scholarly journals Reference Standards for Newborn Screening of Metabolic Disorders by Tandem Mass Spectrometry: A Nationwide Study on Millions of Chinese Neonatal Populations

2021 ◽  
Vol 8 ◽  
Author(s):  
Falin He ◽  
Rulai Yang ◽  
Xinwen Huang ◽  
Yaping Tian ◽  
Xiaofang Pei ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Clinical Problem ◽  
Reference Intervals ◽  
Tandem Mass ◽  
Nationwide Study ◽  
Disease Biomarkers ◽  
Health And Disease ◽  
Age And Sex

Introduction: The major clinical problem presently confronting the Chinese newborn screening (NBS) programs by tandem mass spectrometry (MS/MS) is the lack of comprehensive reference intervals (RIs) for disease biomarkers. To close this gap, the Chinese National Center for Clinical Laboratories (NCCL) launched a nationwide study to investigate the dynamic pattern of 35 MS/MS NBS biomarkers and establish accurate and robust RIs.Methods: Blood spot samples from 4,714,089 Chinese neonates were tested in participating centers/laboratories and used for study analysis. MS/MS NBS biomarker trends were visually assessed by their concentrations over age. Specific partitions were determined arbitrarily by each day and sex or by the statistical method of Harris and Boyd. RIs, corresponding to the 2.5th and 97.5th percentiles, as well as the 1th, 25th, 75th and 99th percentiles were calculated for each reference partition using a non-parametric rank approach.Results: Most MS/MS NBS biomarkers fluctuated during the first week of life, followed by a relatively stable concentration. Age and sex-specific RIs were established and presented an improved specificity over the RIs used in participating centers/laboratories. Females demonstrated higher 2.5th and 97.5th percentiles in all amino acids except arginine and ornithine than males, whereas males showed higher 2.5th and 97.5th percentiles in most acylcarnitines.Conclusion: The present study determined the dynamic trends of 35 MS/MS biomarkers and established age and sex-specific RIs, valuably contributing to the current literature and timely evaluation of neonatal health and disease.

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. .

scholarly journals Rapid diagnosis of MCAD deficiency: quantitative analysis of octanoylcarnitine and other acylcarnitines in newborn blood spots by tandem mass spectrometry

1997 ◽  
Vol 43 (11) ◽  
pp. 2106-2113 ◽  
Author(s):  
Donald H Chace ◽  
Steven L Hillman ◽  
Johan L K Van Hove ◽  
Edwin W Naylor
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Chain Length ◽  
Filter Paper ◽  
Tandem Mass ◽  
Mcad Deficiency ◽  
Medium Chain ◽  
Blood Spots ◽  
Medium Chain Length

Abstract We report the application of tandem mass spectrometry to prospective newborn screening for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. MCAD deficiency is diagnosed from dried blood spots on filter paper cards from newborns on the basis of the increase of medium chain length acylcarnitines identified by isotope dilution mass spectrometry methods. A robust and accurate semiautomated method for the analysis of medium chain length acylcarnitines as their butyl esters was developed and validated. Quantitative data from the analyses of 113 randomly collected filter paper blood spots from healthy newborns showed low concentrations of medium chain length acylcarnitines such as octanoylcarnitine. The maximum concentration of octanoylcarnitine was 0.22 μmol/L, with the majority being at or below the detection limit. In all 16 blood spots from newborns with confirmed MCAD deficiency, octanoylcarnitine was highly increased [median 8.4 μmol/L (range 3.1–28.3 μmol/L)], allowing easy detection. The concentration of octanoylcarnitine was significantly higher in these 16 newborns (<3 days of age) than in 16 older patients (ages 8 days to 7 years) with MCAD deficiency (median 1.57 μmol/L, range 0.33–4.4). The combined experience of prospective newborn screening in Pennsylvania and North Carolina has shown a disease frequency for MCAD deficiency of 1 in 17 706. No false-positive and no known false-negative results have been found. A validated method now exists for prospective newborn screening for MCAD deficiency.

scholarly journals Neonatal Screening on Tandem Mass Spectrometry as a Powerful Tool for the Reassessment of the Prevalence of Underestimated Diseases in Newborns and Their Family Members: A Focus on Short Chain Acyl-CoA Dehydrogenase Deficiency

2020 ◽  
Vol 6 (3) ◽  
pp. 58
Author(s):  
MariaAnna Messina ◽  
Alessia Arena ◽  
Agata Fiumara ◽  
Riccardo Iacobacci ◽  
Concetta Meli ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Dehydrogenase Deficiency ◽  
Family Members ◽  
Clinical Manifestations ◽  
Vitamin B12 Deficiency ◽  
Short Chain ◽  
Tandem Mass ◽  
Chain Acyl

Early detection of disabling diseases, prior to clinical manifestations, is the primary goal of newborn screening (NS). Indeed, the required number of core and secondary conditions selected for screening panels is increasing in many countries. Furthermore, newborn screening can lead to diagnosis of maternal diseases such as vitamin B12 deficiency or 3-MethylcrotonylCoA-carboxylase deficiency (3MCC). NS became mandatory in Sicily in December 2017. Here we report NS data collected between December 2017 and April 2020. Our results show that tandem mass spectrometry is a powerful tool for discovery of underestimated disease in newborns and their family members. Our panel included short chain acyl-CoA dehydrogenase deficiency (SCADD). Here, we report that results of our investigation led to reassessment of SCADD prevalence in our population. The infant and adult patients diagnosed in our study had previously not shown overt symptoms.

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