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

Author:

Shah S C1,Malone J I1,Boissel J -P2,Kasper T J2

Affiliation:

1. University of South Florida Diabetes Center Tampa, Florida

2. Laboratory of the Howard Hughes Medical Institute, Hematology Division, Brigham and Women's Hospital, Harvard Medical School Boston, Massachusetts

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 (∼45% of the total hemoglobin) with the substitution of methionine for valine at the β-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.

Publisher

American Diabetes Association

Subject

Endocrinology, Diabetes and Metabolism,Internal Medicine

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