First report of a rare hemoglobin variant in the Chinese population: clinical and hematological characteristics of Hb Norton [HBA2:c.217C>G] and its impact on HbA1c testing: a case report

Objectives Hemoglobin (Hb) variants are a common type of single-gene disorder and a frequent source of interference in HbA1c testing. Here, we first report a rare Hb variant, Hb Norton [HBA2:c.217C>G], in the Chinese population.Methods and results A 38-year-old man presented with a normal clinical and hematological phenotype. He was suspected of carrying an Hb variant following an HbA1c measurement using a high-performance liquid chromatography (HPLC) method (Bio-Rad D100), which resulted in an extremely high value of 20.24%. HbA1c was reanalyzed using a capillary electrophoresis (CE) method (Capillarys3 TERA) and a boronate affinity HPLC system (Premier Hb9210), and the results were 5.49% and 5.60%, respectively. Hemoglobin analysis by CE and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) revealed a variant peak with a mass-to-charge ratio (m/z) = 10105 Da. Sanger sequencing confirmed the presence of a rare Hb variant, Hb Norton [HBA2:c.217C>G]. It was conclusively confirmed that the co-elution of Hb Norton and HbA1c components led to the falsely elevated HbA1c values.Conclusions Some rare variants can severely affect HbA1c analysis. When encountering abnormally high values that are difficult to explain, one should consider whether variant interference is present.