Specialist Biochemistry, Canterbury Health Laboratories, PO Box 151, Christchurch 8140, New Zealand.
Specialist Biochemistry, Canterbury Health Laboratories, PO Box 151, Christchurch 8140, New Zealand; Department of Pathology, University of Otago, PO Box 4345, Christchurch 8140, New Zealand.
Clin Biochem. 2022 Sep;107:62-66. doi: 10.1016/j.clinbiochem.2022.05.003. Epub 2022 May 14.
To describe a novel β-globin variant that interferes with HbA1c analysis by cation exchange HPLC.
Diabetes screening by HbA1c measurement was assessed using cation exchange HPLC and an immunoassay point-of-care analyzer. Routine hemoglobinopathy screening was performed including CBC, HbF and HbA measurement by cation exchange HPLC and capillary electrophoresis (CE). Further variant characterization was undertaken by ESI TOF mass spectrometry and DNA sequencing.
Discordant HbA1c results were obtained for our subject, with elevated HbA1c of 52 mmol/mol measured by cation exchange HPLC and a normal level of 34 mmol/mol by immunoassay. Abnormal HbA1c peak shape prompted hemoglobinopathy screening to investigate potential variant interference. Cation exchange HPLC (using β-thalassemia program) and CE results were apparently normal, with HbF and HbA detected within reference intervals. ESI TOF mass spectrometry revealed the presence of a variant β-globin chain. A novel missense variant was confirmed at codon 121 of the β-globin gene [β121 (GH4) Glu>Asp; HBB: c.366A>C], which we have named Hb Westport.
Hb Westport is a novel β-globin variant that interferes with HbA1c measurement by Bio-Rad D-100 cation exchange HPLC, giving a falsely elevated result. This was clinically significant for our subject because the erroneously elevated HbA1c value was above the diabetes diagnostic threshold. Alternative methods for diabetes assessment should be considered in subjects with Hb Westport.
描述一种新型β-珠蛋白变异体，该变异体通过阳离子交换 HPLC 干扰 HbA1c 分析。
使用阳离子交换 HPLC 和免疫分析即时检测分析仪评估 HbA1c 测量进行糖尿病筛查。常规血红蛋白病筛查包括 CBC、HbF 和 HbA 的测量，采用阳离子交换 HPLC 和毛细管电泳（CE）。通过 ESI TOF 质谱和 DNA 测序进一步进行变异特征分析。
我们的研究对象获得了不一致的 HbA1c 结果，阳离子交换 HPLC 测量的 HbA1c 为 52mmol/mol，而免疫分析的正常水平为 34mmol/mol。异常的 HbA1c 峰形促使进行血红蛋白病筛查，以调查潜在的变异体干扰。阳离子交换 HPLC（使用β-地中海贫血程序）和 CE 结果明显正常，HbF 和 HbA 均在参考范围内检测到。ESI TOF 质谱显示存在变异的β-珠蛋白链。在β-珠蛋白基因的密码子 121 处发现了一种新的错义变异 [β121 (GH4) Glu>Asp; HBB:c.366A>C]，我们将其命名为 Hb Westport。
Hb Westport 是一种新型的β-珠蛋白变异体，它通过 Bio-Rad D-100 阳离子交换 HPLC 干扰 HbA1c 测量，导致结果偏高。对于我们的研究对象来说，这是具有临床意义的，因为错误升高的 HbA1c 值超过了糖尿病的诊断阈值。在 Hb Westport 患者中，应考虑采用替代方法进行糖尿病评估。
