Hidden in plain sight: Hb K Ibadan interference in HbA1c measurement across HPLC systems

Hemoglobin variants are a well-recognized cause of analytical interference in glycated hemoglobin (HbA1c) measurement and may lead to misclassification of glycemic status. We report a case of a patient with multiple comorbidities, including Myelodysplastic Syndrome (MDS), in whom routine HbA1c estimation showed discordant result in the High-Performance Liquid Chromatography (HPLC) platforms. An unknown peak eluting close to the HbA0 window was detected on the Bio-Rad D-10 system operating in HbA1c mode. However, no evidence of hemoglobin variants was observed when the same sample was analyzed in the dual (HbA₂/F) mode. In contrast, no abnormal peaks were detected on the Tosoh HLC-723GX platform during comparative analysis. Subsequent genetic analysis confirmed a heterozygous Hb K Ibadan mutation. Although Hb K Ibadan has previously been associated with falsely elevated HbA1c values, this patient demonstrated spuriously low HbA1c results. This case highlights that hemoglobin variants eluting near the HbA0 window may not always be apparent during routine hemoglobin variant analysis and can therefore remain unrecognized. Careful review of chromatograms during HbA1c testing, may provide important clues to the presence of such variants. Furthermore, variants considered rare may, in fact, be under-recognized due to reliance on chromatographic screening alone and the absence of systematic genetic follow-up.