scholarly journals Newborn screening for sickle cell disorders using tandem mass spectrometry: three years’ experience of using a protocol to detect only the disease states

2017 ◽  
Vol 54 (5) ◽  
pp. 601-611 ◽  
Author(s):  
Stuart J Moat ◽  
Derek Rees ◽  
Roanna S George ◽  
Lawrence King ◽  
Alan Dodd ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Sickle Cell ◽  
Tandem Mass ◽  
Wild Type ◽  
Disease States ◽  
Age Related ◽  
Screening Protocol ◽  
Sickle Cell Disorders

Background Tandem mass spectrometry (MS/MS) has recently become an alternative method for the newborn screening of sickle cell disorders (SCD), as it is able to detect haemoglobin (Hb) peptides following digestion of bloodspots with trypsin. Using the SpOtOn Diagnostics Reagent Kit, we previously developed a screening protocol to detect only the disease states of SCD, using action values based on the ratio between the variant Hb peptide to wild-type peptide abundances for the HbS, C, DPunjab, OArab, E and Lepore peptides. Methods Action values using the ratios between the wild type HbA (ßT1-3) peptides and the foetal Hb (γT2) peptide were developed to identify bloodspot samples from premature and transfused infants. An evaluation was undertaken to assess the transferability of the action values onto an additional MS/MS instrument. We report here our experience using this MS/MS protocol. Results During a three-year period, we screened 100,456 babies and identified 10 SCD cases (1 HbS/HPFH, 5 HbS/S and 4 HbS/C) and a case of HbE/ß-thalassaemia that was identified as a by-product. The Hb variant to wild-type peptide ratio action values were transferable to a second MS/MS instrument. Our protocol prevented the identification of an estimated 810 carrier infants. Gestational age-related action values for HbA to HbF peptide ratios were required to minimize the number of samples referred for second-line testing to exclude ß-thalassaemia. Conclusion MS/MS is a robust alternative screening technology for SCD; in addition, it also optimizes the use of equipment and expertise that currently exist in newborn screening laboratories.

Newborn screening by tandem mass spectrometry confirms the high prevalence of sickle cell disease among German newborns

2018 ◽  
Vol 98 (1) ◽  
pp. 47-53 ◽  
Author(s):  
Stephan Lobitz ◽  
Jeannette Klein ◽  
Annemarie Brose ◽  
Oliver Blankenstein ◽  
Claudia Frömmel
Keyword(s):  
Mass Spectrometry ◽  
Sickle Cell Disease ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Sickle Cell ◽  
Tandem Mass ◽  
Cell Disease ◽  
High Prevalence

Newborn screening and molecular features of patients with multiple acyl-CoA dehydrogenase deficiency in Quanzhou, China

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Yiming Lin ◽  
Weifeng Zhang ◽  
Zhixu Chen ◽  
Chunmei Lin ◽  
Weihua Lin ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Genetic Analysis ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Dehydrogenase Deficiency ◽  
Late Onset ◽  
False Negative ◽  
Tandem Mass ◽  
Lipid Storage Myopathy ◽  
Molecular Features

Abstract Objectives Multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder of fatty acid, amino acid and choline metabolism. Late-onset MADD is caused by ETFDH mutations and is the most common lipid storage myopathy in China. However, few patients with MADD have been identified through newborn screening (NBS). This study assessed the acylcarnitine profiles and molecular features of patients with MADD identified through NBS. Methods From January 2014 to June 2020, 479,786 newborns screened via tandem mass spectrometry were recruited for this study. Newborns with elevated levels of multiple acylcarnitines were recalled, those who tested positive in the reassessment were referred for genetic analysis. Results Of 479,786 newborns screened, six were diagnosed with MADD. The MADD incidence in the Chinese population was estimated to be 1:79,964. Initial NBS revealed five patients with typical elevations in the levels of multiple acylcarnitines; however, in one patient, acylcarnitine levels were in the normal reference range during recall. Notably, one patient only exhibited a mildly increased isovalerylcarnitine (C5) level at NBS. The patient with an atypical acylcarnitine profile was diagnosed with MADD by targeted gene sequencing. Six distinct ETFDH missense variants were identified, with the most common variant being c.250G>A (p.A84T), with an allelic frequency of 58.35 (7/12). Conclusions These findings revealed that it is easy for patients with MADD to go unidentified, as they may have atypical acylcarnitine profiles at NBS and the recall stage, indicating the value of genetic analysis for confirming suspected inherited metabolic disorders in the NBS program. Therefore, false-negative (FN) results may be reduced by combining tandem mass spectrometry (MS/MS) with genetic testing in NBS for MADD.

scholarly journals Comparison of tandem mass spectrometry to fluorimetry for newborn screening of LSDs

2017 ◽  
Vol 12 ◽  
pp. 80-81 ◽  
Author(s):  
Michael H. Gelb ◽  
C. Ronald Scott ◽  
Frantisek Turecek ◽  
Hsuan-Chieh Liao
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Tandem Mass

scholarly journals Taiwan National Newborn Screening Program by Tandem Mass Spectrometry for Mucopolysaccharidoses Types I, II, and VI

2019 ◽  
Vol 205 ◽  
pp. 176-182 ◽  
Author(s):  
Min-Ju Chan ◽  
Hsuan-Chieh Liao ◽  
Michael H. Gelb ◽  
Chih-Kuang Chuang ◽  
Mei-Ying Liu ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Screening Program ◽  
Tandem Mass ◽  
Newborn Screening Program

scholarly journals The inclusion of ADA-SCID in expanded newborn screening by tandem mass spectrometry

2014 ◽  
Vol 88 ◽  
pp. 201-206 ◽  
Author(s):  
Giancarlo la Marca ◽  
Elisa Giocaliere ◽  
Sabrina Malvagia ◽  
Silvia Funghini ◽  
Daniela Ombrone ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Tandem Mass ◽  
Expanded Newborn Screening

scholarly journals An Easily Overlooked Contamination of Syringes in Newborn Screening by Tandem Mass Spectrometry

2021 ◽  
Vol 8 ◽  
Author(s):  
Yanyun Wang ◽  
Yun Sun ◽  
Tao Jiang
Keyword(s):  
Mass Spectrometry ◽  
Quality Control ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Retrospective Analysis ◽  
Tandem Mass ◽  
Patient Sample ◽  
Important Test ◽  
Control Samples

Background: Tandem mass spectrometry becomes a common and important test in newborn screening, but potential contamination of the equipment has largely been ignored.Methods: The source of contamination through Biosan quality control samples was examined prospectively, and further confirmed by retrospective analysis of patient samples.Results: We found that the source of contamination came from a syringe in the Biosan quality control samples. Furthermore, we found that a large number of indicators in the patient sample were interfered by syringe contamination in our center, and also in two other newborn screening centers, but the affected indicators were different in different screening centers.Conclusion: Syringe contamination will affect the detection of patient samples by tandem mass spectrometry and should be monitored carefully and immediately.

scholarly journals National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Follow-Up Testing for Metabolic Disease Identified by Expanded Newborn Screening Using Tandem Mass Spectrometry; Executive Summary

2009 ◽  
Vol 55 (9) ◽  
pp. 1615-1626 ◽  
Author(s):  
Dennis J Dietzen ◽  
Piero Rinaldo ◽  
Ronald J Whitley ◽  
William J Rhead ◽  
W Harry Hannon ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Amino Acids ◽  
Tandem Mass Spectrometry ◽  
Organic Acids ◽  
Newborn Screening ◽  
Tandem Mass ◽  
Confirmatory Testing ◽  
The Us ◽  
The Impact

Abstract Background: Almost all newborns in the US are screened at birth for multiple inborn errors of metabolism using tandem mass spectrometry. Screening tests are designed to be sufficiently sensitive so that cases are not missed. The NACB recognized a need for standard guidelines for laboratory confirmation of a positive newborn screen such that all babies would benefit from equal and optimal follow-up by confirmatory testing. Methods: A committee was formed to review available data pertaining to confirmatory testing. The committee evaluated previously published guidelines, published methodological and clinical studies, clinical case reports, and expert opinion to support optimal confirmatory testing. Grading was based on guidelines adopted from criteria derived from the US Preventive Services Task Force and on the strength of recommendations and the quality of the evidence. Three primary methods of analyte measurement were evaluated for confirmatory testing including measurement of amino acids, organic acids, and carnitine esters. The committee graded the evidence for diagnostic utility of each test for the screened conditions. Results: Ample data and experience were available to make strong recommendations for the practice of analyzing amino acids, organic acids, and acylcarnitines. Likewise, strong recommendations were made for the follow-up test menu for many disorders, particularly those with highest prevalence. Fewer data exist to determine the impact of newborn screening on patient outcomes in all but a few disorders. The guidelines also provide an assessment of developing technology that will fuel a refinement of current practice and ultimate expansion of the diseases detectable by tandem mass spectrometry. Conclusions: Guidelines are provided for optimal follow-up testing for positive newborn screens using tandem mass spectrometry. The committee regards these tests as reliable and currently optimal for follow-up testing. .

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