Abstract
Summary: As well as characteristic increases in C8 carnitine, dried blood spot samples from 11 newborns with medium-chain acyl-CoA dehydrogenase deficiency detected by tandem mass spectrometry screening using butyl esters showed apparent increases in glutarylcarnitine (m/z 388 signals). In four of the newborns in which it was measured, apparent increases in malonylcarnitine (m/z 360) were also detected. It was shown that the apparent increases were caused by interfering acylcarnitines, putatively identified as hydroxyoctanoylcarnitine and hydroxydecanoylcarnitine, respectively, using alternative derivatives for tandem mass spectrometry. Levels of the two abnormal carnitines correlated with C8 carnitine levels and normalized with repeat testing in 10 cases. These results indicated that the abnormal carnitines were significantly elevated only during periods of increased fatty acid catabolism, as may occur in the immediate postnatal period.
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REFERENCES
Andresen BS, Dobrowolski SF, O'Reilly L, et al (2001) Medium-chain acyl-CoA dehydrogenase (MCAD) mutations identified by MS/MS-based prospective screening of newborns differ from those observed in patients with clinical symptoms: identification and characterization of a new, prevalent mutation that results in mild MCAD deficiency. Am J Hum Genet 68: 1408–1418.
Carpenter KH, Wiley V (2002) Application of tandem mass spectrometry to biochemical genetics and newborn screening. Clin Chim Acta 322: 1–10.
Carpenter K, Wiley V, Sim KG, Heath D, Wilcken B (2001) Evaluation of newborn screening for medium chain acyl-CoA dehydrogenase deficiency in 275 000 babies. Arch Dis Child Fetal Neonatal Ed 85: F105–F109.
Chace DH, Kalas TA, Naylor EW (2002) The application of tandem mass spectrometry to neonatal screening for inherited disorders of intermediary metabolism. Annu Rev Genomics Hum Genet 3: 17–45.
Clayton PT, Doig M, Ghafari S, et al (1998) Screening for medium chain acyl-CoA dehydrogenase deficiency using electrospray ionisation tandem mass spectrometry. Arch Dis Child 79: 109–115.
Colle E, Mamer OA, Montgomery JA, Miller JD (1983) Episodic hypoglycemia with psi-hydroxy fatty acid excretion. Pediatr Res 17: 171–176.
Divry P, Vianey-Liaud C, Cotte J (1984) Gas chromatography-mass spectrometry (GC-MS) diagnosis of two cases of medium chain acyl-CoA dehydrogenase deficiency. J InheritMetab Dis 7(supplement 7): 44–47.
Libert R, Van Hoof F, Thillaye M, et al (1997) Identification of new medium-chain acylcarnitines present in normal human urine. Anal Biochem 251: 196–205.
Libert R, Van Hoof F, Thillaye M, et al (1999) Identification of new medium-chain acylcarnitines present in urine of a patient with medium-chain acyl-CoA dehydrogenase deficiency. J Inherit Metab Dis 22: 9–18.
Meyberg J, Schulze A, Kohlmueller D, Linderkamp O, Mayatepek E (2001) Postnatal changes in neonatal acylcarnitine profile. Pediatr Res 49: 125–129.
Naylor EW, Chace DH (1999) Automated tandem mass spectrometry for mass newborn screening for disorders in fatty acid, organic acid, and amino acid metabolism. J Child Neurol 14(supplement 1): S4–S8.
Pitt JJ (1993) Novel glycine conjugates in medium-chain acyl-CoA dehydrogenase deficiency. J Inherit Metab Dis 16: 392–398.
Rashed MS, Ozand PT, Bucknall MP, Little D (1995) Diagnosis of inborn errors of metabolism from blood spots by acylcarnitines and amino acids profiling using automated electrospray tandem mass spectrometry. Pediatr Res 38: 324–331.
Rashed MS, Bucknall MP, Little D, et al (1997) Screening blood spots for inborn errors of metabolism by electrospray tandem mass spectrometry with a microplate batch process and a computer algorithm for automated flagging of abnormal profiles. Clin Chem 43: 1129–1141.
Rinaldo P, O'Shea JJ, Welch RD, Tanaka K (1989) Stable isotope dilution analysis of n-hexanoylglycine, 3-phenylpropionylglycine and suberylglycine in human urine using chemical ionization gas chromatography/mass spectrometry selected ion monitoring. Biomed Environ Mass Spectrom 18: 471–477.
Tserng KY, Jin SJ, Kerr DS, Hoppel CL (1990) Abnormal urinary excretion of unsaturated dicarboxylic acids in patients with medium-chain acyl-CoA dehydrogenase deficiency. J Lipid Res 31: 763–771.
Turner C, Wu HY, Bird S, Dalton RN (2003) Measurement of blood spot octanoyl carnitine without derivatisation using tandem mass-spectrometry (TMS) [Abstract]. J InheritMetab Dis 26: 2.
Wiley V, Carpenter K, Wilcken B (1999) Newborn screening with tandem mass spectrometry: 12 months' experience in NSW Australia. Acta Paediatr Suppl 88: 48–51.
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Napolitano, N., Wiley, V. & Pitt, J.J. Pseudo-glutarylcarnitinaemia in medium-chain acyl-CoA dehydrogenase deficiency detected by tandem mass spectrometry newborn screening. J Inherit Metab Dis 27, 465–471 (2004). https://doi.org/10.1023/B:BOLI.0000037343.90450.8d
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DOI: https://doi.org/10.1023/B:BOLI.0000037343.90450.8d