Miller Luke, Maddahi Yaniv, Shelly Matthew, Nanda Sudip, Ishaq Arastu Mohammad
Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Department of Cardiology, St. Luke's University Health Network, Bethlehem, PA 18015, USA.
JCEM Case Rep. 2024 Dec 26;3(1):luae242. doi: 10.1210/jcemcr/luae242. eCollection 2025 Jan.
Routine serum studies in a female patient with sustained prediabetic glycated hemoglobin A (HbA) levels, controlled on metformin, yielded an unexpected finding: an elevated HbA value of ≥14.9% (≥139 mmol/mol) (normal reference range, <5.7% to <39 mmol/mol). Estimated average glucose (EAG) (normal reference range, <126 mg/dL to <7 mmol/L) is a linearly corresponding blood glucose value calculated from HbA measurements that reflects the average glycemic status over the preceding 3 months. Caution must be used when the EAG provided by the HbA does not align with blood glucose values obtained around the same period. Our patient carries a rare heterozygous pathogenic variant affecting the β subunit called hemoglobin Graz (Hb Graz), characterized by a histidine for leucine substitution, resulting in clinically silent Hb abnormalities. Individuals without diabetes carrying the Hb Graz pathogenic variant exhibit significantly higher HbA values when analyzed by high-performance liquid chromatography. Alternative methods of quantifying glycemic control are suggested if the possibility of a confounding variable exists, such as when a HbA-blood glucose mismatch occurs or unexplainable HbA levels are detected.
在一名女性患者中，其糖化血红蛋白A（HbA）处于糖尿病前期持续水平，通过二甲双胍治疗得到控制，常规血清检查有一项意外发现：HbA值升高至≥14.9%（≥139 mmol/mol）（正常参考范围，<5.7%至<39 mmol/mol）。估计平均血糖（EAG）（正常参考范围，<126 mg/dL至<7 mmol/L）是根据HbA测量值计算得出的线性对应血糖值，反映过去3个月的平均血糖状态。当HbA提供的EAG与同期获得的血糖值不一致时，必须谨慎对待。我们的患者携带一种罕见的杂合致病性变异，影响β亚基，称为血红蛋白格拉茨（Hb Graz），其特征是组氨酸替代亮氨酸，导致临床上无症状的Hb异常。通过高效液相色谱分析，携带Hb Graz致病性变异的非糖尿病个体表现出显著更高的HbA值。如果存在混杂变量的可能性，如出现HbA - 血糖不匹配或检测到无法解释的HbA水平时，建议采用其他量化血糖控制的方法。
