JIMD Reports, Volume 30

Sala, P Ruiz, Ruijter, G, Acquaviva, C, Chabli, A, de Sain-van der Velden, M G M, Garcia-Villoria, J, Heiner-Fokkema, M R, Jeannesson-Thivisol, E, Leckstrom, K, Franzson, L, Lynes, G, Olesen, J, Onkenhout, W, Petrou, P, Drousiotou, A, Ribes, A, Vianey-Saban, C, Merinero, B, Sala, P. Ruiz, Ruijter, G., Acquaviva, C., Chabli, A., de Sain-van der Velden, M. G. M., Garcia-Villoria, J., Heiner-Fokkema, M. R., Jeannesson-Thivisol, E., Leckstrom, K., Franzson, L., Lynes, G., Olesen, J., Onkenhout, W., Petrou, P., Drousiotou, A., Ribes, A., Vianey-Saban, C., Merinero, B., P. Ruiz Sala, G. Ruijter, C. Acquaviva, A. Chabli, M. G. M. de Sain-van der Velden, J. Garcia-Villoria, M. R. Heiner-Fokkema, E. Jeannesson-Thivisol, K. Leckstrom, L. Franzson, G. Lynes, J. Olesen, W. Onkenhout, P. Petrou, A. Drousiotou, A. Ribes, C. Vianey-Saban, B. Merinero

The analysis of acylcarnitines (AC) in plasma/serum is established as a useful test for the biochemical diagnosis and the monitoring of treatment of organic acidurias and fatty acid oxidation defects. External quality assurance (EQA) for qualitative and quantitative AC is offered by ERNDIM and CDC in dried blood spots but not in plasma/serum samples. A pilot interlaboratory comparison between 14 European laboratories was performed over 3 years using serum/plasma samples from patients with an established diagnosis of an organic aciduria or fatty acid oxidation defect. Twenty-three different samples with a short clinical description were circulated. Participants were asked to specify the method used to analyze diagnostic AC, to give quantitative data for diagnostic AC with the corresponding reference values, possible diagnosis, and advice for further investigations.Although the reference and pathological concentrations of AC varied among laboratories, elevated marker AC for propionic acidemia, isovaleric acidemia, medium-chain acyl-CoA dehydrogenase, very long-chain acyl-CoA dehydrogenase, and multiple acyl-CoA dehydrogenase deficiencies were correctly identified by all participants allowing the diagnosis of these diseases. Conversely, the increased concentrations of dicarboxylic AC were not always identified, and therefore the correct diagnosis was not reach by some participants, as exemplified in cases of malonic aciduria and 3-hydroxy-3-methylglutaryl-CoA lyase deficiency. Misinterpretation occurred in those laboratories that used multiple-reaction monitoring acquisition mode, did not derivatize, or did not separate isomers. However, some of these laboratories suggested further analyses to clarify the diagnosis.This pilot experience highlights the importance of an EQA scheme for AC in plasma.