{"doi":"10.1001/jamanetworkopen.2019.20356","title":"Evaluation of X-Linked Adrenoleukodystrophy Newborn Screening in North Carolina","abstract":"Importance: X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal genetic disorder in which an accumulation of very long-chain fatty acids leads to inflammatory demyelination in the central nervous system and to adrenal cortex atrophy. In 2016, X-ALD was added to the US Recommended Uniform Screening Panel. Objective: To evaluate the performance of a single-tier newborn screening assay for X-ALD in North Carolina. Design, Setting, and Participants: This diagnostic screening study was of all newborn dried blood spot specimens received in the North Carolina State Laboratory of Public Health between January 2 and June 1, 2018, excluding specimens of insufficient quantity or quality. A total of 52 301 specimens were screened for X-ALD using negative ionization high-performance liquid chromatography tandem mass spectrometry to measure C24:0- and C26:0-lysophosphatidylcholine concentrations. Sanger sequencing of the adenosine triphosphate-binding cassette subfamily D member 1 (ABCD1) gene was performed on screen-positive specimens. Exposures: A medical and family history, newborn physical examination, sequencing of ABCD1 on dried blood spot samples, and plasma analysis of very long-chain fatty acids were obtained for all infants with screen-positive results. Main Outcomes and Measures: The prevalence of X-ALD in North Carolina and the positive predictive value and false-positive rate for the first-tier assay were determined. Results: Of 52 301 infants tested (47.8% female, 50.6% male, and 1.7% other or unknown sex), 12 received screen-positive results. Of these 12 infants, 8 were confirmed with a genetic disorder: 3 male infants with X-ALD, 3 X-ALD-heterozygous female infants, 1 female infant with a peroxisome biogenesis disorder, and 1 female infant with Aicardi-Goutières syndrome. Four infants were initially classified as having false-positives results, including 3 female infants who were deemed unaffected and 1 male infant with indeterminate results on confirmatory testing. The positive predictive value for X-ALD or other genetic disorders for the first-tier assay was 67%, with a false-positive rate of 0.0057%. Conclusions and Relevance: This newborn screening pilot study reported results on 2 lysophosphatidylcholine analytes, identifying 3 male infants with X-ALD, 3 X-ALD-heterozygous female infants, and 3 infants with other disorders associated with increased very long-chain fatty acids. These results showed successful implementation in a public health program with minimal risk to the population. The findings will support other state laboratories planning to implement newborn screening for X-ALD and related disorders.","journal":"JAMA Network Open","year":2020,"id":59552,"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":66,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9473,"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":315828,"name":"Kristin Clinard","orcid":null,"position":1,"is_corresponding":false},{"id":313809,"name":"Sarah P. Young","orcid":"0000-0002-7671-016X","position":2,"is_corresponding":false},{"id":313810,"name":"Catherine Rehder","orcid":"0000-0003-4924-9010","position":3,"is_corresponding":false},{"id":313811,"name":"Zheng Fan","orcid":"0000-0003-1934-2521","position":4,"is_corresponding":false},{"id":315829,"name":"Ali S. Çalıkoğlu","orcid":null,"position":5,"is_corresponding":false},{"id":313812,"name":"Deeksha Bali","orcid":"0000-0003-2550-8073","position":6,"is_corresponding":false},{"id":313813,"name":"Donald B. Bailey","orcid":"0000-0002-0513-9330","position":7,"is_corresponding":false},{"id":313814,"name":"Lisa M. Gehtland","orcid":"0000-0002-4475-9268","position":8,"is_corresponding":false},{"id":315830,"name":"David S. Millington","orcid":null,"position":9,"is_corresponding":false},{"id":315831,"name":"Hari S. Patel","orcid":null,"position":10,"is_corresponding":false},{"id":315832,"name":"Sara E. Beckloff","orcid":null,"position":11,"is_corresponding":false},{"id":315833,"name":"Scott J. Zimmerman","orcid":null,"position":12,"is_corresponding":false},{"id":313815,"name":"Cynthia M. Powell","orcid":"0000-0002-4260-5601","position":13,"is_corresponding":false},{"id":313816,"name":"Jennifer Taylor","orcid":"0000-0001-6942-1696","position":14,"is_corresponding":false},{"id":313808,"name":"Stacey Lee","orcid":"0000-0003-0691-0032","position":0,"is_corresponding":true}],"reference_count":27,"raw_metadata":null,"created_at":"2026-07-18T21:08:26.834549Z","pmid":"32003821","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":[]}