Pilot study of newborn screening for six lysosomal storage diseases using Tandem Mass Spectrometry

被引：115

作者：

Elliott, Susan ^{[1
]}

Buroker, Norman ^{[1
]}

Cournoyer, Jason J. ^{[2
]}

Potier, Anna M. ^{[2
]}

Trometer, Joseph D. ^{[2
]}

Elbin, Carole ^{[2
]}

Schermer, Mack J. ^{[2
]}

Kantola, Jaana ^{[5
]}

Boyce, Aaron ^{[1
]}

Turecek, Frantisek ^{[3
]}

Gelb, Michael H. ^{[3
,4
]}

Scott, C. Ronald ^{[1
]}

机构：

[1] Univ Washington, Dept Pediat, Seattle, WA 98195 USA

[2] PerkinElmer, Waltham, MA 02451 USA

[3] Univ Washington, Chem, Seattle, WA 98195 USA

[4] Univ Washington, Biochem, Seattle, WA 98195 USA

[5] PerkinElmer, Turku 20750, Finland

来源：

MOLECULAR GENETICS AND METABOLISM | 2016年 / 118卷 / 04期

关键词：

Newborn screening; Lysosomal storage disorders; Gaucher disease; Krabbe disease; Hurler disease; Pompe disease; Fabry disease; Niemann-Pick-A/B disease; Tandem mass spectrometry; Dried blood spot; DRIED BLOOD SPOTS; FILTER-PAPER; ENZYMATIC DIAGNOSIS; MUCOPOLYSACCHARIDOSIS-I; RETROSPECTIVE DIAGNOSES; ASSAY; ENZYMES; FABRY; DISORDERS; CARDS;

D O I：

10.1016/j.ymgme.2016.05.015

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 a-glucosidase (GAA), galactocerebrosidase (GALC), glucocerebrosidase (GBA), alpha-galactosidase A (CIA), alpha-iduronidase (IDUA) and sphingomyeline phosphodiesterase-1 (SMPD-1)) were measured on similar to 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: GM (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. (C) 2016 The Authors. Published by Elsevier Inc.

引用

页码：304 / 309

页数：6

共 28 条

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