Bolann

Klee

Lindgren

Lorenzl

Moller

Pfeiffer

Stover

English

Vogeser, Michael

Müller, Wilhelm

Lorenzl, Stefan

Universität München: Elektronischen Publikationen

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

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

Open Access LMU ( Ludwig-Maximilians-Univ. München)

Clin Chem Lab Med 2006;44(1):123–124  2006 by Walter de Gruyter • Berlin • New York. DOI 10.1515/CCLM.2006.023 2006/405Article in press - uncorrected proofLetter to the EditorExternal quality control of urinary methyl malonic acidquantification – announcement of a pilot studyMichael Vogeser1,*, Wilhelm Mu¨ller2 andStefan Lorenzl31 Institute of Clinical Chemistry, Hospital of theUniversity of Munich, Munich, Germany2 Chromsystems GmbH, Munich, Germany3 Clinic of Neurology, Hospital of the University ofMunich, Munich, GermanyKeywords: cobalamin; methylmalonic acid; qualitycontrol; urine.Methylmalonic acid (MMA) accumulates in the bodyin cases of cobalamin (vitamin B12) deficiency be-cause of impaired metabolization of methylmalonylCoA to succinyl CoA by methylmalonyl CoA-mutase,a cobalamin-dependent enzyme. Therefore, MMArepresents a functional marker of cobalamin deficien-cy (1). It is widely accepted that MMA measurementis useful and necessary if serum cobalamin concen-trations between 150 and 300 pg/mL are found, over-coming the limited reliability of serum cobalaminmeasurement in the lower concentration range (2–4).Despite good evidence for the usefulness of MMAmeasurement, tests are rarely requested in manycountries and are offered by only a few laboratories.This particularly applies for measurement of urinaryMMA, which clearly represents the sample materialof choice; impaired renal function is associated withincreased serum and plasma MMA concentrations,irrespective of the cobalamin status (5). In contrast,measurement of urinary MMA concentrations and cal-culation of the ratio of urinary MMA to urinary cre-atinine is essentially independent of individual renalfunction.Quantification of MMA in both serum and urine istechnically demanding and gas chromatography (GC)or liquid chromatography (LC) isotope dilution massspectrometry methods are mandatory. So far, nomatrix-based materials for MMA assay calibrationand continuous quality control are commerciallyavailable. After initial studies (6, 7), proficiency testingprograms for serum and plasma MMA measurementwere implemented in Europe and the USA. For uri-nary MMA measurement, however, no external qual-ity control programs have been implemented so far.*Corresponding author: Michael Vogeser, Institute ofClinical Chemistry, Hospital of the University of Munich,Marchioninistr. 15, 81377 Munich, GermanyPhone: q49-89-70953221, Fax: q49-89-70953240,E-mail: michael.vogeser@med.uni-muenchen.deWith this letter we would like to announce an inter-national pilot project for the implementation of aproficiency testing program for urinary MMA meas-urement. The main objective of this study is to assessthe reliability of analytical methods used for MMAmeasurement and to investigate the degree of inter-laboratory variability of urinary MMA measurement.Such data are important for the interpretation ofMMAresults by clinicians.For the purpose of this study, pooled urine samplesof four MMA concentration levels have been preparedin a professional setting (Chromsystems GmbH,Munich, Germany). Samples are lyophilized and canbe shipped by regular postal services. Readers ofClinical Chemistry and Laboratory Medicine are invit-ed to join this pilot study. If they decide to do so, theyare asked to send an e-mail to Michael Vogeser, Uni-versity of Munich (michael.vogeser@med.uni-muen-chen.de) up until March 31, 2005 with the detailedpostal address of the participating laboratory; sam-ples will be shipped within 1 week. Analysis resultscan be submitted via e-mail. Six weeks after the endof the shipment period the results will be processedand the data (with mean concentrations reported anddistribution of results) will be sent to the participants.The identity of the participants will not be given toany third party.It is planned to submit the results of this pilot studyas an article to Clinical Chemistry and LaboratoryMedicine. Demonstration of close inter-laboratoryagreement of urinary MMA measurement by aninternational survey is, in our opinion, essential toincrease the limited acceptance of urinary MMAmeasurement by clinicians, and thus has the potentialto improve patient care.AcknowledgementsThe study is supported by the Hans-Fischer-Gesellschaft,Munich, Germany.References1. Stover PJ. Physiology of folate and vitamin B12 in healthand disease. Nutr Rev 2004;62:S3–12.2. Bolann BJ, Solli JD, Schneede J, Grottum KA, Loraas A,Stokkeland M, et al. Evaluation of indicators of cobalamindeficiency defined as cobalamin-induced reduction inincreased serum methylmalonic acid. Clin Chem 2000;46:1744–50.Bereitgestellt von | Universitaetsbibliothek der LMU MuenchenAngemeldet | 129.187.254.47Heruntergeladen am | 18.11.13 11:10124 Vogeser et al.: Pilot EQA of urinary MMAArticle in press - uncorrected proof3. Klee GG. Cobalamin and folate evaluation: measurementof methylmalonic acid and homocysteine vs. vitaminB(12) and folate. Clin Chem 2000;46:1277–83.4. Lorenzl S, Vogeser M, Muller-Schunk S, Pfister HW. Clin-ically and MRI documented funicular myelosis in a patientwith metabolical vitamin B12 deficiency but normal vita-min B12 serum level. J Neurol 2003;250:1010–1.5. Lindgren A. Elevated serum methylmalonic acid. Howmuch comes from cobalamin deficiency and how muchcomes from the kidneys? Scand J Clin Lab Invest 2002;62:15–20.6. Moller J, Rasmussen K, Christensen L. External qualityassessment of methylmalonic acid and total homocys-teine. Clin Chem 1999;45:1536–42.7. Pfeiffer CM, Smith SJ, Miller DT, Gunter EW. Comparisonof serum and plasma methylmalonic acid measurementsin 13 laboratories: an international study. Clin Chem1999;45:2236–42.Bereitgestellt von | Universitaetsbibliothek der LMU MuenchenAngemeldet | 129.187.254.47Heruntergeladen am | 18.11.13 11:10

Clinically and MRI documented funicular myelosis in a patient with metabolical vitamin B12 deficiency but normal vitamin B12 serum level.

Cobalamin and folate evaluation: measurement of methylmalonic acid and homocysteine vs. vitamin B(12) and folate.

Comparison of serum and plasma methylmalonic acid measurements in 13 laboratories: an international study.

Elevated serum methylmalonic acid. How much comes from cobalamin deficiency and how much comes from the kidneys? Scand J Clin Lab Invest

Evaluation of indicators of cobalamin deficiency defined as cobalamin-induced reduction in increased serum methylmalonic acid. Clin Chem

External quality assessment of methylmalonic acid and total homocysteine. Clin Chem 1999;45:1536–42.

Physiology of folate and vitamin B12 in health and disease. Nutr Rev

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

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