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

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 (ß-thalassemia short program) and capillary electrophoresis (CE, Capillarys 2 Flex Piercing, Hb program). Sanger sequencing of α and ß 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.

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

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 (ß-thalassemia short program) and capillary electrophoresis (Capillarys 2 Flex Piercing, Hb program). Sanger sequencing of α and ß 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.

A Novel ß-Globin Gene Mutation: Hb Shenzhen [ß90(F6)Glu→Ala, HBB: c.272A>C].

We report a novel ß-globin chain variant, Hb Shenzhen [ß90(F6)Glu→Ala, HBB: c.272A>C], in a 52-year-old Chinese individual. The hemoglobin (Hb) variant takes the position of the Hb D zone using capillary electrophoresis. Sanger sequencing revealed a novel base mutation on the ß-globin gene, HBB: c.272A>C, that resulted in a transition of glutamic acid to alanine at exon 2 of the ß-globin gene. We named this novel variant Hb Shenzhen for the geographic origin of this proband.

Hb Sichuan [α67(E16)Thr→Ile, HBA2: c.203C>T]: A Novel Hemoglobin Variant That Can Be Detected by Glycated Hemoglobin Electrophoresis.

We report a novel α2-globin chain hemoglobin (Hb) variant in a 23-year-old female of Chinese Han nationality. The Hb variant can be detected by glycated Hb electrophoresis (CapillaryS2, Hb A1c program). However, Hb fractions analyzed by capillary electrophoresis (CE) (CapillaryS2, Hb program) and high performance liquid chromatography (HPLC), (VARIANT II™ ß-Thalassemia Short Program) showed no suspicious Hb variant. Sanger sequencing revealed a novel mutation [α67(E16)Thr→Ile, HBA2: c.203C>T]. We named this novel variant Hb Sichuan after the geographic origin of the proband.