[Difficulties caused by hemoglobin variants in the assessment of hemoglobin A1c regarding two cases].

In hemoglobinopathies, hemoglobin A1c measurement may be distorted, making accurate monitoring of diabetes difficult. In addition to clinically apparent forms, "silent" hemoglobin variants also occur; these do not affect the blood count and may remain undetectable with routine methods such as high-performance liquid chromatography or hemoglobin electrophoresis. We examined blood samples from two patients using high-performance liquid chromatography and a chemical immunoturbidimetric method for hemoglobin A1c, as well as hemoglobin electrophoresis and beta-globin gene sequencing. In both cases, repeated oral glucose tolerance testing consistently excluded diabetes mellitus. In the first patient, hemoglobin A1c measured by liquid chromatography was not evaluable because of an abnormal chromatogram, necessitating an alternative method. In the second patient, the high hemoglobin A1c value obtained by the chromatography method contradicted the clinical findings. After consultation between clinicians and the laboratory, electrophoresis and chemical hemoglobin A1c measurement were performed; neither case showed abnormal fractions via electrophoresis. In the first patient, the chemical method produced a measurable but unusually low hemoglobin A1c value. Genetic testing identified the hemoglobin Graz mutation, known to cause falsely high or undetectable hemoglobin A1c by chromatography and falsely low values by immunoassay, without clinical symptoms. In the second patient, the chemically measured hemoglobin A1c was lower yet remained in the prediabetic range; genetic analysis identified the hemoglobin Rainier variant, associated with erythrocytosis and likely responsible for falsely elevated hemoglobin A1c by both measurement techniques. These hemoglobin variants have not previously been described in Hungarian publications. These cases highlight the importance of alternative A1c measurement techniques, genetic testing and additional glucose metabolism markers such as fructosamine, as well as close cooperation between clinicians and laboratories. Orv Hetil. 2026; 167(5): 196-203.