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

doi:10.1016/j.cca.2014.08.002

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

Medicine

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

61 Citas (Scopus)

Resumen

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.

Idioma original	English
Páginas (desde-hasta)	195-204
Número de páginas	10
Publicación	Clinica Chimica Acta
Volumen	438
DOI	https://doi.org/10.1016/j.cca.2014.08.002
Estado	Published - ago. 19 2014

Nota bibliográfica

Funding Information:
This research was funded by grant-in-aid of research from Genzyme (A Sanofi company), and the Canadian Institutes of Health Research ( CIHR: ISO-86229 ). We are grateful to Waters Corporation for their continued scientific support and partnership. We acknowledge our colleagues at the Canadian Fabry Disease Initiative for their support. We are thankful to all Fabry patients for their cooperation. The funding organizations played no role in the design of this study, choice of enrolled patients, review and interpretation of data, and preparation or approval of the manuscript.

Publisher Copyright:
© 2014 Elsevier B.V.

ASJC Scopus Subject Areas

Biochemistry
Clinical Biochemistry
Biochemistry, medical

PubMed: MeSH publication types

Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

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Auray-Blais, C., Blais, C. M., Ramaswami, U., Boutin, M., Germain, D. P., Dyack, S., Bodamer, O., Pintos-Morell, G., Clarke, J. T. R., Bichet, D. G., Warnock, D. G., Echevarria, L., West, M. L., & 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

@article{69a9a90442db4548a04bce0d945af5c4,

title = "Urinary biomarker investigation in children with Fabry disease using tandem mass spectrometry",

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.",

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

note = "Funding Information: This research was funded by grant-in-aid of research from Genzyme (A Sanofi company), and the Canadian Institutes of Health Research ( CIHR: ISO-86229 ). We are grateful to Waters Corporation for their continued scientific support and partnership. We acknowledge our colleagues at the Canadian Fabry Disease Initiative for their support. We are thankful to all Fabry patients for their cooperation. The funding organizations played no role in the design of this study, choice of enrolled patients, review and interpretation of data, and preparation or approval of the manuscript. Publisher Copyright: {\textcopyright} 2014 Elsevier B.V.",

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doi = "10.1016/j.cca.2014.08.002",

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T1 - Urinary biomarker investigation in children with Fabry disease using tandem mass spectrometry

AU - Auray-Blais, Christiane

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

N1 - Funding Information: This research was funded by grant-in-aid of research from Genzyme (A Sanofi company), and the Canadian Institutes of Health Research ( CIHR: ISO-86229 ). We are grateful to Waters Corporation for their continued scientific support and partnership. We acknowledge our colleagues at the Canadian Fabry Disease Initiative for their support. We are thankful to all Fabry patients for their cooperation. The funding organizations played no role in the design of this study, choice of enrolled patients, review and interpretation of data, and preparation or approval of the manuscript. Publisher Copyright: © 2014 Elsevier B.V.

PY - 2014/8/19

Y1 - 2014/8/19

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

Resumen

Nota bibliográfica

ASJC Scopus Subject Areas

PubMed: MeSH publication types

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