Case Report: Rare Hemoglobin Variant Causes Elevated A1c, False Diagnosis of Pre-gestational Diabetes in Pregnancy [33H

Abstract

INTRODUCTION: Hemoglobin variants result from missense mutations that lead to substitution of amino acids within globin proteins, altering the structure of the hemoglobin molecule. Hemoglobin A1c (HbA1c) is commonly used to diagnosis and assess control of diabetes mellitus and can be falsely affected by hemoglobinopathies, hyperbilirubinemia, and hypertriglyceridemia. METHODS: We present a case of an obese Caucasian 27 year-old Gravid 3 Para 0020 with early HbA1c of 10.0 percent at 9-weeks gestation. The patient was diagnosed with pre-gestational diabetes, and referred for nutrition counseling with initiation of four times daily home blood sugar monitoring notable for consistently normal fasting and postprandial values. Due to continued discordant results in HbA1c level with her glucometer log and random glucose testing, hemoglobin electrophoresis was performed at 22-weeks gestation with findings suggestive of Hemoglobin Wayne, a rare hemoglobin variant that is clinically silent. Hemoglobin Wayne results from a frameshift mutation within the alpha chain resulting in a net charge that is similar to HbA1c. This common charge manifests as similar retention times on cation-exchange high-performance liquid chromatography, leading to an overestimation of HbA1c concentration. Genetic sequencing was pursued and the patient completed appropriately timed routine screening for gestational diabetes with normal results. CONCLUSION: Our case, the first reported in a pregnant patient, should remind clinicians of the few conditions that can lead to misrepresentation of HbA1c levels. Remaining vigilant in clarifying such an atypical patient presentation will decrease the risk of mismanaging, particularly over-treating, patients believed to be high-risk for diabetes.