Santes Berto Maria, Sanchez Asis Sara, Robles Bauza Juan, Rubio Alaejos Ana, Bauça Josep Miquel, Delgado Jose Antonio
Department of Laboratory Medicine, Hospital Universitari Son Espases, Palma, Spain.
Department of Laboratory Medicine, Hospital Universitari Son Espases, Palma, Spain.
Clin Chim Acta. 2025 Jan 1;564:119943. doi: 10.1016/j.cca.2024.119943. Epub 2024 Aug 25.
BACKGROUND-AIM: Methylmalonic acid (MMA) is currently the best biomarker of functional vitamin B12 deficiency. However, for a correct interpretation of the patient's results it is necessary to know its biological variation (BV). No BV data are available for urine MMA values, as measured by mass spectrometry. Hence, the aim of this study was to estimate the within- and between-person coefficients of variation (CV CV) for MMA in a healthy population, and the associated index of individuality (II), as well as to define quality specifications based on BV and the reference change value (RCV).
Random urine samples from 34 healthy volunteers were collected over four consecutive weeks. Samples were stored at -80 °C until analysis in a single analytical run. MMA excretion was quantified by tandem liquid chromatography coupled to mass spectrometry (HPLC-MS/MS). Results were normalized to urine creatinine. The coefficients of variation were estimated by CV-ANOVA. Confidence intervals (95 %) were calculated. Quality specifications were defined according to international recommendations.
A total of 128 samples were included. The coefficients of variation were CV = 35.7 % (26.1-45.3) and CV = 67.7 % (58.3-77.0). The associated II was 0.5 and the RCV was 88.1 %.
Considering the II obtained, MMA in urine has high individuality, therefore, RCV is better to evaluate serial clinical results. Our results will contribute to a better clinical interpretation of this biomarker and will represent a great aid when defining analytical performance specifications for this magnitude.
背景-目的：甲基丙二酸（MMA）是目前功能性维生素B12缺乏的最佳生物标志物。然而，为了正确解读患者的检测结果，有必要了解其生物学变异（BV）。目前尚无通过质谱法测量的尿MMA值的BV数据。因此，本研究的目的是估计健康人群中MMA的个体内和个体间变异系数（CV）以及相关的个体性指数（II），并根据BV和参考变化值（RCV）定义质量规范。
连续四周收集34名健康志愿者的随机尿样。样本保存在-80°C直至在单次分析运行中进行分析。通过串联液相色谱-质谱联用（HPLC-MS/MS）对MMA排泄进行定量。结果以尿肌酐进行标准化。变异系数通过CV-方差分析进行估计。计算95%置信区间。根据国际建议定义质量规范。
共纳入128个样本。变异系数为CV = 35.7%（26.1-45.3）和CV = 67.7%（58.3-77.0）。相关的II为0.5，RCV为88.1%。
考虑到所获得的II，尿中的MMA具有高度个体性，因此，RCV更适合评估系列临床结果。我们的结果将有助于更好地从临床角度解读该生物标志物，并在定义该指标的分析性能规范时提供很大帮助。
