title: 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.
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.
authors.affiliation: New York State Department of Health, Wadsworth Center, Albany, NY 12201-0509, United States. jjo01@health.state.ny.us
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Orsini
authors.forename: Monica M
authors.initials: MM
authors.lastname: Martin
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Showers
authors.forename: Olaf A
authors.initials: OA
authors.lastname: Bodamer
authors.forename: X Kate
authors.initials: XK
authors.lastname: Zhang
authors.forename: Michael H
authors.initials: MH
authors.lastname: Gelb
authors.forename: Michele
authors.initials: M
authors.lastname: Caggana
mesh_terms: D059788:Dried Blood Spot Testing; D000795:Fabry Disease / Q000175:diagnosis; D005698:Galactosylceramidase / Q000097:blood; D005776:Gaucher Disease / Q000175:diagnosis; D005962:Glucosylceramidase / Q000097:blood; D006009:Glycogen Storage Disease Type II / Q000175:diagnosis; D006801:Humans; D007231:Infant, Newborn; D007965:Leukodystrophy, Globoid Cell / Q000175:diagnosis; D016464:Lysosomal Storage Diseases / Q000097:blood / Q000175:diagnosis*; D015997:Neonatal Screening / Q000379:methods*; D009542:Niemann-Pick Diseases / Q000175:diagnosis; D011786:Quality Control; D013108:Sphingomyelin Phosphodiesterase / Q000097:blood; D053719:Tandem Mass Spectrometry / Q000379:methods*; D000520:alpha-Glucosidases / Q000097:blood
chemical_list: D013108:Sphingomyelin Phosphodiesterase; C509951:GAA protein, human; D000520:alpha-Glucosidases; D005962:Glucosylceramidase; D005698:Galactosylceramidase