title: Pilot study of newborn screening for six lysosomal storage diseases using Tandem Mass Spectrometry.
abstract: There is current expansion of newborn screening (NBS) programs to include lysosomal storage disorders because of the availability of treatments that produce an optimal clinical outcome when started early in life.
  
  
  
  To evaluate the performance of a multiplex-tandem mass spectrometry (MS/MS) enzymatic activity assay of 6 lysosomal enzymes in a NBS laboratory for the identification of newborns at risk for developing Pompe, Mucopolysaccharidosis-I (MPS-I), Fabry, Gaucher, Niemann Pick-A/B, and Krabbe diseases.
  
  
  
  Enzyme activities (acid α-glucosidase (GAA), galactocerebrosidase (GALC), glucocerebrosidase (GBA), α-galactosidase A (GLA), α-iduronidase (IDUA) and sphingomyeline phosphodiesterase-1 (SMPD-1)) were measured on ~43,000 de-identified dried blood spot (DBS) punches, and screen positive samples were submitted for DNA sequencing to obtain genotype confirmation of disease risk. The 6-plex assay was efficiently performed in the Washington state NBS laboratory by a single laboratory technician at the bench using a single MS/MS instrument. The number of screen positive samples per 100,000 newborns were as follows: GAA (4.5), IDUA (13.6), GLA (18.2), SMPD1 (11.4), GBA (6.8), and GALC (25.0).
  
  
  
  A 6-plex MS/MS assay for 6 lysosomal enzymes can be successfully performed in a NBS laboratory. The analytical ranges (enzyme-dependent assay response for the quality control HIGH sample divided by that for all enzyme-independent processes) for the 6-enzymes with the MS/MS is 5- to 15-fold higher than comparable fluorimetric assays using 4-methylumbelliferyl substrates. The rate of screen positive detection is consistently lower for the MS/MS assay compared to the fluorimetric assay using a digital microfluidics platform.
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, WA 98195, United States.
authors.forename: Susan
authors.initials: S
authors.lastname: Elliott
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, WA 98195, United States.
authors.forename: Norman
authors.initials: N
authors.lastname: Buroker
authors.affiliation: PerkinElmer, Waltham, MA 02451, United States.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Cournoyer
authors.affiliation: PerkinElmer, Waltham, MA 02451, United States.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Potier
authors.affiliation: PerkinElmer, Waltham, MA 02451, United States.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Trometer
authors.affiliation: PerkinElmer, Waltham, MA 02451, United States.
authors.forename: Carole
authors.initials: C
authors.lastname: Elbin
authors.affiliation: PerkinElmer, Waltham, MA 02451, United States.
authors.forename: Mack J
authors.initials: MJ
authors.lastname: Schermer
authors.affiliation: PerkinElmer, Turku 20750, Finland.
authors.forename: Jaana
authors.initials: J
authors.lastname: Kantola
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, WA 98195, United States.
authors.forename: Aaron
authors.initials: A
authors.lastname: Boyce
authors.affiliation: Chemistry, University of Washington, Seattle, WA 98195, United States.
authors.forename: Frantisek
authors.initials: F
authors.lastname: Turecek
authors.affiliation: Chemistry, University of Washington, Seattle, WA 98195, United States; Biochemistry, University of Washington, Seattle, WA 98195, United States. Electronic address: gelb@uw.edu.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Gelb
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, WA 98195, United States. Electronic address: crscott@u.washington.edu.
authors.forename: C Ronald
authors.initials: CR
authors.lastname: Scott
mesh_terms: D059788:Dried Blood Spot Testing; D057075:Enzyme Assays; D000795:Fabry Disease / Q000097:blood / Q000503:physiopathology; D005260:Female; D005698:Galactosylceramidase / Q000097:blood*; D005776:Gaucher Disease / Q000097:blood / Q000503:physiopathology; D005962:Glucosylceramidase / Q000097:blood*; D006009:Glycogen Storage Disease Type II / Q000097:blood / Q000503:physiopathology; D006801:Humans; D007068:Iduronidase / Q000097:blood*; D007231:Infant, Newborn; D007965:Leukodystrophy, Globoid Cell / Q000097:blood / Q000503:physiopathology; D016464:Lysosomal Storage Diseases / Q000097:blood* / Q000145:classification / Q000235:genetics / Q000473:pathology; D008297:Male; D008059:Mucopolysaccharidosis I / Q000097:blood / Q000503:physiopathology; D015997:Neonatal Screening; D009542:Niemann-Pick Diseases / Q000097:blood / Q000503:physiopathology; D013108:Sphingomyelin Phosphodiesterase / Q000097:blood*; D053719:Tandem Mass Spectrometry; D000519:alpha-Galactosidase / Q000097:blood*; D000520:alpha-Glucosidases / Q000097:blood*
chemical_list: C543066:SMPD1 protein, human; D013108:Sphingomyelin Phosphodiesterase; C509951:GAA protein, human; D000520:alpha-Glucosidases; C576330:GLA protein, human; D000519:alpha-Galactosidase; D005962:Glucosylceramidase; D005698:Galactosylceramidase; C000615655:IDUA protein, human; D007068:Iduronidase
keywords: Dried blood spot; Fabry disease; Gaucher disease; Hurler disease; Krabbe disease; Lysosomal storage disorders; Newborn screening; Niemann-Pick-A/B disease; Pompe disease; Tandem mass spectrometry