Interference with hemoglobin A(1C) determination by the hemoglobin variant Shelby

Area of Science:

• Hematology
• Clinical Chemistry
• Genetics

Background:

• Hemoglobin A1c (HbA1c) is a key biomarker for diabetes management.
• Certain hemoglobin variants can interfere with standard HbA1c measurement methods, leading to inaccurate results.
• Ion-exchange high-performance liquid chromatography (HPLC) is a common method for HbA1c determination.

Observation:

• A 46-year-old African American man presented with a falsely elevated HbA1c detected by ion-exchange HPLC.
• Further analysis revealed an unknown hemoglobin variant peak (26.3% proportion) without mass shift in globin proteins.
• Peripheral blood smear showed increased target cells, despite a normal hemoglobin level.

Findings:

• DNA sequencing identified a missense mutation in the beta-globin gene, confirming the hemoglobin Shelby trait.
• Boronate-affinity HPLC, an alternative method, yielded an accurate HbA1c of 3.9%, aligning with normal blood glucose levels.
• The patient was asymptomatic, indicating the trait did not cause overt clinical symptoms.

Implications:

• This case underscores the necessity of recognizing and accounting for hemoglobin variants in HbA1c testing.
• Accurate HbA1c measurement is crucial for appropriate diabetes diagnosis and management.
• Utilizing alternative HbA1c methodologies can resolve discrepancies caused by hemoglobin variants.