We thank Li et al. (1) for their interest in our case report (2), which emphasized the value of visual inspection of chromatograms in clinical practice to assist interpretation of HbA1c.
For consistency and comparability with the first and only available report, by Wajcman et al. in 1992 (3), we presented the identified mutation as c.242T>A, p.Leu81His (rs33936967), without including the translational initiation codon in variant sequence numbering. According to the latest nomenclature recommendations of the Human Genome Variation Society in 2007 (4), starting with number 1 at the A of the ATG for nucleotides and at the methionine encoded by the translational initiation codon for protein-level amino acids, this variant is named c.245T>A, p.Leu82His, but not c.245T>A, p.Leu81His.
We agree with Li et al. (1) that different assays and different kits of the same assay for HbA1c measurement could have diverse interferences from different hemoglobin variants, as summarized by NGSP (5). However, the interference from rare hemoglobin variants should not be the sole criterion used to evaluate the clinical value of an assay or a kit, and the comparison of different measurement methods is beyond the scope of our case report. In the presence of rare variants, such as the Hb La Roche-sur-Yon variant in our reported patient, the HbA1c assay interference is hardly predictable and a case-by-case interpretation of the results is necessary. If the measured HbA1c level in our case had not been beyond the commonly observed range in clinical practice, this variant and the consequent interference would likely have been neglected. This fact raised our concern about the identification of cases with milder interference, and we thereby demonstrated the effectiveness and feasibility of visual inspection of the chromatogram for identifying some potential interferences. Nevertheless, it should be clarified that normal chromatograms do not guarantee the accuracy of HbA1c measurements, while abnormal chromatograms indicate the possibility of interference with measurements, under which circumstances a repeat measurement using a different assay is warranted.
In summary, the diagnostic process of our case suggested the value of visual inspection of high-performance liquid chromatography chromatograms to help identify inaccurate HbA1c measurements that were interfered with by hemoglobin variants, with no additional cost. However, our case provided little evidence regarding the selection of an assay or kit for HbA1c measurement.
Article Information
Funding. This letter received no specific funding from any bodies in the public, commercial, or not-for-profit sectors. S.L. was supported by grants from the National Natural Science Foundation of China (grant numbers 81400811 and 21534008), the National Basic Research Program of China (grant number 2015CB942800), the Scientific Research Project of Health and Family Planning Commission of Sichuan Province (grant numbers 130029, 150149, 17PJ063, and 17PJ445), the Cholesterol Fund by China Cardiovascular Foundation and China Heart House, and the International Visiting Program for Excellent Young Scholars of Sichuan University.
Duality of Interest. No potential conflicts of interest relevant to this article were reported.
