Fourth Reported Case of Hemoglobin South Florida: A Rare Hemoglobin Variant That Causes Falsely Elevated HbA1c Values

Theresa Ratajczak, Sadia Afaz, Ankur Gupta


We report a case of a rare hemoglobin (Hb) variant, Hb South Florida (Hb-SF) with only three cases reported worldwide to our knowledge since initial description in 1985. It causes falsely elevated glycosylated hemoglobin (HbA1c) results during standard laboratory testing in the range of poorly controlled diabetes mellitus. A 42-year-old woman with a history of sclerosing bone dysplasia was noted to have an elevated HbA1c (13.8%) during routine blood work using the ion-exchange high performance liquid chromatography (HPLC) method. The patient did not have a prior diagnosis of diabetes mellitus and denied any symptoms consistent with diabetes. Physical exam was unremarkable. Her blood sugars were normal to minimally elevated. Over several months, she was noted to have persistent elevation in HbA1c in the range of 12-14%. She remained asymptomatic. The patient was referred to endocrinology clinic. Hb electrophoresis was performed due to suspicion for a hemoglobinopathy. The patient was noted to be heterozygous for a rare Hb variant called Hb South Florida that causes falsely elevated HbA1c levels. Her corrected HbA1c, when evaluated by affinity column HPLC, was in normoglycemic range. Hb South Florida was first described in 1985 in Tampa Florida and has since been reported in two other cases worldwide. The Hb is not associated with any clinical disorder reported in literature. There are many commercially available tests for measuring HbA1c levels. Additionally, structural variants in Hb interfere with many of the methods. Ion-exchange HPLC separates Hb based on their charge differences. Hb South Florida variant substitutes a neutral amino acid for a charged one, with valine substituted by methionine. This alteration decreases the transit time in the ion exchange column and causes it to co-elute together with HbA1c, giving a falsely elevated value as they get measured as same species. Affinity chromatography is based on affinity of a species for a particular ligand. It recognizes the structure of the N-terminal glycated amino acids of the beta chain of Hb. In the case of Hb South Florida, it was able to separate the variant Hb from glycated species. This is the fourth case of Hb variant South Florida to our knowledge. It is important for clinicians to keep a wide perspective when making an assessment of diabetes solely based on HbA1c values. Patients who do not present with symptoms consistent with diabetes, and have normal blood glucose should prompt a further workup for abnormal Hb variants. This should be done in order to prevent incorrect diagnosis and treatment.

J Med Cases. 2015;6(5):229-231


Hemoglobinopathy; South Florida; Diabetes mellitus

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