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

Guglielmo Duranti, Sara Boenzi, Cristiano Rizzo, Lucilla Ravà, Vincenzo Di Ciommo, Rosalba Carrozzo, Maria Chiara Meschini, David W. Johnson, Carlo Dionisi-Vici

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)86-89
Number of pages4
JournalClinica Chimica Acta
Volume398
Issue number1-2
DOIs
Publication statusPublished - Dec 2008

Fingerprint

Peroxisomal Disorders
Carnitine
Urine
Zellweger Syndrome
Protein Deficiency
Infantile Refsum's Disease
Proteins
Monitoring
acylcarnitine
Statistics

Keywords

  • Acylcarnitines
  • ESI-MS/MS
  • Infantile Refsum disease
  • Peroxisomal biogenesis disorders
  • Tandem mass spectrometry
  • Zellweger syndrome

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Urine acylcarnitine analysis by ESI-MS/MS : A new tool for the diagnosis of peroxisomal biogenesis disorders. / Duranti, Guglielmo; Boenzi, Sara; Rizzo, Cristiano; Ravà, Lucilla; Di Ciommo, Vincenzo; Carrozzo, Rosalba; Meschini, Maria Chiara; Johnson, David W.; Dionisi-Vici, Carlo.

In: Clinica Chimica Acta, Vol. 398, No. 1-2, 12.2008, p. 86-89.

Research output: Contribution to journalArticle

Duranti, Guglielmo ; Boenzi, Sara ; Rizzo, Cristiano ; Ravà, Lucilla ; Di Ciommo, Vincenzo ; Carrozzo, Rosalba ; Meschini, Maria Chiara ; Johnson, David W. ; Dionisi-Vici, Carlo. / Urine acylcarnitine analysis by ESI-MS/MS : A new tool for the diagnosis of peroxisomal biogenesis disorders. In: Clinica Chimica Acta. 2008 ; Vol. 398, No. 1-2. pp. 86-89.
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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.",
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T2 - A new tool for the diagnosis of peroxisomal biogenesis disorders

AU - Duranti, Guglielmo

AU - Boenzi, Sara

AU - Rizzo, Cristiano

AU - Ravà, Lucilla

AU - Di Ciommo, Vincenzo

AU - Carrozzo, Rosalba

AU - Meschini, Maria Chiara

AU - Johnson, David W.

AU - Dionisi-Vici, Carlo

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N2 - 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.

AB - 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.

KW - Acylcarnitines

KW - ESI-MS/MS

KW - Infantile Refsum disease

KW - Peroxisomal biogenesis disorders

KW - Tandem mass spectrometry

KW - Zellweger syndrome

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