Application of Mass Spectrometry in Newborn Screening: About Both Small Molecular Diseases and Lysosomal Storage Diseases

2012 ◽  
pp. 177-196 ◽  
Author(s):  
Wuh-Liang Hwu ◽  
Yin-Hsiu Chien ◽  
Ni-Chung Lee ◽  
Shiao-Fang Wang ◽  
Shu-Chuan Chiang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Newborn Screening ◽  
Lysosomal Storage Diseases ◽  
Lysosomal Storage ◽  
Storage Diseases

scholarly journals Tandem Mass Spectrometry Has a Larger Analytical Range than Fluorescence Assays of Lysosomal Enzymes: Application to Newborn Screening and Diagnosis of Mucopolysaccharidoses Types II, IVA, and VI

2015 ◽  
Vol 61 (11) ◽  
pp. 1363-1371 ◽  
Author(s):  
Arun Babu Kumar ◽  
Sophia Masi ◽  
Farideh Ghomashchi ◽  
Naveen Kumar Chennamaneni ◽  
Makoto Ito ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Newborn Screening ◽  
Lysosomal Enzymes ◽  
Lysosomal Storage Diseases ◽  
Tandem Mass ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
Mps Ii ◽  
Analytical Range ◽  
Screening And Diagnosis

Abstract BACKGROUND There is interest in newborn screening and diagnosis of lysosomal storage diseases because of the development of treatment options that improve clinical outcome. Assays of lysosomal enzymes with high analytical range (ratio of assay response from the enzymatic reaction divided by the assay response due to nonenzymatic processes) are desirable because they are predicted to lead to a lower rate of false positives in population screening and to more accurate diagnoses. METHODS We designed new tandem mass spectrometry (MS/MS) assays that give the largest analytical ranges reported to date for the use of dried blood spots (DBS) for detection of mucopolysaccharidoses type II (MPS-II), MPS-IVA, and MPS-VI. For comparison, we carried out fluorometric assays of 6 lysosomal enzymes using 4-methylumbelliferyl (4MU)-substrate conjugates. RESULTS The MS/MS assays for MPS-II, -IVA, and -VI displayed analytical ranges that are 1–2 orders of magnitude higher than those for the corresponding fluorometric assays. The relatively small analytical ranges of the 4MU assays are due to the intrinsic fluorescence of the 4MU substrates, which cause high background in the assay response. CONCLUSIONS These highly reproducible MS/MS assays for MPS-II, -IVA, and -VI can support multiplex newborn screening of these lysosomal storage diseases. MS/MS assays of lysosomal enzymes outperform 4MU fluorometric assays in terms of analytical range. Ongoing pilot studies will allow us to gauge the impact of the increased analytical range on newborn screening performance.

Detecting multiple lysosomal storage diseases by tandem mass spectrometry — A national newborn screening program in Taiwan

2014 ◽  
Vol 431 ◽  
pp. 80-86 ◽  
Author(s):  
Hsuan-Chieh Liao ◽  
Chuan-Chi Chiang ◽  
Dau-Ming Niu ◽  
Chung-Hsing Wang ◽  
Shu-Min Kao ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Screening Program ◽  
Lysosomal Storage Diseases ◽  
Tandem Mass ◽  
Lysosomal Storage ◽  
Newborn Screening Program ◽  
Storage Diseases

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

2016 ◽  
Vol 118 (4) ◽  
pp. 304-309 ◽  
Author(s):  
Susan Elliott ◽  
Norman Buroker ◽  
Jason J. Cournoyer ◽  
Anna M. Potier ◽  
Joseph D. Trometer ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Pilot Study ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Lysosomal Storage Diseases ◽  
Tandem Mass ◽  
Lysosomal Storage ◽  
Storage Diseases

scholarly journals Dataset and standard operating procedure for newborn screening of six lysosomal storage diseases: By tandem mass spectrometry

Data in Brief ◽  
2016 ◽  
Vol 8 ◽  
pp. 915-924 ◽  
Author(s):  
Susan Elliott ◽  
Norman Buroker ◽  
Jason J. Cournoyer ◽  
Anna M. Potier ◽  
Joseph D. Trometer ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Operating Procedure ◽  
Standard Operating Procedure ◽  
Lysosomal Storage Diseases ◽  
Tandem Mass ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
Standard Operating

scholarly journals Multiplex Tandem Mass Spectrometry Enzymatic Activity Assay for Newborn Screening of the Mucopolysaccharidoses and Type 2 Neuronal Ceroid Lipofuscinosis

2017 ◽  
Vol 63 (6) ◽  
pp. 1118-1126 ◽  
Author(s):  
Yang Liu ◽  
Fan Yi ◽  
Arun Babu Kumar ◽  
Naveen Kumar Chennamaneni ◽  
Xinying Hong ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Neuronal Ceroid Lipofuscinosis ◽  
Lysosomal Storage Diseases ◽  
Tandem Mass ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
Ceroid Lipofuscinosis

Abstract BACKGROUND We expanded the use of tandem mass spectrometry combined with liquid chromatography (LC-MS/MS) for multiplex newborn screening of seven lysosomal enzymes in dried blood spots (DBS). The new assays are for enzymes responsible for the mucopolysaccharidoses (MPS-I, -II, -IIIB, -IVA, -VI, and -VII) and type 2 neuronal ceroid lipofuscinosis (LINCL). METHODS New substrates were prepared and characterized for tripeptidyl peptidase 1 (TPP1), α-N-acetylglucosaminidase (NAGLU), and lysosomal β-glucuronidase (GUSB). These assays were combined with previously developed assays to provide a multiplex LC-MS/MS assay of 7 lysosomal storage diseases. Multiple reaction monitoring of ion dissociations for enzyme products and deuterium-labeled internal standards was used to quantify the enzyme activities. RESULTS Deidentified DBS samples from 62 nonaffected newborns were analyzed to simultaneously determine (run time 2 min per DBS) the activities of TPP1, NAGLU, and GUSB, along with those for α-iduronidase (IDUA), iduronate-2-sulfatase (I2S), N-acetylgalactosamine-6-sulfatase (GALNS), and N-acetylgalactosamine-4-sulfatase (ARSB). The activities measured in the 7-plex format showed assay response-to-blank-activity ratios (analytical ranges) of 102–909 that clearly separated healthy infants from affected children. CONCLUSIONS The new multiplex assay provides a robust comprehensive newborn screening assay for the mucopolysaccharidoses. The method has been expanded to include additional lysosomal storage diseases.

scholarly journals Newborn Screening for Lysosomal Storage Diseases

2015 ◽  
Vol 61 (2) ◽  
pp. 335-346 ◽  
Author(s):  
Michael H Gelb ◽  
C Ronald Scott ◽  
Frantisek Turecek
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Lysosomal Storage Diseases ◽  
Small Scale ◽  
Screening Methods ◽  
Tandem Mass ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
Direct Assay

Abstract BACKGROUND There is worldwide interest in newborn screening for lysosomal storage diseases because of the development of treatment options that give better results when carried out early in life. Screens with high differentiation between affected and nonaffected individuals are critical because of the large number of potential false positives. CONTENT This review summarizes 3 screening methods: (a) direct assay of enzymatic activities using tandem mass spectrometry or fluorometry, (b) immunocapture-based measurement of lysosomal enzyme abundance, and (c) measurement of biomarkers. Assay performance is compared on the basis of small-scale studies as well as on large-scale pilot studies of mass spectrometric and fluorometric screens. SUMMARY Tandem mass spectrometry and fluorometry techniques for direct assay of lysosomal enzymatic activity in dried blood spots have emerged as the most studied approaches. Comparative mass spectrometry vs fluorometry studies show that the former better differentiates between nonaffected vs affected individuals. This in turn leads to a manageable number of screen positives that can be further evaluated with second-tier methods.

scholarly journals The New York pilot newborn screening program for lysosomal storage diseases: Report of the First 65,000 Infants

2018 ◽  
Vol 21 (3) ◽  
pp. 631-640 ◽  
Author(s):  
Melissa P. Wasserstein ◽  
Michele Caggana ◽  
Sean M. Bailey ◽  
Robert J. Desnick ◽  
Lisa Edelmann ◽  
...  
Keyword(s):  
New York ◽  
Newborn Screening ◽  
Screening Program ◽  
Lysosomal Storage Diseases ◽  
Lysosomal Storage ◽  
Newborn Screening Program ◽  
Storage Diseases

scholarly journals Newborn screening for Morquio disease and other lysosomal storage diseases: results from the 8-plex assay for 70,000 newborns

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Yin-Hsiu Chien ◽  
Ni-Chung Lee ◽  
Pin-Wen Chen ◽  
Hui-Ying Yeh ◽  
Michael H. Gelb ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Lysosomal Storage Diseases ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
Morquio Disease

Lysosomal Newborn Screening in a Cohort in Mexican Population-

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5581-5581
Author(s):  
Juana Ines Navarrete
Keyword(s):  
Early Detection ◽  
Newborn Screening ◽  
Fabry Disease ◽  
Pompe Disease ◽  
Neonatal Screening ◽  
Inborn Errors Of Metabolism ◽  
Lysosomal Storage Diseases ◽  
Lysosomal Storage ◽  
Inborn Errors ◽  
Storage Diseases

Abstract INTRODUCTION: The goal of newborn screening is an early detection of inborn erros of metabolism diseases. In Mexico we began newborn screening since 1977 with very few inborn errors of metabolism such as phenylketonuria, galactosemia, congenital hypothyroidism, sickle cell anemia and cytic fibrosis (1). Since that date we have been increasing our newborn screening our newborn screening slowly and now a days we screen in most states of the country 15 inborn errors of metabolism(2). In 2012 we started with some patients through out the country a wider neonatal screening that include 5 lysosomal storage diseases. MATERIAL AND METHODS: Petróleos Mexicanos is a big governmental institution with approximately 10,000 workers and their families. Since 2005 a larger newborn screening has been done to all newborns in this institution through all the country. We test for most aminoacidopathies, including acidurias, hemoglobinopathies, G6PD deficiency, adrenal hyperplasia, cystic fibrosis and biotinidase deficiency; since August 2012 we included 6 lysosomal storage diseases; Gaucher disease, Fabry disease, Hurler disease, Pompe disease, Niemann-Pick type A and B disease and Krabbe disease. RESULTS: Up to date we have screened 10,853 newborns, we have found 9 patients with lysosomal storage diseases. We found 4 newborns with mutations for Fabry disease, 4 newborns with Pompe disease, three were pseudodeficiencies and one was combined heterozygous for a late onset presentation and pseudodeficiencies and 1 patient with Hurler disease (Table 2). We present here our clinical correlation between genotype-phenotype in these patients. We found a frequency in our population of 1 in 2713 newborns for both Fabry and Pompe disease. DISCUSSION: Newborn screening is a major public health achievement that has improve the morbidity and mortality of inborn errors of metabolism. The introduction of newborn screening for lysosomal storage diseases presents new challenges. This is the first latinamerican study of early detection of lysosomal storage diseases made by neonatal screening there are about 11 similar international studies. It is important point out that the most common lysosomal storage disease found in our study was Pompe diseases the pseudodeficiency type and Fabry disease type II with a frequency of 1 in 2713 newborns for both diseases. Spada et al; and Hwu et al; have reported frequencies of 1 in 1250 to 3100 male newborns. The mutation most commonly found was c.1088G>A, (p.R363H) for Fabry disease and c.1726G>A(p.G576S) for Pompe disease. References: 1. Nakamura K, Am J Med Genet Part C, 2011; 157, 63-71. 2. Zhou et al, J. Pediatr 2011 159 1 7-13. 3. Alterescu GM, Clin. Genet 2001:60:46-51. 2001. 4. Desnick R. J.: Enzyme Replacement Therapy and Enhancement therapies for Lysosomal Storage Diseases. J. Inher Metab Dis 2004; 27:385-4013. Disclosures No relevant conflicts of interest to declare.

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