scholarly journals Newborn Screening for Isovaleric Acidemia Using Tandem Mass Spectrometry: Data from 1.6 Million Newborns

2011 ◽  
Vol 57 (4) ◽  
pp. 623-626 ◽  
Author(s):  
Regina Ensenauer ◽  
Ralph Fingerhut ◽  
Esther M Maier ◽  
Roman Polanetz ◽  
Bernhard Olgemöller ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Positive Predictive Value ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Predictive Value ◽  
Recall Rate ◽  
Tandem Mass ◽  
Esi Ms ◽  
Isovaleric Acidemia ◽  
Threshold Criteria

BACKGROUND Electrospray ionization–tandem mass spectrometry (ESI-MS/MS) has been used in the Bavarian newborn screening (NBS) program since 1999. The use of ESI-MS/MS has led to the inclusion of isovaleric acidemia (IVA) into NBS. We retrospectively evaluated data on more than 1.6 million newborns screened during 9.5 years. METHODS Acylcarnitines from whole blood spotted on filter paper were converted to their corresponding butyl esters, and the samples were analyzed by use of ESI-MS/MS with stable isotope labeled internal standards. RESULTS A total of 24 individuals with IVA were detected by use of a multiparametric threshold criteria panel including isovalerylcarnitine (C5) and the ratios of C5 to octanoyl-, butyryl-, and propionylcarnitine. A cutoff set at the 99.99th percentile for isolated C5 or at the 99th percentile for C5 plus at least 2 ratios resulted in a positive predictive value for IVA screening of 7.0% and an overall recall rate of 0.024%. Adjusted reference ranges for age and birth weight were applied, and the incidence of IVA in the study population was calculated to be 1 in 67 000. Missed cases were not brought to our attention. IVA was also detectable in cord blood and early postnatal blood samples. CONCLUSIONS IVA can be reliably detected in NBS through acylcarnitine analysis in dried blood spots by using multiparametric threshold criteria. Further improvement (positive predictive value 13.0%, recall rate 0.01%) can be achieved by using more stringent recall criteria. In view of the potentially life-threatening natural course of IVA in early life, presymptomatic diagnosis may thus prevent mortality and morbidity.

Direct sequencing of a disulfide-linked peptide with electrospray ionization tandem mass spectrometry

The Analyst ◽  
2015 ◽  
Vol 140 (8) ◽  
pp. 2623-2627 ◽  
Author(s):  
Gongyu Li ◽  
Jiying Pei ◽  
Yue Yin ◽  
Guangming Huang
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Corona Discharge ◽  
Electrospray Ionization ◽  
Disulfide Bonds ◽  
Direct Sequencing ◽  
Peptide Sequencing ◽  
Tandem Mass ◽  
Esi Ms ◽  
Ionization Tandem Mass Spectrometry

Enhanced corona discharge was employed for in-spray dissociation of disulfide bonds, facilitating disulfide-containing peptide sequencing with ESI-MS/MS.

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
Sign in / Sign up

Export Citation Format

Share Document