Hemoglobin Wayne Variant Interfering with Hemoglobin A1C Measurement

Abstract

Objective:To describe the effect of hemoglobin Wayne variant on hemoglobin A1c (A1c) accuracy and to stress the importance of patient-physician communication and trust.Methods: We present the clinical history and laboratory findings of 2 patients, with a review of related literature.Results: Two older patients were diagnosed with diabetes mellitus (DM) and suffered from frequent hypoglycemia resulting from titrating their diabetes medications based on an extremely elevated A1c (>11% [97 mmol/ mol]) obtained through high-performance liquid chromatography. Discrepancies were noticed between their blood glucose logs and their A1c results. Ultimately, both were found to have heterogenous hemoglobin Wayne variant by hemoglobin electrophoresis. Repeat immunoassay found the A1c to be very low, in the 5 to 6.2% (31 to 44 mmol/ mol) range. One of the patients did not even meet diagnostic criteria for DM.Conclusion: A1c testing is susceptible to misinterpretation due to multiple interfering factors. Hemoglobin variants should be considered as a differential when there are discrepancies between A1c and blood glucose levels.Trust between the patient and the physician is essential in raising clinical suspicion and avoiding potentially lethal outcomes. (AACE Clinical Case Rep. 2019;5:e59-e61) Abbreviations: A1c = glycated hemoglobin; DM = diabetes mellitus; HPLC = high-performance liquid chromatography

Hemoglobin Wayne: A Rare Variant That Can Cause Falsely Elevated Hemoglobin A1c

“…testing [1]. Boronate affinity techniques utilize m-aminophenylboronic acid, which reacts selectively with the cis-diol groups of glucose coupled to Hgb.…”

“…Although hemoglobin A1c is commonly used to diagnose diabetes and monitor the effects of medications in individuals with diabetes, it can be troublesome in patients with hemoglobinopathies or disorders that affect red cell turnovers, such as hemolytic anemia, blood transfusions, or severe blood loss [ 1 ]. Reduced erythropoiesis can generate an erroneously elevated HbA1c (e.g.…”

“…Indeed, an increase in A1c indicates a 120-day increase in mean plasma glucose concentrations (the average erythrocyte lifespan). Some A1c assay methods are hampered by hemoglobinopathies, which affect red blood cell survival or hemoglobin glycation [ 1 ].…”

“…Single amino acid substitutions cause the majority of hemoglobin variants. Deamination of the hemoglobin Wayne protein occurs at asparagine 139, resulting in two hemoglobin Wayne molecules: hemoglobin Wayne I (asparagine as residue 139) and hemoglobin Wayne II (aspartic acid as residue 139) [ 1 ]. Most heterogeneous hemoglobinopathies are benign and clinically silent, and if not considered as the reason for falsely increased A1c, they can go unnoticed, leading to misdiagnosis of DM.…”

“…Diabetes mellitus (DM) can be diagnosed using two consecutive measures of glycated hemoglobin (A1c) ≥ 6.5% (48 mmol/mol), according to the World Health Organization and the American Diabetes Association [ 1 ]. It is well established that some hemoglobin (Hgb) variations can skew A1c results in a variety of ways [ 2 ].…”