External quality assessment of urinary methylmalonic acid quantification – results of a pilot study

Abstract

Measurement of methylmalonic acid (MMA) is recognised as a useful tool in the diagnostic work-up of suspected cobalamin deficiency (1). Increased concentrations of MMA in both serum and urine are indicative of cobalamin deficiency at the tissue level. MMA measurement in serum as the sample material is convenient from a logistic point of view, since analysis can be performed using residual sample material after serum cobalamin measurement requested as a screening test. The major drawbacks of serum MMA measurement, however, are the impact of impaired renal function leading to high MMA concentrations, irrespective of individual cobalamin status (2), and the typically very low concentration range of MMA in serum samples. In urine, far higher concentrations of MMA are present compared to serum, facilitating analyses. Furthermore, calculation of the MMA/creatinine ratio can compensate impaired MMA excretion in renal failure. While external quality assessment programs for serum MMA quantification have been implemented (3), no corresponding services are available for urinary MMA measurement so far, and no commercial materials for assay calibration and quality control are available. In the January 2006 issue of Clinical Chemistry and Laboratory Medicine, we announced a pilot study on external quality assessment of urinary MMA measurement and invited laboratories to participate in this investigation. In response to this announcement, a total of ten European laboratories requested test samples, and lyophilised aliquots of four study samples were shipped. These samples were manufactured (Chromsystems GmbH, Munich, Germany) by spiking a native urine sample from a healthy volunteer (sample B) with different quantities of a pure