Abstract
BACKGROUND: Hemoglobin A1c (HbA1c) is a critical biomarker used for the diagnosis and management of diabetes. However, nonglycemic genetic variations may affect the accuracy of HbA1c measurements. METHODS: We presented a clinical evaluation of a type 2 diabetic patient with an SLC4A1 (solute carrier family 4 member 1) gene mutation, characterized by high blood glucose and low HbA1c, and estimated the carrier frequency of SLC4A1 variants in Chinese population. RESULTS: A 56-year-old patient with type 2 diabetes presented with a low HbA1c level, an elevated glycated albumin percentage (GA), normal hemoglobin and albumin levels, hemolysis, and increased red blood cell osmotic fragility. Exome sequencing revealed a heterozygous mutation in SLC4A1 gene (c.1239_1241del), which is associated with hereditary spherocytosis. Further research indicates that around 0.756% of individuals in China carry pathogenic or likely pathogenic SLC4A1 variants. CONCLUSIONS: We report the SLC4A1 c.1239_1241del variant, which perturbs HbA1c via nonglycemic mechanisms, likely through a reduction in the erythrocyte lifespan, and similar variants may not be rare in Chinese population.