A Rare Hemoglobin Variant Causing Misleading Measurements of Hemoglobin [A.sub.1c]

Glycated hemoglobin [A.sub.1c] ([HbA.sub.1c]) Is considered the standard of care for the testing and monitoring of diabetes. Its ability to accurately reflect glycemla, however, is imperfect. Hemoglobin variants--mutant forms of hemoglobin caused by genetic variation present in 7% of the population--are known to adversely affect the ability of [HbA.sub.1c] measurement to reflect glycemic control. We report an illustrative case of a 64-year-old nondiabetic man with a steadily decreasing [HbA.sub.1c] and no symptoms of hypoglycemia or concerning family history. Preliminary investigative workup returned nothing of significance. Genetic sequencing, however, identified a rare benign hemoglobin variant: a heterozygous missense mutation in the gene encoding the hemoglobin p chain (c.155C > A, p.Pro51His). This variant has been reported only once previously, and the report predates genetic sequence data of the variant. Although this variant had no clinical implications for the patient, it was the cause of falsely low [HbA.sub.1c] levels on high-performance ion-exchange chromatography. This case highlights the importance of considering the effect of hemoglobin variants on the measurement of [HbA.sub.1c]. When available, family history should be carefully considered. Clinicians should suspect hemoglobin variants when [HbA.sub.1c] is too high or low, or discordant with the clinical picture. Key Words: hemoglobin variant, hemoglobin [A.sub.1c] Abbreviations: HbA, adult hemoglobin; [HbA.sub.1c], glycated hemoglobin [A.sub.1c]; HPIEC, high-performance ion- exchange chromatography.