Measurement of psychosine in dried blood spots — a possible improvement to newborn screening programs for Krabbe disease

Coleman T. Turgeon, Joseph J. Orsini, Karen A. Sanders, Mark J. Magera, Thomas J. Langan, Maria L. Escolar, Patricia Duffner, Devin Oglesbee, Dimitar Gavrilov, Silvia Tortorelli, Piero Rinaldo, Kimiyo Raymond, Dietrich Matern

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Background: Newborn screening (NBS) for Krabbe disease (KD) in New York and Missouri is conducted by measuring galactocerebrosidase (GALC) activity using tandem mass spectrometry (MS/MS). These NBS efforts have shown that the incidence of KD is unexpectedly low (1:400,000) while many individuals (ca. 1:6000) with reduced GALC activity and genotypes of uncertain significance are detected and subjected to follow up testing. Psychosine (PSY) is a putative marker of KD progression and can be measured in dried blood spots (DBS). We sought to determine the role that PSY levels play in NBS for KD, follow up, and treatment monitoring. Methods: PSY was eluted from DBS with methanol containing N,N-dimethyl-D-erythro-sphingosine as internal standard (IS). Liquid chromatography-MS/MS was conducted over 17 minutes in the multiple reaction monitoring positive mode to follow the precursor to product species transitions for PSY and IS. Separation of the structural isomers PSY and glucosylsphingosine was accomplished by hydrophilic interaction liquid chromatography. Results: Pre-analytical and analytical factors were studied and revealed satisfactory results. PSY was also measured in DBS collected from controls (range: <8 nmol/L, N = 220), KD patients at various disease stages (range: 8–112, N = 26), and GALC mutation carriers (range: <15 nmol/L, N = 18). Conclusions: PSY measurement in DBS could serve as a 2nd tier assay in NBS for KD, simplify and reduce the cost of follow up protocols, help determine disease progression, and be used to monitor KD patients following hematopoietic stem cell transplantation. However, additional chronological measurements of PSY in KD patients are required to confirm these possibilities.

Original languageEnglish (US)
Pages (from-to)923-929
Number of pages7
JournalJournal of Inherited Metabolic Disease
Volume38
Issue number5
DOIs
StatePublished - Oct 1 2015

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Psychosine
Globoid Cell Leukodystrophy
Newborn Infant
Galactosylceramidase
Liquid Chromatography
Disease Progression
Hematopoietic Stem Cell Transplantation
Tandem Mass Spectrometry
Hydrophobic and Hydrophilic Interactions
Methanol
Genotype

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Turgeon, C. T., Orsini, J. J., Sanders, K. A., Magera, M. J., Langan, T. J., Escolar, M. L., ... Matern, D. (2015). Measurement of psychosine in dried blood spots — a possible improvement to newborn screening programs for Krabbe disease. Journal of Inherited Metabolic Disease, 38(5), 923-929. https://doi.org/10.1007/s10545-015-9822-z

Measurement of psychosine in dried blood spots — a possible improvement to newborn screening programs for Krabbe disease. / Turgeon, Coleman T.; Orsini, Joseph J.; Sanders, Karen A.; Magera, Mark J.; Langan, Thomas J.; Escolar, Maria L.; Duffner, Patricia; Oglesbee, Devin; Gavrilov, Dimitar; Tortorelli, Silvia; Rinaldo, Piero; Raymond, Kimiyo; Matern, Dietrich.

In: Journal of Inherited Metabolic Disease, Vol. 38, No. 5, 01.10.2015, p. 923-929.

Research output: Contribution to journalArticle

Turgeon, CT, Orsini, JJ, Sanders, KA, Magera, MJ, Langan, TJ, Escolar, ML, Duffner, P, Oglesbee, D, Gavrilov, D, Tortorelli, S, Rinaldo, P, Raymond, K & Matern, D 2015, 'Measurement of psychosine in dried blood spots — a possible improvement to newborn screening programs for Krabbe disease', Journal of Inherited Metabolic Disease, vol. 38, no. 5, pp. 923-929. https://doi.org/10.1007/s10545-015-9822-z
Turgeon, Coleman T. ; Orsini, Joseph J. ; Sanders, Karen A. ; Magera, Mark J. ; Langan, Thomas J. ; Escolar, Maria L. ; Duffner, Patricia ; Oglesbee, Devin ; Gavrilov, Dimitar ; Tortorelli, Silvia ; Rinaldo, Piero ; Raymond, Kimiyo ; Matern, Dietrich. / Measurement of psychosine in dried blood spots — a possible improvement to newborn screening programs for Krabbe disease. In: Journal of Inherited Metabolic Disease. 2015 ; Vol. 38, No. 5. pp. 923-929.
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abstract = "Background: Newborn screening (NBS) for Krabbe disease (KD) in New York and Missouri is conducted by measuring galactocerebrosidase (GALC) activity using tandem mass spectrometry (MS/MS). These NBS efforts have shown that the incidence of KD is unexpectedly low (1:400,000) while many individuals (ca. 1:6000) with reduced GALC activity and genotypes of uncertain significance are detected and subjected to follow up testing. Psychosine (PSY) is a putative marker of KD progression and can be measured in dried blood spots (DBS). We sought to determine the role that PSY levels play in NBS for KD, follow up, and treatment monitoring. Methods: PSY was eluted from DBS with methanol containing N,N-dimethyl-D-erythro-sphingosine as internal standard (IS). Liquid chromatography-MS/MS was conducted over 17 minutes in the multiple reaction monitoring positive mode to follow the precursor to product species transitions for PSY and IS. Separation of the structural isomers PSY and glucosylsphingosine was accomplished by hydrophilic interaction liquid chromatography. Results: Pre-analytical and analytical factors were studied and revealed satisfactory results. PSY was also measured in DBS collected from controls (range: <8 nmol/L, N = 220), KD patients at various disease stages (range: 8–112, N = 26), and GALC mutation carriers (range: <15 nmol/L, N = 18). Conclusions: PSY measurement in DBS could serve as a 2nd tier assay in NBS for KD, simplify and reduce the cost of follow up protocols, help determine disease progression, and be used to monitor KD patients following hematopoietic stem cell transplantation. However, additional chronological measurements of PSY in KD patients are required to confirm these possibilities.",
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AU - Turgeon, Coleman T.

AU - Orsini, Joseph J.

AU - Sanders, Karen A.

AU - Magera, Mark J.

AU - Langan, Thomas J.

AU - Escolar, Maria L.

AU - Duffner, Patricia

AU - Oglesbee, Devin

AU - Gavrilov, Dimitar

AU - Tortorelli, Silvia

AU - Rinaldo, Piero

AU - Raymond, Kimiyo

AU - Matern, Dietrich

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N2 - Background: Newborn screening (NBS) for Krabbe disease (KD) in New York and Missouri is conducted by measuring galactocerebrosidase (GALC) activity using tandem mass spectrometry (MS/MS). These NBS efforts have shown that the incidence of KD is unexpectedly low (1:400,000) while many individuals (ca. 1:6000) with reduced GALC activity and genotypes of uncertain significance are detected and subjected to follow up testing. Psychosine (PSY) is a putative marker of KD progression and can be measured in dried blood spots (DBS). We sought to determine the role that PSY levels play in NBS for KD, follow up, and treatment monitoring. Methods: PSY was eluted from DBS with methanol containing N,N-dimethyl-D-erythro-sphingosine as internal standard (IS). Liquid chromatography-MS/MS was conducted over 17 minutes in the multiple reaction monitoring positive mode to follow the precursor to product species transitions for PSY and IS. Separation of the structural isomers PSY and glucosylsphingosine was accomplished by hydrophilic interaction liquid chromatography. Results: Pre-analytical and analytical factors were studied and revealed satisfactory results. PSY was also measured in DBS collected from controls (range: <8 nmol/L, N = 220), KD patients at various disease stages (range: 8–112, N = 26), and GALC mutation carriers (range: <15 nmol/L, N = 18). Conclusions: PSY measurement in DBS could serve as a 2nd tier assay in NBS for KD, simplify and reduce the cost of follow up protocols, help determine disease progression, and be used to monitor KD patients following hematopoietic stem cell transplantation. However, additional chronological measurements of PSY in KD patients are required to confirm these possibilities.

AB - Background: Newborn screening (NBS) for Krabbe disease (KD) in New York and Missouri is conducted by measuring galactocerebrosidase (GALC) activity using tandem mass spectrometry (MS/MS). These NBS efforts have shown that the incidence of KD is unexpectedly low (1:400,000) while many individuals (ca. 1:6000) with reduced GALC activity and genotypes of uncertain significance are detected and subjected to follow up testing. Psychosine (PSY) is a putative marker of KD progression and can be measured in dried blood spots (DBS). We sought to determine the role that PSY levels play in NBS for KD, follow up, and treatment monitoring. Methods: PSY was eluted from DBS with methanol containing N,N-dimethyl-D-erythro-sphingosine as internal standard (IS). Liquid chromatography-MS/MS was conducted over 17 minutes in the multiple reaction monitoring positive mode to follow the precursor to product species transitions for PSY and IS. Separation of the structural isomers PSY and glucosylsphingosine was accomplished by hydrophilic interaction liquid chromatography. Results: Pre-analytical and analytical factors were studied and revealed satisfactory results. PSY was also measured in DBS collected from controls (range: <8 nmol/L, N = 220), KD patients at various disease stages (range: 8–112, N = 26), and GALC mutation carriers (range: <15 nmol/L, N = 18). Conclusions: PSY measurement in DBS could serve as a 2nd tier assay in NBS for KD, simplify and reduce the cost of follow up protocols, help determine disease progression, and be used to monitor KD patients following hematopoietic stem cell transplantation. However, additional chronological measurements of PSY in KD patients are required to confirm these possibilities.

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