Newborn screening for X-linked adrenoleukodystrophy (X-ALD): Validation of a combined liquid chromatography-tandem mass spectrometric (LC-MS/MS) method

Walter C Hubbard, Ann B. Moser, Anita C. Liu, Richard O. Jones, Steven J Steinberg, Fred Lorey, Susan R. Panny, Robert F. Vogt, Daniela Macaya, Coleman T. Turgeon, Silvia Tortorelli, Gerald V. Raymond

Research output: Contribution to journalArticlepeer-review

103 Scopus citations


Newborn screening for X-linked adrenoleukodystrophy (X-ALD) has until now been limited in implementation because of the lack of an accepted standard methodology. We have previously reported a technique using LC-MS/MS analysis that could provide the basis for screening of newborns for X-ALD. The target analyte diagnostic for X-ALD and other peroxisomal disorders of peroxisomal β-oxidation is 1-hexacosanoyl-2-lyso-sn-3-glycero-phosphorylcholine (26:0-lyso-PC). We report here the validation of the analytical method using an authentic standard of the target compound. The method possesses sensitivity of <1.0 fmole injected on column with a correlation coefficient (R2) of 0.9987. A tetradeuterated analog of 26:0-lyso-PC served as the internal standard. The sensitivity of this clinical method was confirmed using 17 newborn samples of individuals with peroxisomal disorders retrieved from state newborn screening programs. These samples were run masked with over 1000 newborn samples. All affected individuals were identified with one exception. One sample which was retrieved as an affected did not have the biochemical or genetic abnormality of X-ALD and thus is considered an error in sample identity. These studies clearly show that the method is highly sensitive and accurate in identifying individuals with a defect in peroxisomal β-oxidation such as X-ALD.

Original languageEnglish (US)
Pages (from-to)212-220
Number of pages9
JournalMolecular genetics and metabolism
Issue number3
StatePublished - Jul 2009


  • 1-Hexacosanoyl-2-lysophosphorylcholine (26:0-lyso-PC)
  • Combined liquid chromatography-tandem mass spectrometry (LC-MS/MS)
  • Lyso-phosphatidyl-choline (lyso-PC)
  • Multiple reaction monitoring (MRM)
  • Newborn screening
  • Peroxisomal disorders
  • Phospholipids
  • X-ALD

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology


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