A Hemoglobinopathy That Produces an Array of Different Hemoglobin A1c Values.

Area of Science:

• Clinical Chemistry
• Hematology
• Genetics

Background:

• Hemoglobin A1c (HbA1c) is a key biomarker for diabetes mellitus diagnosis, reflecting average blood glucose over ~3 months.
• Ion-exchange chromatography is a common method for HbA1c determination, capable of detecting common hemoglobin variants.
• Certain hemoglobinopathies can lower HbA1c by reducing red blood cell lifespan, while others can interfere with measurement.

Observation:

• A normoglycemic individual presented with significantly elevated HbA1c levels.
• The elevated HbA1c was initially measured using standard laboratory methods.
• Multiple testing methods, including immunoassay and capillary electrophoresis, were employed for verification.

Findings:

• A rare hemoglobinopathy, Hb Wayne (a frameshift mutation in the alpha globin gene), was identified as the cause of artifactual HbA1c elevation.
• Hb Wayne leads to an extended alpha globin polypeptide, forming Hb Wayne I and II variants.
• Alternative ion-exchange systems flagged the result as unreportable due to interference from Hb Wayne.

Implications:

• Artifactual HbA1c elevation can lead to misdiagnosis of diabetes mellitus and unnecessary treatment.
• Method comparison and awareness of hemoglobinopathies are crucial for accurate clinical interpretation of HbA1c results.
• Hb Wayne is a clinically silent disorder with no hematologic consequences, but significant implications for diagnostic testing.