Lysosomal storage disorder 4+1 multiplex assay for newborn screening using tandem mass spectrometry

Application to a small-scale population study for five lysosomal storage disorders

Joseph J. Orsini, Monica M. Martin, Amanda L. Showers, Olaf A. Bodamer, X. Kate Zhang, Michael H. Gelb, Michele Caggana

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Background: We sought to modify a previously published tandem mass spectrometry method of screening for 5 lysosomal storage disorders (LSDs) in order to make it better suited for high-throughput newborn screening. Methods: Two 3-mm dried blood spot (DBS) punches were incubated, each with a different assay solution. The quadruplex solution was used for screening for Gaucher, Pompe, Krabbe and Fabry diseases, while a separate solution was used for Niemann-Pick A/B disease. Results: The mean activities of acid-β-glucocerebrosidase (ABG), acid sphingomyelinase (ASM), acid glucosidase (GAA), galactocerebroside-β-galactosidase (GALC) and acid-galactosidase A (GLA) were measured on 5055 unidentified newborns. The mean activities (compared with their disease controls) were, 15.1 (0.35), 22.2 (1.34), 16.8 (0.51), 3.61 (0.23), and 20.7 (1.43) (μmol/L/h), respectively. The number of specimens that fell below our retest level cutoff of < 20% daily mean activity (DMA) for each analyte is: ABG (6), ASM (0), GAA (5), GALC (17), and GLA (2). Conclusions: This method provides a simplified and reliable assay for screening for five LSDs with clear distinction between activities from normal and disease samples. Advantages of this new method include significant decreases in processing time and the number of required assay solutions and overall decreased complexity.

Original languageEnglish
Pages (from-to)1270-1273
Number of pages4
JournalClinica Chimica Acta
Volume413
Issue number15-16
DOIs
StatePublished - Aug 16 2012

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Galactosidases
Tandem Mass Spectrometry
Mass spectrometry
Assays
Screening
Acids
Sphingomyelin Phosphodiesterase
Population
Globoid Cell Leukodystrophy
Glycogen Storage Disease Type II
Glucosylceramidase
Disease control
Glucosidases
Fabry Disease
Gaucher Disease
Blood
Throughput
Processing

Keywords

  • Lysosomal storage disorder
  • Multiplex
  • Newborn screening
  • Tandem mass spectrometry

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Lysosomal storage disorder 4+1 multiplex assay for newborn screening using tandem mass spectrometry : Application to a small-scale population study for five lysosomal storage disorders. / Orsini, Joseph J.; Martin, Monica M.; Showers, Amanda L.; Bodamer, Olaf A.; Zhang, X. Kate; Gelb, Michael H.; Caggana, Michele.

In: Clinica Chimica Acta, Vol. 413, No. 15-16, 16.08.2012, p. 1270-1273.

Research output: Contribution to journalArticle

Orsini, Joseph J. ; Martin, Monica M. ; Showers, Amanda L. ; Bodamer, Olaf A. ; Zhang, X. Kate ; Gelb, Michael H. ; Caggana, Michele. / Lysosomal storage disorder 4+1 multiplex assay for newborn screening using tandem mass spectrometry : Application to a small-scale population study for five lysosomal storage disorders. In: Clinica Chimica Acta. 2012 ; Vol. 413, No. 15-16. pp. 1270-1273.
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AU - Gelb, Michael H.

AU - Caggana, Michele

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