title: Pilot Experience with an External Quality Assurance Scheme for Acylcarnitines in Plasma/Serum.
abstract: 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.
authors.affiliation: Centro de Diagnóstico de Enfermedades Moleculares, Universidad Autónoma de Madrid, IDIPAZ, CIBER de Enfermedades Raras, 28049, Madrid, Spain.
authors.forename: P Ruiz
authors.initials: PR
authors.lastname: Sala
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Ruijter
authors.affiliation: Service Maladies Héréditaires du Métabolisme, Centre de Biologie et Pathologie Est, Lyon, France.
authors.forename: C
authors.initials: C
authors.lastname: Acquaviva
authors.affiliation: Biochimie métabolomique et protéomique, Hopital Necker Enfants Malades, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Chabli
authors.affiliation: Department of Medical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: M G M
authors.initials: MG
authors.lastname: de Sain-van der Velden
authors.affiliation: Department of Biochemistry and Molecular Genetics, Div Inborn Errors Metab, Hospital Clinic, IDIBAPS, CIBERER, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Garcia-Villoria
authors.affiliation: Department of Laboratory Medicine, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: M R
authors.initials: MR
authors.lastname: Heiner-Fokkema
authors.affiliation: Service de Biochimie et Biologie Moléculaire, CHU de Nancy, Vandoeuvre-Nancy, France.
authors.forename: E
authors.initials: E
authors.lastname: Jeannesson-Thivisol
authors.affiliation: Department Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Leckstrom
authors.affiliation: Department of Genetics and Molecular Medicine, Landspitali, Reykjavik, Iceland.
authors.forename: L
authors.initials: L
authors.lastname: Franzson
authors.affiliation: Neurometabolic Unit, National Hospital for Neurology and Neurosurgery, London, UK.
authors.forename: G
authors.initials: G
authors.lastname: Lynes
authors.affiliation: Department of Clinical Genetics, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Olesen
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: W
authors.initials: W
authors.lastname: Onkenhout
authors.affiliation: Department of Biochemical Genetics, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: P
authors.initials: P
authors.lastname: Petrou
authors.affiliation: Department of Biochemical Genetics, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: A
authors.initials: A
authors.lastname: Drousiotou
authors.affiliation: Department of Biochemistry and Molecular Genetics, Div Inborn Errors Metab, Hospital Clinic, IDIBAPS, CIBERER, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Ribes
authors.affiliation: Service Maladies Héréditaires du Métabolisme, Centre de Biologie et Pathologie Est, Lyon, France.
authors.forename: C
authors.initials: C
authors.lastname: Vianey-Saban
authors.affiliation: Centro de Diagnóstico de Enfermedades Moleculares, Universidad Autónoma de Madrid, IDIPAZ, CIBER de Enfermedades Raras, 28049, Madrid, Spain. bmerinero@cbm.csic.es.
authors.forename: B
authors.initials: B
authors.lastname: Merinero
keywords: Acylcarnitines; External quality assurance; Fatty acid oxidation defects; Organic acidurias