Urinary biomarker investigation in children with Fabry disease using tandem mass spectrometry

Christiane Auray-Blais, Catherine Marie Blais, Uma Ramaswami, Michel Boutin, Dominique P. Germain, Sarah Dyack, Olaf Bodamer, Guillem Pintos-Morell, Joe T R Clarke, Daniel G. Bichet, David G. Warnock, Lucia Echevarria, Michael L. West, Pamela Lavoie

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background: Fabry disease is an X-linked lysosomal storage disorder affecting both males and females with tremendous genotypic/phenotypic variability. Concentrations of globotriaosylceramide (Gb3), globotriaosylsphingosine (lyso-Gb3)/related analogues were investigated in pediatric and adult Fabry cohorts. The aims of this study were to transfer and validate an HPLC-MS/MS methodology on a UPLC-MS/MS new generation platform, using an HPLC column, for urine analysis of treated and untreated pediatric and adult Fabry patients, to establish correlations between the excretion of Fabry biomarkers with gender, treatment, types of mutations, and to evaluate the biomarker reliability for early detection of pediatric Fabry patients. Method: A UPLC-MS/MS was used for biomarker analysis. Results: Reference values are presented for all biomarkers. Results show that gender strongly influences the excretion of each biomarker in the pediatric Fabry cohort, with females having lower urinary levels of all biomarkers. Urinary distribution of lyso-Gb3/related analogues in treated Fabry males was similar to the untreated and treated Fabry female groups in both children and adult cohorts. Children with the late-onset p.N215S mutation had normal urinary levels of Gb3, and lyso-Gb3 but abnormal levels of related analogues. Conclusions: In this study, Fabry males and most Fabry females would have been diagnosed using the urinary lyso-Gb3/related analogue profile.

Original languageEnglish
Pages (from-to)195-204
Number of pages10
JournalClinica Chimica Acta
Volume438
DOIs
StatePublished - Aug 19 2014

Fingerprint

Fabry Disease
Biomarkers
Tandem Mass Spectrometry
Mass spectrometry
Pediatrics
High Pressure Liquid Chromatography
Mutation
Reference Values
Urine
globotriaosyl lysosphingolipid

Keywords

  • Biomarkers
  • Children
  • Fabry disease
  • Globotriaosylceramide
  • Globotriaosylsphingosine and analogues
  • Mass spectrometry

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Auray-Blais, C., Blais, C. M., Ramaswami, U., Boutin, M., Germain, D. P., Dyack, S., ... Lavoie, P. (2014). Urinary biomarker investigation in children with Fabry disease using tandem mass spectrometry. Clinica Chimica Acta, 438, 195-204. https://doi.org/10.1016/j.cca.2014.08.002

Urinary biomarker investigation in children with Fabry disease using tandem mass spectrometry. / Auray-Blais, Christiane; Blais, Catherine Marie; Ramaswami, Uma; Boutin, Michel; Germain, Dominique P.; Dyack, Sarah; Bodamer, Olaf; Pintos-Morell, Guillem; Clarke, Joe T R; Bichet, Daniel G.; Warnock, David G.; Echevarria, Lucia; West, Michael L.; Lavoie, Pamela.

In: Clinica Chimica Acta, Vol. 438, 19.08.2014, p. 195-204.

Research output: Contribution to journalArticle

Auray-Blais, C, Blais, CM, Ramaswami, U, Boutin, M, Germain, DP, Dyack, S, Bodamer, O, Pintos-Morell, G, Clarke, JTR, Bichet, DG, Warnock, DG, Echevarria, L, West, ML & Lavoie, P 2014, 'Urinary biomarker investigation in children with Fabry disease using tandem mass spectrometry', Clinica Chimica Acta, vol. 438, pp. 195-204. https://doi.org/10.1016/j.cca.2014.08.002
Auray-Blais C, Blais CM, Ramaswami U, Boutin M, Germain DP, Dyack S et al. Urinary biomarker investigation in children with Fabry disease using tandem mass spectrometry. Clinica Chimica Acta. 2014 Aug 19;438:195-204. https://doi.org/10.1016/j.cca.2014.08.002
Auray-Blais, Christiane ; Blais, Catherine Marie ; Ramaswami, Uma ; Boutin, Michel ; Germain, Dominique P. ; Dyack, Sarah ; Bodamer, Olaf ; Pintos-Morell, Guillem ; Clarke, Joe T R ; Bichet, Daniel G. ; Warnock, David G. ; Echevarria, Lucia ; West, Michael L. ; Lavoie, Pamela. / Urinary biomarker investigation in children with Fabry disease using tandem mass spectrometry. In: Clinica Chimica Acta. 2014 ; Vol. 438. pp. 195-204.
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abstract = "Background: Fabry disease is an X-linked lysosomal storage disorder affecting both males and females with tremendous genotypic/phenotypic variability. Concentrations of globotriaosylceramide (Gb3), globotriaosylsphingosine (lyso-Gb3)/related analogues were investigated in pediatric and adult Fabry cohorts. The aims of this study were to transfer and validate an HPLC-MS/MS methodology on a UPLC-MS/MS new generation platform, using an HPLC column, for urine analysis of treated and untreated pediatric and adult Fabry patients, to establish correlations between the excretion of Fabry biomarkers with gender, treatment, types of mutations, and to evaluate the biomarker reliability for early detection of pediatric Fabry patients. Method: A UPLC-MS/MS was used for biomarker analysis. Results: Reference values are presented for all biomarkers. Results show that gender strongly influences the excretion of each biomarker in the pediatric Fabry cohort, with females having lower urinary levels of all biomarkers. Urinary distribution of lyso-Gb3/related analogues in treated Fabry males was similar to the untreated and treated Fabry female groups in both children and adult cohorts. Children with the late-onset p.N215S mutation had normal urinary levels of Gb3, and lyso-Gb3 but abnormal levels of related analogues. Conclusions: In this study, Fabry males and most Fabry females would have been diagnosed using the urinary lyso-Gb3/related analogue profile.",
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AU - Blais, Catherine Marie

AU - Ramaswami, Uma

AU - Boutin, Michel

AU - Germain, Dominique P.

AU - Dyack, Sarah

AU - Bodamer, Olaf

AU - Pintos-Morell, Guillem

AU - Clarke, Joe T R

AU - Bichet, Daniel G.

AU - Warnock, David G.

AU - Echevarria, Lucia

AU - West, Michael L.

AU - Lavoie, Pamela

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N2 - Background: Fabry disease is an X-linked lysosomal storage disorder affecting both males and females with tremendous genotypic/phenotypic variability. Concentrations of globotriaosylceramide (Gb3), globotriaosylsphingosine (lyso-Gb3)/related analogues were investigated in pediatric and adult Fabry cohorts. The aims of this study were to transfer and validate an HPLC-MS/MS methodology on a UPLC-MS/MS new generation platform, using an HPLC column, for urine analysis of treated and untreated pediatric and adult Fabry patients, to establish correlations between the excretion of Fabry biomarkers with gender, treatment, types of mutations, and to evaluate the biomarker reliability for early detection of pediatric Fabry patients. Method: A UPLC-MS/MS was used for biomarker analysis. Results: Reference values are presented for all biomarkers. Results show that gender strongly influences the excretion of each biomarker in the pediatric Fabry cohort, with females having lower urinary levels of all biomarkers. Urinary distribution of lyso-Gb3/related analogues in treated Fabry males was similar to the untreated and treated Fabry female groups in both children and adult cohorts. Children with the late-onset p.N215S mutation had normal urinary levels of Gb3, and lyso-Gb3 but abnormal levels of related analogues. Conclusions: In this study, Fabry males and most Fabry females would have been diagnosed using the urinary lyso-Gb3/related analogue profile.

AB - Background: Fabry disease is an X-linked lysosomal storage disorder affecting both males and females with tremendous genotypic/phenotypic variability. Concentrations of globotriaosylceramide (Gb3), globotriaosylsphingosine (lyso-Gb3)/related analogues were investigated in pediatric and adult Fabry cohorts. The aims of this study were to transfer and validate an HPLC-MS/MS methodology on a UPLC-MS/MS new generation platform, using an HPLC column, for urine analysis of treated and untreated pediatric and adult Fabry patients, to establish correlations between the excretion of Fabry biomarkers with gender, treatment, types of mutations, and to evaluate the biomarker reliability for early detection of pediatric Fabry patients. Method: A UPLC-MS/MS was used for biomarker analysis. Results: Reference values are presented for all biomarkers. Results show that gender strongly influences the excretion of each biomarker in the pediatric Fabry cohort, with females having lower urinary levels of all biomarkers. Urinary distribution of lyso-Gb3/related analogues in treated Fabry males was similar to the untreated and treated Fabry female groups in both children and adult cohorts. Children with the late-onset p.N215S mutation had normal urinary levels of Gb3, and lyso-Gb3 but abnormal levels of related analogues. Conclusions: In this study, Fabry males and most Fabry females would have been diagnosed using the urinary lyso-Gb3/related analogue profile.

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