Spuriously elevated hemoglobin A1c in a diabetic patient with two rare hemoglobin variants (Hemoglobin Raleigh and Hemoglobin Russ)

We describe a patient with Type I diabetes mellitus whose hemoglobin A1c (HbA1c) level was markedly elevated (45.3%) when initially measured by routine low pressure ion exchange chromatography. Possible interference of a variant hemoglobin (Hb) was suspected, and subsequently the patient and his father were found to have two very rare Hb variants (Hb Raleigh and Hb Russ). Because of charge characteristics, Hb Raleigh cochromatographs with HbA1c, resulting in spuriously elevated assay values. Affinity chromatography of total glycosylated hemoglobin (GHb), a method that circumvents this interference, showed only slightly elevated GHb in the patient and a normal GHb in his nondiabetic father. This is the second family reported with both Hb Raleigh and Hb Russ and the fourth family where interference of Hb Raleigh with measurement of HbA1c resulted in detection of this Hb variant. More than 20 other Hb variants have been shown to interfere with estimation of HbA1c by ion exchange chromatography, the method most commonly employed in clinical laboratories. Clinicians should be aware of such potential interactions and request identification of variant Hb. Alternative methods of GHb measurement will allow reliable assessment of glycemic control in such patients.