemoglobin A1c (HbA1c) is a widely utilized biomarker for the diagnosis and management of diabetes mellitus. Here, we describe an α1-globin chain hemoglobin variant and investigate its effect on HbA1c measurement. A 26-year-old pregnant woman was suspected to harbor a hemoglobin variant following HbA1c measurement during a routine prenatal examination using D10 (Bio-Rad). An oral glucose tolerance test (OGTT) was performed using an AU5800 clinical chemistry system (Beckman Coulter). HbA1c was reanalyzed using VII-T 2.0 (Bio-Rad), Capillarys 2 Flex Piercing (C2FP, HbA1c program, Sebia), Premier Hb9210 (Trinity Biotech), and Cobas c501 (Cobas Tina-quant Hemoglobin A1c Gen.3). Glycated albumin (GA) level was also quantified using an enzymic method GA Kit (Lucica GA-L, Japan). Hemoglobin analysis was performed using high performance liquid chromatography on the Bio-Rad Variant II (β-thalassemia short program) and capillary electrophoresis (Capillarys 2 Flex Piercing, Hb program). Sanger sequencing of α and β genes was also conducted. HbA1c was initially measured at 16.0% (151 mmol/mol) using the D10 (Bio-Rad). Her OGTT result was normal. Subsequently, HbA1c values determined by VII-T 2.0, C2FP, Premier Hb9210, and Cobas c501 were 4.8% (29 mmol/mol), 4.9% (30 mmol/mol), 4.6% (27 mmol/mol), and 4.8% (29 mmol/mol), respectively. The glycated albumin level was 12.3% (reference: 10.8 ∼ 17.1%). Hemoglobin analyzed using CE and HPLC revealed an abnormal hemoglobin. By Sanger sequencing, we identified a transition mutation in the α1 gene Hb Shantou [α127(H10)Lys > Glu; HBA1: c.382 A > G]. Clinically silent variants may interfere with HbA1c determination by common methods.