PMID- 27238910 OWN - NLM STAT- MEDLINE DCOM- 20171212 LR - 20210402 IS - 1096-7206 (Electronic) IS - 1096-7192 (Print) IS - 1096-7192 (Linking) VI - 118 IP - 4 DP - 2016 Aug TI - Pilot study of newborn screening for six lysosomal storage diseases using Tandem Mass Spectrometry. PG - 304-9 LID - S1096-7192(16)30090-7 [pii] LID - 10.1016/j.ymgme.2016.05.015 [doi] AB - BACKGROUND: 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. OBJECTIVE: 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. METHODS AND RESULTS: Enzyme activities (acid alpha-glucosidase (GAA), galactocerebrosidase (GALC), glucocerebrosidase (GBA), alpha-galactosidase A (GLA), alpha-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). DISCUSSION: 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. CI - Copyright (c) 2016 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Elliott, Susan AU - Elliott S AD - Department of Pediatrics, University of Washington, Seattle, WA 98195, United States. FAU - Buroker, Norman AU - Buroker N AD - Department of Pediatrics, University of Washington, Seattle, WA 98195, United States. FAU - Cournoyer, Jason J AU - Cournoyer JJ AD - PerkinElmer, Waltham, MA 02451, United States. FAU - Potier, Anna M AU - Potier AM AD - PerkinElmer, Waltham, MA 02451, United States. FAU - Trometer, Joseph D AU - Trometer JD AD - PerkinElmer, Waltham, MA 02451, United States. FAU - Elbin, Carole AU - Elbin C AD - PerkinElmer, Waltham, MA 02451, United States. FAU - Schermer, Mack J AU - Schermer MJ AD - PerkinElmer, Waltham, MA 02451, United States. FAU - Kantola, Jaana AU - Kantola J AD - PerkinElmer, Turku 20750, Finland. FAU - Boyce, Aaron AU - Boyce A AD - Department of Pediatrics, University of Washington, Seattle, WA 98195, United States. FAU - Turecek, Frantisek AU - Turecek F AD - Chemistry, University of Washington, Seattle, WA 98195, United States. FAU - Gelb, Michael H AU - Gelb MH AD - Chemistry, University of Washington, Seattle, WA 98195, United States; Biochemistry, University of Washington, Seattle, WA 98195, United States. Electronic address: gelb@uw.edu. FAU - Scott, C Ronald AU - Scott CR AD - Department of Pediatrics, University of Washington, Seattle, WA 98195, United States. Electronic address: crscott@u.washington.edu. LA - eng GR - R01 DK067859/DK/NIDDK NIH HHS/United States PT - Journal Article DEP - 20160520 PL - United States TA - Mol Genet Metab JT - Molecular genetics and metabolism JID - 9805456 RN - EC 3.1.4.12 (SMPD1 protein, human) RN - EC 3.1.4.12 (Sphingomyelin Phosphodiesterase) RN - EC 3.2.1.20 (GAA protein, human) RN - EC 3.2.1.20 (alpha-Glucosidases) RN - EC 3.2.1.22 (GLA protein, human) RN - EC 3.2.1.22 (alpha-Galactosidase) RN - EC 3.2.1.45 (Glucosylceramidase) RN - EC 3.2.1.46 (Galactosylceramidase) RN - EC 3.2.1.76 (IDUA protein, human) RN - EC 3.2.1.76 (Iduronidase) SB - IM MH - Dried Blood Spot Testing MH - Enzyme Assays MH - Fabry Disease/blood/physiopathology MH - Female MH - Galactosylceramidase/*blood MH - Gaucher Disease/blood/physiopathology MH - Glucosylceramidase/*blood MH - Glycogen Storage Disease Type II/blood/physiopathology MH - Humans MH - Iduronidase/*blood MH - Infant, Newborn MH - Leukodystrophy, Globoid Cell/blood/physiopathology MH - Lysosomal Storage Diseases/*blood/classification/genetics/pathology MH - Male MH - Mucopolysaccharidosis I/blood/physiopathology MH - Neonatal Screening MH - Niemann-Pick Diseases/blood/physiopathology MH - Sphingomyelin Phosphodiesterase/*blood MH - Tandem Mass Spectrometry MH - alpha-Galactosidase/*blood MH - alpha-Glucosidases/*blood PMC - PMC5318163 MID - NIHMS849461 OTO - NOTNLM OT - Dried blood spot OT - Fabry disease OT - Gaucher disease OT - Hurler disease OT - Krabbe disease OT - Lysosomal storage disorders OT - Newborn screening OT - Niemann-Pick-A/B disease OT - Pompe disease OT - Tandem mass spectrometry EDAT- 2016/05/31 06:00 MHDA- 2017/12/13 06:00 PMCR- 2017/02/20 CRDT- 2016/05/31 06:00 PHST- 2016/03/29 00:00 [received] PHST- 2016/05/19 00:00 [revised] PHST- 2016/05/19 00:00 [accepted] PHST- 2016/05/31 06:00 [entrez] PHST- 2016/05/31 06:00 [pubmed] PHST- 2017/12/13 06:00 [medline] PHST- 2017/02/20 00:00 [pmc-release] AID - S1096-7192(16)30090-7 [pii] AID - 10.1016/j.ymgme.2016.05.015 [doi] PST - ppublish SO - Mol Genet Metab. 2016 Aug;118(4):304-9. doi: 10.1016/j.ymgme.2016.05.015. Epub 2016 May 20.