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

Hemoglobin A(1c) (HbA(1c)) is a widely utilized biomarker for the diagnosis and management of diabetes mellitus. Here, we describe an alpha 1-globin chain hemoglobin variant and investigate its effect on HbA(1c) measurement. A 26-year-old pregnant woman was suspected to harbor a hemoglobin variant following HbA(1c) 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). HbA(1c) was reanalyzed using VII-T 2.0 (Bio-Rad), Capillarys 2 Flex Piercing (C2FP, HbA(1c) program, Sebia), Premier Hb9210 (Trinity Biotech), and Cobas c501 (Cobas Tina-quant Hemoglobin A(1c) 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 (beta-thalassemia short program) and capillary electrophoresis (Capillarys 2 Flex Piercing, Hb program). Sanger sequencing of alpha and beta genes was also conducted. HbA(1c) was initially measured at 16.0% (151 mmol/mol) using the D10 (Bio-Rad). Her OGTT result was normal. Subsequently, HbA(1c) 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 similar to 17.1%). Hemoglobin analyzed using CE and HPLC revealed an abnormal hemoglobin. By Sanger sequencing, we identified a transition mutation in the alpha 1 gene Hb Shantou [alpha 127(H10)Lys > Glu; HBA1: c.382 A > G]. Clinically silent variants may interfere with HbA(1c) determination by common methods.