Genomic Analysis of Historical Cases with Positive Newborn Screens for Short-Chain Acyl-CoA Dehydrogenase Deficiency Shows That a Validated Second-Tier Biochemical Test Can Replace Future Sequencing
Short-chain acyl-CoA dehydrogenase deficiency (SCADD) is a rare autosomal recessive disorder of β-oxidation caused by pathogenic variants in the ACADS gene. Analyte testing for SCADD in blood and urine, including newborn screening (NBS) using tandem mass spectrometry (MS/MS) on dried blood spots (DBSs), is complicated by the presence of two relatively common ACADS variants (c.625G>A and c.511C>T). Individuals homozygous for these variants or compound heterozygous do not have clinical disease but do have reduced short-chain acyl-CoA dehydrogenase (SCAD) activity, resulting in elevated blood and urine metabolites. As part of a larger study of the potential role of exome sequencing in NBS in California, we reviewed ACADS sequence and MS/MS data from DBSs from a cohort of 74 patients identified to have SCADD. Of this cohort, approximately 60% had one or more of the common variants and did not have the two rare variants, and thus would need no further testing. Retrospective analysis of ethylmalonic acid, glutaric acid, 2-hydroxyglutaric acid, 3-hydroxyglutaric acid, and methylsuccinic acid demonstrated that second-tier testing applied before the release of the newborn screening result could reduce referrals by over 50% and improve the positive predictive value for SCADD to above 75%.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:6 |
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| Enthalten in: |
International journal of neonatal screening - 6(2020), 2 vom: 25. Juni |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Adhikari, Aashish N [VerfasserIn] |
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| Links: |
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| Themen: |
ACADS |
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| Anmerkungen: |
Date Revised 28.09.2020 published: Print-Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3390/ijns6020041 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM313775990 |
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| 245 | 1 | 0 | |a Genomic Analysis of Historical Cases with Positive Newborn Screens for Short-Chain Acyl-CoA Dehydrogenase Deficiency Shows That a Validated Second-Tier Biochemical Test Can Replace Future Sequencing |
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| 520 | |a Short-chain acyl-CoA dehydrogenase deficiency (SCADD) is a rare autosomal recessive disorder of β-oxidation caused by pathogenic variants in the ACADS gene. Analyte testing for SCADD in blood and urine, including newborn screening (NBS) using tandem mass spectrometry (MS/MS) on dried blood spots (DBSs), is complicated by the presence of two relatively common ACADS variants (c.625G>A and c.511C>T). Individuals homozygous for these variants or compound heterozygous do not have clinical disease but do have reduced short-chain acyl-CoA dehydrogenase (SCAD) activity, resulting in elevated blood and urine metabolites. As part of a larger study of the potential role of exome sequencing in NBS in California, we reviewed ACADS sequence and MS/MS data from DBSs from a cohort of 74 patients identified to have SCADD. Of this cohort, approximately 60% had one or more of the common variants and did not have the two rare variants, and thus would need no further testing. Retrospective analysis of ethylmalonic acid, glutaric acid, 2-hydroxyglutaric acid, 3-hydroxyglutaric acid, and methylsuccinic acid demonstrated that second-tier testing applied before the release of the newborn screening result could reduce referrals by over 50% and improve the positive predictive value for SCADD to above 75% | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Currier, Robert J |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Turgeon, Coleman T |e verfasserin |4 aut | |
| 700 | 1 | |a Nussbaum, Robert L |e verfasserin |4 aut | |
| 700 | 1 | |a Srinivasan, Rajgopal |e verfasserin |4 aut | |
| 700 | 1 | |a Sunderam, Uma |e verfasserin |4 aut | |
| 700 | 1 | |a Kwok, Pui-Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Brenner, Steven E |e verfasserin |4 aut | |
| 700 | 1 | |a Gavrilov, Dimitar |e verfasserin |4 aut | |
| 700 | 1 | |a Puck, Jennifer M |e verfasserin |4 aut | |
| 700 | 1 | |a Gallagher, Renata |e verfasserin |4 aut | |
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