Urine acylcarnitine analysis by ESI-MS/MS: a new tool for the diagnosis of peroxisomal biogenesis disorders

Clin Chim Acta. 2008 Dec;398(1-2):86-9. doi: 10.1016/j.cca.2008.08.018. Epub 2008 Aug 28.

Abstract

Background: Patients with peroxisomal biogenesis disorders (PBDs) have an abnormal profile of circulating acylcarnitines (i.e. elevated C16:0-DC-, C18:0-DC-, C24:0-, C26:0-carnitine). We developed an ESI-MS/MS method for quantification of urine acylcarnitines and tested its reliability for the diagnosis of PBDs.

Methods: Urine from 7 patients with PBDs (5 Zellweger syndrome, 2 infantile Refsum disease), from 2 patients with D-bifunctional protein (D-BP) deficiency, and from 130 healthy controls were analysed by ESI-MS/MS, using a multiple reactions monitoring (MRM) method, and quantified with labelled internal standards. Acylcarnitine levels between groups were analyzed by the STATA statistics data analysis and compared by the non parametric Mann-Whitney test.

Results: In PBDs, the urinary excretion of long-chain dicarboxylylcarnitines (C14:0-DC-, C16:0-DC-, and C18:0-DC-carnitine), and of very long-chain monocarboxylylcarnitines (C22:0-, C24:0-, C26:0-carnitine) were significantly elevated compared to controls (p<0.0001). Interestingly, among PBDs the most severe abnormalities of acylcarnitine profile were observed in patients with Zellweger syndrome. One patient with D-BP showed similar abnormalities to PBDs, while in the other only C16:0-DC-carnitine was markedly elevated.

Conclusions: This study shows that MRM ESI-MS/MS acylcarnitine analysis unequivocally discriminates patients with PBDs and D-BP deficiency from controls, representing a reliable and sensitive method for the diagnosis that requires a short-time analysis with high sample through-put.

MeSH terms

  • Carnitine / analogs & derivatives*
  • Carnitine / urine
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Peroxisomal Disorders / diagnosis*
  • Peroxisomal Disorders / urine*
  • Refsum Disease / diagnosis
  • Refsum Disease / urine
  • Reproducibility of Results
  • Spectrometry, Mass, Electrospray Ionization
  • Tandem Mass Spectrometry
  • Zellweger Syndrome / diagnosis
  • Zellweger Syndrome / urine

Substances

  • acylcarnitine
  • Carnitine