Neonatal diagnosis of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency and implications for newborn screening by tandem mass spectrometry

1999 ◽  
Vol 22 (7) ◽  
pp. 840-841 ◽  
Author(s):  
K. H. Carpenter ◽  
B. Wilcken
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Dehydrogenase Deficiency ◽  
Tandem Mass ◽  
Neonatal Diagnosis ◽  
Hydroxyacyl Coa Dehydrogenase ◽  
Long Chain

Very Long-Chain Acyl-CoA Dehydrogenase Deficiency in a Patient with Normal Newborn Screening by Tandem Mass Spectrometry

2010 ◽  
Vol 156 (3) ◽  
pp. 492-494 ◽  
Author(s):  
Can Ficicioglu ◽  
Curtis R. Coughlin ◽  
Michael J. Bennett ◽  
Marc Yudkoff
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Dehydrogenase Deficiency ◽  
Tandem Mass ◽  
Chain Acyl ◽  
Long Chain

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 Newborn Screening for Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase and Mitochondrial Trifunctional Protein Deficiencies Using Acylcarnitines Measurement in Dried Blood Spots—A Systematic Review of Test Accuracy

2021 ◽  
Vol 9 ◽  
Author(s):  
Chris Stinton ◽  
Hannah Fraser ◽  
Julia Geppert ◽  
Rebecca Johnson ◽  
Martin Connock ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Dried Blood Spots ◽  
Test Accuracy ◽  
Tandem Mass ◽  
Blood Spots ◽  
Hydroxyacyl Coa Dehydrogenase ◽  
Sensitivity Specificity ◽  
Long Chain

Background: Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and mitochondrial trifunctional protein (MTP) deficiencies are rare autosomal recessive fatty acid β-oxidation disorders. Their clinical presentations are variable, and premature death is common. They are included in newborn blood spot screening programs in many countries around the world. The current process of screening, through the measurement of acylcarnitines (a metabolic by-product) in dried blood spots with tandem mass spectrometry, is subject to uncertainty regarding test accuracy.Methods: We conducted a systematic review of literature published up to 19th June 2018. We included studies that investigated newborn screening for LCHAD or MTP deficiencies by tandem mass spectrometry of acylcarnitines in dried blood spots. The reference standards were urine organic acids, blood acylcarnitine profiles, enzyme analysis in cultured fibroblasts or lymphocytes, mutation analysis, or at least 10-year follow-up. The outcomes of interest were sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Assessment of titles, abstracts, and full-text papers and quality appraisal were carried out independently by two reviewers. One reviewer extracted study data. This was checked by a second reviewer.Results: Ten studies provided data on test accuracy. LCHAD or MTP deficiencies were identified in 23 babies. No cases of LCHAD/MTP deficiencies were identified in four studies. PPV ranged from 0% (zero true positives and 28 false positives from 276,565 babies screened) to 100% (13 true positives and zero false positives from 2,037,824 babies screened). Sensitivity, specificity, and NPV could not be calculated as there was no systematic follow-up of babies who screened negative.Conclusions: Test accuracy estimates of screening for LCHAD and MTP deficiencies with tandem mass spectrometry measurement of acylcarnitines in dried blood were variable in terms of PPVs. Screening methods (including markers and thresholds) varied between studies, and sensitivity, specificity, and NPVs are unknown.

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.

Tandem Mass Spectrometry Screening for Very Long-Chain Acyl-CoA Dehydrogenase Deficiency: The Value of Second-Tier Enzyme Testing

2010 ◽  
Vol 157 (4) ◽  
pp. 668-673 ◽  
Author(s):  
Ute Spiekerkoetter ◽  
Ulrike Haussmann ◽  
Martina Mueller ◽  
Frank ter Veld ◽  
Maren Stehn ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Dehydrogenase Deficiency ◽  
Tandem Mass ◽  
Chain Acyl ◽  
Second Tier ◽  
Long Chain

Newborn Screening by Tandem Mass Spectrometry for Medium-Chain Acyl-CoA Dehydrogenase Deficiency: A Cost-Effectiveness Analysis

PEDIATRICS ◽  
2003 ◽  
Vol 112 (5) ◽  
pp. 1005-1015 ◽  
Author(s):  
L. N. Venditti ◽  
C. P. Venditti ◽  
G. T. Berry ◽  
P. B. Kaplan ◽  
E. M. Kaye ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cost Effectiveness ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Dehydrogenase Deficiency ◽  
Cost Effectiveness Analysis ◽  
Tandem Mass ◽  
Medium Chain ◽  
Effectiveness Analysis ◽  
Chain Acyl

Prospective Diagnosis of 2-Methylbutyryl-CoA Dehydrogenase Deficiency in the Hmong Population by Newborn Screening Using Tandem Mass Spectrometry

PEDIATRICS ◽  
2003 ◽  
Vol 112 (1) ◽  
pp. 74-78 ◽  
Author(s):  
D. Matern ◽  
M. He ◽  
S. A. Berry ◽  
P. Rinaldo ◽  
C. B. Whitley ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Dehydrogenase Deficiency ◽  
Tandem Mass
Sign in / Sign up

Export Citation Format

Share Document