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Method-dependent HbA1c values in a family with hemoglobin Himeji
Eijun Nishihara1, Masafumi Koga, Seizo Kadowaki
1Kuma Hospital, Japan.
Summary
Hemoglobin Himeji, a variant hemoglobin, causes inaccurate HbA1c measurements across various methods due to increased glycation and altered properties. This highlights challenges in diabetes monitoring for individuals with this variant.
Area of Science:
- Clinical Chemistry
- Hematology
- Genetics
Background:
- Hb Himeji is a variant hemoglobin characterized by increased glycation in its mutated beta chain.
- This study investigated HbA1c measurement discrepancies in a family with Hb Himeji.
Observation:
- A proband with Hb Himeji showed elevated HbA1c (11.6%) by enzymatic assay despite normal oral glucose tolerance.
- Hemoglobin gene analysis confirmed Hb Himeji, a mutation at β140 (H18) Ala→Asp.
Findings:
- Significant method-dependent discrepancies in HbA1c values were observed across HPLC, immunoassay, enzymatic assay, affinity, and mass spectrometry methods.
- Glycation product measurements also varied by HPLC method (9.1% vs. 4.5%).
- Similar discrepancies were noted in other family members, including the proband's father with type 2 diabetes.
Implications:
- The findings underscore the challenges in accurate diabetes management for individuals with Hb Himeji.
- Differences in HPLC mobility, increased glycation, and antigenic changes of the variant beta chain contribute to measurement variability.
- Standard HbA1c assays may not be reliable for diagnosing or monitoring diabetes in patients with Hb Himeji.