Axis-Shield Diagnostics, Dundee, UK.
Clin Chem. 2011 Jun;57(6):856-63. doi: 10.1373/clinchem.2010.158154. Epub 2011 Apr 11.
Vitamin B₁₂ deficiency is common among the elderly, and early detection is clinically important. However, clinical signs and symptoms have limited diagnostic accuracy and there is no accepted reference test method.
In elderly subjects (n = 700; age range 63-97 years), we investigated the ability of serum cobalamin, holotranscobalamin (holoTC), total homocysteine (tHcy), methylmalonic acid (MMA), serum and erythrocyte folate, and other hematologic variables to discriminate cobalamin deficiency, defined as red blood cell cobalamin <33 pmol/L.
Serum holoTC was the best predictor, with area under the ROC curve (95% CI) 0.90 (0.86-0.93), and this was significantly better (P ≤ 0.0002) than the next best predictors; serum cobalamin, 0.80 (0.75-0.85), and MMA, 0.78 (0.72-0.83). For these 3 analytes, we constructed a 3-zone partition of positive and negative zones and a deliberate indeterminate zone between. The boundaries were values of each test that resulted in a posttest probability of deficiency of 60% and a posttest probability of no deficiency of 98%. The proportion of indeterminate observations for holoTC, cobalamin, and MMA was 14%, 45%, and 50%, respectively. Within the holoTC indeterminate zone (defined as 20-30 pmol/L), discriminant analysis selected only erythrocyte folate, which correctly allocated 65% (58/89) of the observations. Renal dysfunction compromised the diagnostic accuracy of MMA but not holoTC or serum cobalamin.
This study supports the use of holoTC as the first-line diagnostic procedure for vitamin B₁₂ status.
维生素 B₁₂ 缺乏在老年人中很常见，早期发现具有重要的临床意义。然而，临床症状和体征的诊断准确性有限，且目前尚无被广泛认可的参考检测方法。
我们对 700 名（年龄 63-97 岁）老年受试者进行了研究，检测了血清钴胺素、全钴胺素（holoTC）、总同型半胱氨酸（tHcy）、甲基丙二酸（MMA）、血清和红细胞叶酸以及其他血液学变量对维生素 B₁₂ 缺乏（定义为红细胞钴胺素 <33 pmol/L）的诊断能力。
血清 holoTC 是最佳预测指标，ROC 曲线下面积（95%CI）为 0.90（0.86-0.93），显著优于下一个最佳预测指标（血清钴胺素，0.80 [0.75-0.85]）和 MMA（0.78 [0.72-0.83]）。对于这 3 种分析物，我们构建了一个 3 区分区的阳性和阴性区以及一个有意的不确定区。边界是每个测试的数值，使缺陷的后验概率为 60%，无缺陷的后验概率为 98%。holoTC、钴胺素和 MMA 的不确定观察比例分别为 14%、45%和 50%。在 holoTC 不确定区（定义为 20-30 pmol/L）内，判别分析仅选择红细胞叶酸，正确分配了 65%（58/89）的观察值。肾功能不全降低了 MMA 的诊断准确性，但不影响 holoTC 或血清钴胺素。
本研究支持将 holoTC 作为维生素 B₁₂ 状态的一线诊断方法。
