Hemoglobin South Florida: New Variant With Normal Electrophoretic Pattern Mistaken for Glycosylated Hemoglobin

Abstract

An 8.75-yr-old Caucasian boy was discovered to have a markedly elevated (14.8%) hemoglobin A1c (HbA1c) as estimated by ion-exchange chromatography (Bio Rex 70). Glycohemoglobin (GHb) measured by a colorimetric method with thiobarbituric acid (TBA) was normal (equivalent to a 6.4% HbA1c). Nondiabetic quantities of GHb were found with affinity chromatography, and the glucose tolerance test was normal. Intensive efforts to identify an abnormal variant hemoglobin by several electrophoretic methods were unsuccessful. A family survey identified a similar abnormality in 11 other individuals, revealing an autosomal-dominant pattern. None of the affected individuals had any other hematologic abnormality. Structural analysis in one family member revealed a new hemoglobin variant (approximately 45% of the total hemoglobin) with the substitution of methionine for valine at the beta-NH2-terminal. In addition, the initiator methionine residue was preserved. Approximately 20% of the variant hemoglobin was modified by acetylation of the NH2-terminal methionine. The modified variant coeluted with HbA1c. We suggest that patients who do not have an explanation for their elevated HbA1c should have GHb measured by the TBA method or affinity chromatography because hemoglobin electrophoresis does not identify this confounding artifact.

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

“…He presented with symptoms of poor weight gain, polyuria, a normal glucose tolerance test, a normal Hb electrophoresis (cellulose acetate method) and HbA1c of 14.8% (ionexchange chromatography) [2,9]. Despite the normal electrophoresis results, there was a suspicion for an Hb variant due to elevated HbA1c levels in the absence of diabetes.…”

“…2015;6(5):229-231 electrophoresis was performed due to suspicion for a hemoglobinopathy. The results showed that the patient was heterozygous for a rare Hb variant called Hb-SF that causes falsely elevated HbA1c levels [2]. Her corrected HbA1c, when evaluated by affinity column HPLC showed results in the normoglycemic range ( Table 2).…”

“…They concluded that when this Hb variant is suspected the test should be repeated with affinity Ratajczak et al J Med Cases. 2015;6(5):229-231 column testing [2,9]. The variant Hb-SF has since been reported in two other cases worldwide, one case in Turkey in 2013 [10] and one in Malaysia in 2006 [11].…”

“…We report a fourth case of a rare hemoglobin (Hb) variant, Hb South Florida (Hb-SF) with only three cases reported previously worldwide to our knowledge since its initial description in 1985. It causes falsely elevated HbA1c results during standard laboratory testing in the range of poorly controlled diabetes mellitus [2].…”

Mass spectrometry based characterization of Hb Beckman variant in a falsely elevated HbA1c sample

“…Occasionally, genetic variants of hemoglobin, originated by the point mutation in the globin gene, coelute with HbA 1c , which leads to overestimation of the glycemic index and subsequently wrong diagnosis of diabetes mellitus [2]. Post-translational modifications, such as acetylation of a few hemoglobin variants, have also been reported to result in coelution with HbA 1c [4,5]. Examples include Hb Raleigh, Hb Graz, Hb South Florida, Hb Sherwood Forest, and Hb Niigata [2].…”