LC–MS/MS progress in newborn screening

Lehotay, Denis C.; Hall, Patricia; Lepage, Joyce; Eichhorst, Jeff; Etter, Michele L.; Greenberg, Cheryl R.

doi:10.1016/j.clinbiochem.2010.08.007

Cited by 81 publications

(87 citation statements)

References 47 publications

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“…Even if the disease is not treatable, the parents are spared the necessity of visiting a long series of physicians in their uncertainty and more rapidly receive reliable advice as to whether they should have further children. 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).…”

Section: Discussionmentioning

confidence: 99%

“…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%

“…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%

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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%

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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“…This expansion has resulted from the use of tandem mass spectrometry, which allows simultaneous detection of multiple analytes from a single punch (3,14,20 ). The use of this technology provides scope for additional disorders to be added in the future (3,20 ), and as such may include other disorders that have the potential for false-negative results if samples are not of the recommended quality (21 ). The recent program expansion has resulted in the inclusion of more clinically severe conditions, which increases the likelihood that further second-tier testing will be required on the DBS.…”

Section: Discussionmentioning

confidence: 99%

“…Newborn screening (NBS) 3 is performed in many countries to allow early detection of conditions that are either life-threatening or can cause a clinically significant adverse outcome if left untreated (1)(2)(3). Dried blood spots (DBS) have been used for NBS since the early 1970s because the sample is easy to collect and transport, and the sample volume required is relatively small (4 -7 ).…”

confidence: 99%

Effect of Dried Blood Spot Quality on Newborn Screening Analyte Concentrations and Recommendations for Minimum Acceptance Criteria for Sample Analysis

George¹,

Moat

2016

Clinical Chemistry

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BACKGROUND The analysis of dried blood spots has been used routinely for newborn screening since the early 1970s, and the number of disorders screened has expanded substantially in recent years. However, there is a lack of evidence regarding minimum blood spot quality acceptance criteria for sample analysis. METHODS Blood pools were spiked with phenylalanine, tyrosine, leucine, methionine, octanoylcarnitine, decanoylcarnitine, isovalerylcarnitine, glutarylcarnitine, thyroid-stimulating hormone, and immunoreactive trypsinogen to concentrations at the analytical cutoffs used in UK screening protocols. We evaluated the effect of sample volume applied to the card (10, 20, 50, 75, and 100 μL), punch location (central vs peripheral), and sample quality (double layering, applying blood to both sides of the filter paper, multispotting, applying insufficient sample, and compressing the sample after application). RESULTS Compression of blood spots produced significantly lower results (14%–44%) for all analytes measured (P < 0.001). Smaller blood spots produced significantly lower results (15%–24% for 10-μL vs 50-μL sample size) for all analytes at all concentrations measured (P < 0.001). Results obtained from peripheral punches were higher than those from a central punch, although this did not reach statistical significance for all analytes. Insufficient and multispotted samples demonstrated heterogeneous results. CONCLUSIONS All blood spots containing ≤20 μL (blood spot diameter <8 mm), those in which blood has not fully penetrated the filter paper, and all samples with evidence of compression should be rejected, since there is a risk of producing false-negative results.

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Nutritional Metabolomics

Daniel¹

2013

Metabolomics in Practice

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LC–MS/MS progress in newborn screening

Cited by 81 publications

References 47 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

Effect of Dried Blood Spot Quality on Newborn Screening Analyte Concentrations and Recommendations for Minimum Acceptance Criteria for Sample Analysis

Nutritional Metabolomics

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