A biochemical perspective on the use of tandem mass spectrometry for newborn screening and clinical testing

Chace, Donald H.; Kalas, Theodore A.

doi:10.1016/j.clinbiochem.2005.01.017

Cited by 147 publications

(89 citation statements)

References 37 publications

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“…Moreover, prenatal diagnosis may then be possible in subsequent pregnancies (Lehotay et al 2011). Screening for metabolic disorders may be based on tandem MS (Lehotay et al 2011;Chace and Kalas 2005) or NMR (Engelke et al 2008;Wevers et al 1999). Although tandem-MS is more frequently used, NMR possesses several advantages.…”

Section: Discussionmentioning

confidence: 99%

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NMR-Based Screening for Inborn Errors of Metabolism: Initial Results from a Study on Turkish Neonates

et al. 2014

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Approximately 1 in 400 neonates in Turkey is affected by inherited metabolic diseases. This high prevalence is at least in part due to consanguineous marriages. Standard screening in Turkey now covers only three metabolic diseases (phenylketonuria, congenital hypothyroidism, and biotinidase deficiency). Once symptoms have developed, tandem-MS can be used, although this currently covers only up to 40 metabolites. NMR potentially offers a rapid and versatile alternative.We conducted a multi-center clinical study in 14 clinical centers in Turkey. Urine samples from 989 neonates were collected and investigated by using NMR spectroscopy in two different laboratories. The primary objective of the present study was to explore the range of variation of concentration and chemical shifts of specific metabolites without clinically relevant findings that can be detected in the urine of Turkish neonates. The secondary objective was the integration of the results from a healthy reference population of neonates into an NMR database, for routine and completely automatic screening of congenital metabolic diseases.Both targeted and untargeted analyses were performed on the data. Targeted analysis was aimed at 65 metabolites. Limits of detection and quantitation were determined by generating urine spectra, in which known concentrations of the analytes were added electronically as well as by real spiking. Untargeted analysis involved analysis of the whole spectrum for abnormal features, using statistical procedures, including principal component analysis. Outliers were eliminated by model building. Untargeted analysis was used to detect known and unknown compounds and jaundice, proteinuria, and acidemia. The results will be used to establish a database to detect pathological concentration ranges and for routine screening.

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Section: Discussionmentioning

confidence: 99%

“…Numerous additional diseases are just tested by tandem-MS once symptoms have developed; however, this technique currently uses a maximum of 40 metabolites, as only 40 reference substances are available for quantification (Lehotay et al 2011;Chace and Kalas 2005).…”

Section: Introductionmentioning

confidence: 99%

NMR-Based Screening for Inborn Errors of Metabolism: Initial Results from a Study on Turkish Neonates

et al. 2014

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“…Such blood spots are prepared shortly after birth by spotting a drop of newborn blood onto a filter paper card and allowing the liquid to dry on the card. It is now commonplace in many countries to send dried blood spots to newborn screening laboratories for tandem MS analysis of amino acids and acylcarnitines (see, for example, Chace and Kalas (2005), Wilcken et al (2003)). Quantification of these compounds allows screening for up to about 30 treatable metabolic diseases.…”

Section: Tandem Mass Spectrometry For the Multiplex Analysis Of Lysosmentioning

confidence: 99%

Direct multiplex assay of enzymes in dried blood spots by tandem mass spectrometry for the newborn screening of lysosomal storage disorders

Gelb

Tureček

Scott

et al. 2006

J of Inher Metab Disea

187

140

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SummaryTandem mass spectrometry is currently used in newborn screening programmes to quantify the level of amino acids and acylcarnitines in dried blood spots for detection of metabolites associated with treatable diseases. We have developed assays for lysosomal enzymes in re-hydrated dried blood spots in which a set of substrates is added and the set of corresponding enzymatic products are quantified using tandem mass spectrometry with the aid of mass-differentiated internal standards. We have developed a multiplex assay of the set of enzymes that, when deficient, cause the lysosomal storage disorders Fabry, Gaucher, Hurler, Krabbe, Niemann-Pick A/B and Pompe diseases. These diseases were selected because treatments are now available or expected to emerge shortly. The discovery that acarbose is a selective inhibitor of maltase glucoamylase allows the Pompe disease enzyme, acid α-glucosidase, to be selectively assayed in white blood cells and dried blood spots. When tested with dried blood spots from 40 unaffected individuals and 10-12 individuals with the lysosomal storage disorder, the tandem mass spectrometry assay led to the correct identification of the affected individuals with 100% sensitivity. Many of the reagents needed for the new assays are commercially available, and those that are not are being prepared under Good Manufacturing Procedures for approval by the FDA. Our newborn screening assay for Krabbe disease is currently being put in place at the Wadsworth Center in New York State for the analysis of ~1000 dried blood spots per day.Summary We have developed tandem mass spectrometry for the direct assay of lysosomal enzymes in rehydrated dried blood spots that can be implemented for newborn screening of lysosomal storage disorders. Several enzymes can be analysed by a single method (multiplex analysis) and in a highthroughput manner appropriate for newborn screening laboratories.

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“…Mass spectrometry (MS) is a well established tool for quantification of metabolites in clinical samples [8,9]. With the development of soft ionization techniques [10,11], it is now possible to extend its application to quantifying peptide components of biomarker candidates in clinical samples.…”

Section: Introductionmentioning

confidence: 99%

Antibody-based enrichment of peptides on magnetic beads for mass-spectrometry-based quantification of serum biomarkers

Whiteaker

Zhao

Zhang

et al. 2007

Analytical Biochemistry

256

208

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A major bottleneck for validation of new clinical diagnostics is the development of highly sensitive and specific assays for quantifying proteins. We previously described a method, Stable Isotope Standards with Capture by Anti-Peptide Antibodies, wherein a specific tryptic peptide is selected as a stoichiometric representative of the protein from which it is cleaved, is enriched from biological samples using immobilized antibodies, and is quantitated using mass spectrometry against a spiked internal standard to yield a measure of protein concentration. In this report, we optimize a magnetic bead-based platform amenable to high throughput peptide capture and demonstrate that antibody capture followed by mass spectrometry can achieve ion signal enhancements on the order of 10 3 , with precision (CVs <10%) and accuracy (relative error ~20%) sufficient for quantifying biomarkers in the physiologically relevant ng/mL range. These methods are generally applicable to any protein or biological fluid of interest and hold great potential for providing a desperately needed bridging technology between biomarker discovery and clinical application.

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A biochemical perspective on the use of tandem mass spectrometry for newborn screening and clinical testing

Cited by 147 publications

References 37 publications

NMR-Based Screening for Inborn Errors of Metabolism: Initial Results from a Study on Turkish Neonates

NMR-Based Screening for Inborn Errors of Metabolism: Initial Results from a Study on Turkish Neonates

Direct multiplex assay of enzymes in dried blood spots by tandem mass spectrometry for the newborn screening of lysosomal storage disorders

Antibody-based enrichment of peptides on magnetic beads for mass-spectrometry-based quantification of serum biomarkers

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