Newborn screening for Fabry disease by measuring GLA activity using tandem mass spectrometry

Angéla Dajnoki, György Fekete, Joan Keutzer, Joseph J. Orsini, Victor R. De Jesus, Yin Hsiu Chien, Wuh Liang Hwu, Zoltan Lukacs, Adolf Mühl, X. Kate Zhang, Olaf Bodamer

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Abstract

Background: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by the deficiency of α-galactosidase A (GLA). We evaluated a tandem mass spectrometry method to measure GLA activity. Methods: One 3.2. mm punch from a dried blood spot sample (DBS) was incubated with substrate and internal standard in the reaction buffer for 22. h. The resulting product was quantified against internal standard using MS/MS. Results: The median GLA activity of male newborn DBS (N=5025) was 9.85 ± 6.4 μmol/h/l (CI 95% is 9.67-10.02 μmol/h/l); The median GLA activity of female newborns (N=4677) was 10.2 ± 6.3 μmol/h/l (CI 95% is 10.02-10.38 μmol/h/l). The difference between the two subgroups is within assay analytical variation. The GLA activities in the DBS samples from 9 juvenile and adult males with previously identified FD were below 1.64 μmol/h/l. The GLA activities from 32 juvenile and adult females with confirmed FD were below 4.73 μmol/h/l. In 5 (16%) females GLA activities were above the 0.5th percentile of lower limit of CI 95% at 3.18 μmol/h/l. Conclusions: The MS/MS method for Fabry disease newborn screening is robust and can be readily multiplexed with other lysosomal disorders such as Pompe, Gaucher, Niemann-Pick, and Krabbe diseases.

Original languageEnglish
Pages (from-to)1428-1431
Number of pages4
JournalClinica Chimica Acta
Volume411
Issue number19-20
DOIs
StatePublished - Oct 1 2010

Fingerprint

Galactosidases
Fabry Disease
Tandem Mass Spectrometry
Mass spectrometry
Screening
Blood
Niemann-Pick Diseases
Globoid Cell Leukodystrophy
Assays
Buffers
Substrates

Keywords

  • Dried blood
  • Fabry disease
  • Galactosidase
  • Newborn screening
  • Tandem mass spectrometry

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Dajnoki, A., Fekete, G., Keutzer, J., Orsini, J. J., De Jesus, V. R., Chien, Y. H., ... Bodamer, O. (2010). Newborn screening for Fabry disease by measuring GLA activity using tandem mass spectrometry. Clinica Chimica Acta, 411(19-20), 1428-1431. https://doi.org/10.1016/j.cca.2010.03.009

Newborn screening for Fabry disease by measuring GLA activity using tandem mass spectrometry. / Dajnoki, Angéla; Fekete, György; Keutzer, Joan; Orsini, Joseph J.; De Jesus, Victor R.; Chien, Yin Hsiu; Hwu, Wuh Liang; Lukacs, Zoltan; Mühl, Adolf; Zhang, X. Kate; Bodamer, Olaf.

In: Clinica Chimica Acta, Vol. 411, No. 19-20, 01.10.2010, p. 1428-1431.

Research output: Contribution to journalArticle

Dajnoki, A, Fekete, G, Keutzer, J, Orsini, JJ, De Jesus, VR, Chien, YH, Hwu, WL, Lukacs, Z, Mühl, A, Zhang, XK & Bodamer, O 2010, 'Newborn screening for Fabry disease by measuring GLA activity using tandem mass spectrometry', Clinica Chimica Acta, vol. 411, no. 19-20, pp. 1428-1431. https://doi.org/10.1016/j.cca.2010.03.009
Dajnoki A, Fekete G, Keutzer J, Orsini JJ, De Jesus VR, Chien YH et al. Newborn screening for Fabry disease by measuring GLA activity using tandem mass spectrometry. Clinica Chimica Acta. 2010 Oct 1;411(19-20):1428-1431. https://doi.org/10.1016/j.cca.2010.03.009
Dajnoki, Angéla ; Fekete, György ; Keutzer, Joan ; Orsini, Joseph J. ; De Jesus, Victor R. ; Chien, Yin Hsiu ; Hwu, Wuh Liang ; Lukacs, Zoltan ; Mühl, Adolf ; Zhang, X. Kate ; Bodamer, Olaf. / Newborn screening for Fabry disease by measuring GLA activity using tandem mass spectrometry. In: Clinica Chimica Acta. 2010 ; Vol. 411, No. 19-20. pp. 1428-1431.
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abstract = "Background: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by the deficiency of α-galactosidase A (GLA). We evaluated a tandem mass spectrometry method to measure GLA activity. Methods: One 3.2. mm punch from a dried blood spot sample (DBS) was incubated with substrate and internal standard in the reaction buffer for 22. h. The resulting product was quantified against internal standard using MS/MS. Results: The median GLA activity of male newborn DBS (N=5025) was 9.85 ± 6.4 μmol/h/l (CI 95{\%} is 9.67-10.02 μmol/h/l); The median GLA activity of female newborns (N=4677) was 10.2 ± 6.3 μmol/h/l (CI 95{\%} is 10.02-10.38 μmol/h/l). The difference between the two subgroups is within assay analytical variation. The GLA activities in the DBS samples from 9 juvenile and adult males with previously identified FD were below 1.64 μmol/h/l. The GLA activities from 32 juvenile and adult females with confirmed FD were below 4.73 μmol/h/l. In 5 (16{\%}) females GLA activities were above the 0.5th percentile of lower limit of CI 95{\%} at 3.18 μmol/h/l. Conclusions: The MS/MS method for Fabry disease newborn screening is robust and can be readily multiplexed with other lysosomal disorders such as Pompe, Gaucher, Niemann-Pick, and Krabbe diseases.",
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AU - Fekete, György

AU - Keutzer, Joan

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AU - De Jesus, Victor R.

AU - Chien, Yin Hsiu

AU - Hwu, Wuh Liang

AU - Lukacs, Zoltan

AU - Mühl, Adolf

AU - Zhang, X. Kate

AU - Bodamer, Olaf

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N2 - Background: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by the deficiency of α-galactosidase A (GLA). We evaluated a tandem mass spectrometry method to measure GLA activity. Methods: One 3.2. mm punch from a dried blood spot sample (DBS) was incubated with substrate and internal standard in the reaction buffer for 22. h. The resulting product was quantified against internal standard using MS/MS. Results: The median GLA activity of male newborn DBS (N=5025) was 9.85 ± 6.4 μmol/h/l (CI 95% is 9.67-10.02 μmol/h/l); The median GLA activity of female newborns (N=4677) was 10.2 ± 6.3 μmol/h/l (CI 95% is 10.02-10.38 μmol/h/l). The difference between the two subgroups is within assay analytical variation. The GLA activities in the DBS samples from 9 juvenile and adult males with previously identified FD were below 1.64 μmol/h/l. The GLA activities from 32 juvenile and adult females with confirmed FD were below 4.73 μmol/h/l. In 5 (16%) females GLA activities were above the 0.5th percentile of lower limit of CI 95% at 3.18 μmol/h/l. Conclusions: The MS/MS method for Fabry disease newborn screening is robust and can be readily multiplexed with other lysosomal disorders such as Pompe, Gaucher, Niemann-Pick, and Krabbe diseases.

AB - Background: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by the deficiency of α-galactosidase A (GLA). We evaluated a tandem mass spectrometry method to measure GLA activity. Methods: One 3.2. mm punch from a dried blood spot sample (DBS) was incubated with substrate and internal standard in the reaction buffer for 22. h. The resulting product was quantified against internal standard using MS/MS. Results: The median GLA activity of male newborn DBS (N=5025) was 9.85 ± 6.4 μmol/h/l (CI 95% is 9.67-10.02 μmol/h/l); The median GLA activity of female newborns (N=4677) was 10.2 ± 6.3 μmol/h/l (CI 95% is 10.02-10.38 μmol/h/l). The difference between the two subgroups is within assay analytical variation. The GLA activities in the DBS samples from 9 juvenile and adult males with previously identified FD were below 1.64 μmol/h/l. The GLA activities from 32 juvenile and adult females with confirmed FD were below 4.73 μmol/h/l. In 5 (16%) females GLA activities were above the 0.5th percentile of lower limit of CI 95% at 3.18 μmol/h/l. Conclusions: The MS/MS method for Fabry disease newborn screening is robust and can be readily multiplexed with other lysosomal disorders such as Pompe, Gaucher, Niemann-Pick, and Krabbe diseases.

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