External quality control of urinary methyl malonic acid quantification - announcement of a pilot study.

Methylmalonic acid (MMA) accumulates in the body in cases of cobalamin (vitamin B12) deficiency because of impaired metabolization of methylmalonyl CoA to succinyl CoA by methylmalonyl CoA-mutase, a cobalamin-dependent enzyme. Therefore, MMA represents a functional marker of cobalamin deficiency (1). It is widely accepted that MMA measurement is useful and necessary if serum cobalamin concentrations between 150 and 300 pg/mL are found, overcoming the limited reliability of serum cobalamin measurement in the lower concentration range (2–4). Despite good evidence for the usefulness of MMA measurement, tests are rarely requested in many countries and are offered by only a few laboratories. This particularly applies for measurement of urinary MMA, which clearly represents the sample material of choice; impaired renal function is associated with increased serum and plasma MMA concentrations, irrespective of the cobalamin status (5). In contrast, measurement of urinary MMA concentrations and calculation of the ratio of urinary MMA to urinary creatinine is essentially independent of individual renal function. Quantification of MMA in both serum and urine is technically demanding and gas chromatography (GC) or liquid chromatography (LC) isotope dilution mass spectrometry methods are mandatory. So far, no matrix-based materials for MMA assay calibration and continuous quality control are commercially available. After initial studies (6, 7), proficiency testing programs for serum and plasma MMA measurement were implemented in Europe and the USA. For urinary MMA measurement, however, no external quality control programs have been implemented so far.