Acylcarnitines: analysis in plasma and whole blood using tandem mass spectrometry.

The acylcarnitine profile is a diagnostic test for inherited disorders of fatty acid and branched-chain amino acid catabolism. Patients with this type of metabolic disorder accumulate disease-specific acylcarnitines that correlate with the acyl coenzyme A compounds in the affected mitochondrial metabolic pathways. For example, propionylcarnitine accumulates in patients with both propionic and methylmalonic acidemias. The test identifies and quantifies the species of acylcarnitines in the whole blood or blood plasma of patients at risk for or suspected of having such a disorder. The acylcarnitines are analyzed using electrospray ionization-tandem mass spectrometry. The instrument is used in the precursor ion scan mode to record the molecular species giving rise to fragment ions at m/z 99, derived specifically from the methylated acylcarnitines within the specimen. Quantification is based on the principle of stable isotope dilution, whereby concentrations are derived from the response ratio of each acylcarnitine species to that of a deuterium-labeled acylcarnitine standard. Interpretation of the acylcarnitine profile requires recognition of abnormal concentrations of specific analytes or patterns of analytes and knowledge of their metabolic origin.

[1]  Yuan-Tsong Chen,et al.  ENU mutagenesis identifies mice with cardiac fibrosis and hepatic steatosis caused by a mutation in the mitochondrial trifunctional protein beta-subunit. , 2006, Human molecular genetics.

[2]  D. Millington,et al.  Tandem Mass Spectrometry in Clinical Diagnosis , 2003 .

[3]  D. Millington,et al.  Assay for free and total carnitine in human plasma using tandem mass spectrometry. , 2000, Clinical chemistry.

[4]  D. Chace,et al.  Use of tandem mass spectrometry for multianalyte screening of dried blood specimens from newborns. , 2003, Clinical chemistry.

[5]  D. Millington,et al.  Carnitine and Acylcarnitines in Metabolic Disease Diagnosis and Management , 1992 .

[6]  Svati H Shah,et al.  A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. , 2009, Cell metabolism.

[7]  R. Wanders,et al.  Characteristic Acylcarnitine Profiles in Inherited Defects of Peroxisome Biogenesis: A Novel Tool for Screening Diagnosis Using Tandem Mass Spectrometry , 2003, Pediatric Research.

[8]  G. Enns,et al.  Glutaryl-CoA dehydrogenase deficiency and newborn screening: retrospective analysis of a low excretor provides further evidence that some cases may be missed. , 2005, Molecular genetics and metabolism.

[9]  C. Hoppel,et al.  Quantification of carnitine and acylcarnitines in biological matrices by HPLC electrospray ionization-mass spectrometry. , 2008, Clinical chemistry.

[10]  R. Wanders,et al.  Quantitative acylcarnitine profiling in fibroblasts using [U-13C] palmitic acid: an improved tool for the diagnosis of fatty acid oxidation defects. , 1999, Clinica chimica acta; international journal of clinical chemistry.

[11]  Piero Rinaldo,et al.  Acylcarnitine profile analysis , 2008, Genetics in Medicine.

[12]  W Harry Hannon,et al.  Naming and Counting Disorders (Conditions) Included in Newborn Screening Panels , 2006, Pediatrics.

[13]  D. Turnbull,et al.  Quantitation of acyl-CoA and acylcarnitine esters accumulated during abnormal mitochondrial fatty acid oxidation. , 1991, The Journal of biological chemistry.

[14]  D. Millington,et al.  The tandem mass spectrometry newborn screening experience in North Carolina: 1997–2005 , 2006, Journal of Inherited Metabolic Disease.

[15]  C. Roe,et al.  Detection of gene defects in branched-chain amino acid metabolism by tandem mass spectrometry of carnitine esters produced by cultured fibroblasts. , 2000, Methods in Enzymology.