{"doi":"10.3390/ijns6020041","title":"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","abstract":"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%.","journal":"International Journal of Neonatal Screening","year":2020,"id":70438,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9468,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":237921,"name":"Robert J. Currier","orcid":"0000-0001-9168-5604","position":1,"is_corresponding":false},{"id":372417,"name":"Hao Tang","orcid":"0000-0001-9409-5220","position":2,"is_corresponding":false},{"id":372418,"name":"Coleman Turgeon","orcid":"0009-0000-9416-9074","position":3,"is_corresponding":false},{"id":2900,"name":"Robert L. Nussbaum","orcid":"0000-0003-3445-8880","position":4,"is_corresponding":false},{"id":239234,"name":"Rajgopal Srinivasan","orcid":null,"position":5,"is_corresponding":false},{"id":239235,"name":"Uma Sunderam","orcid":null,"position":6,"is_corresponding":false},{"id":94249,"name":"Pui–Yan Kwok","orcid":"0000-0002-5087-3059","position":7,"is_corresponding":false},{"id":38052,"name":"Steven E. Brenner","orcid":"0000-0001-7559-6185","position":8,"is_corresponding":false},{"id":372419,"name":"Dimitar Gavrilov","orcid":"0000-0002-8871-2808","position":9,"is_corresponding":false},{"id":237928,"name":"Jennifer M. Puck","orcid":"0000-0001-6623-6276","position":10,"is_corresponding":false},{"id":237919,"name":"Renata C. Gallagher","orcid":"0000-0003-1611-0354","position":11,"is_corresponding":false},{"id":237918,"name":"Aashish N. Adhikari","orcid":"0000-0003-4305-9494","position":0,"is_corresponding":true}],"reference_count":10,"raw_metadata":null,"created_at":"2026-07-18T21:43:11.119231Z","pmid":"32802992","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}