Appearing in the Journal of Medical Cases, a case study outlines what is only the fourth reported case worldwide of a rare hemoglobin (Hb) variant, Hb South Florida (Hb-SF) that can cause falsely elevated HbA1c results during standard laboratory testing in the range of poorly controlled diabetes mellitus.

During routine lab work using the ion-exchange high performance liquid chromatography (HPLC) method, a 42-year-old female patient with a history of sclerosing bone dysplasia (treated with acetaminophen/codeine) was found to have an elevated HbA1c of 13.8%. The patient denied any family history of diabetes but repeat testing showed HbA1c of 12.8% with fasting blood sugar of 98mg/dL. Over the course of several months, her HbA1c was persistently elevated at 12–14% with mildly elevated blood sugar readings. Finally, Hb electrophoresis was performed at an endocrinology clinic and the results indicated that the patients was heterozygous for Hb-SF that leads to falsely elevated HbA1c levels. When evaluated by affinity column HPLC, her HbA1c levels were in the normoglycemic range. 

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While there are many commercially available tests for measuring HbA1c levels, ion-exchange HPLC separates Hb chains based on their charge differences. The Hb-SF variant substitutes a neutral amino acid for a charged one (valine for methionine), which decreases the transit time in the ion exchange column; this causes it to co-elute together with HbA1c and produce a falsely elevated value.

While this is only the fourth reported case of Hb-SF, this case study emphasizes the importance of the many Hb variants that could interfere with routine laboratory tests. The authors conclude that clinicians should consider multiple factors besides HbA1c in diabetes assessment and diagnosis, and that abnormal Hb variants could be driving increased HbA1c levels in patients who do not have symptoms consistent with diabetes and normal blood glucose levels.

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