The Clinical Impact of CLIR Tools toward Rapid Resolution of Post-Newborn Screening Confirmatory Testing for X-Linked Adrenoleukodystrophy in California
| Autor: | Silvia Tortorelli, Piero Rinaldo, Jamie Matteson, Robert J. Currier, Hao Tang, Stanley Sciortino |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty variants of uncertain significance endocrine system diseases Disease 030105 genetics & heredity Article 03 medical and health sciences 0302 clinical medicine Immunology and Microbiology (miscellaneous) Internal medicine X-linked adrenoleukodystrophy False positive paradox Medicine post-analytical interpretation Newborn screening screening test performance business.industry newborn screening lcsh:RJ1-570 Obstetrics and Gynecology nutritional and metabolic diseases lcsh:Pediatrics Guideline bioinformatics Score interpretation medicine.disease very long-chain fatty-acids ATP binding cassette subfamily D member 1 Pediatrics Perinatology and Child Health confirmatory test Adrenoleukodystrophy business 030217 neurology & neurosurgery |
| Zdroj: | International Journal of Neonatal Screening Volume 6 Issue 3 International Journal of Neonatal Screening, Vol 6, Iss 62, p 62 (2020) |
| ISSN: | 2409-515X |
| DOI: | 10.3390/ijns6030062 |
| Popis: | Since the start of X-linked adrenoleukodystrophy (ALD) newborn screening in California, more than half of the diagnosed cases were found to have an ATP binding cassette subfamily D member 1 (ABCD1) gene variant of uncertain significance (VUS). To determine retrospectively the likelihood that these were true positive cases, we used a web-based post-analytical tool in Collaborative Laboratory Integrated Reports (CLIR). Confirmatory plasma very long-chain fatty-acids (VLCFA) profiles for ALD screen positive infant boys were run through the CLIR ALD tool. We compared the distribution by ABCD1 variant classification (pathogenic, likely pathogenic, VUS, and no variant) with the CLIR tool score interpretation (non-informative, possibly ALD, likely ALD, and very likely ALD) and the current case diagnosis. The study showed that CLIR tool positive interpretations were consistent with 100% of the pathogenic and likely pathogenic variants on the ABCD1 gene if a more conservative guideline was used. The tool interpretations were also consistent with screened cases that were determined to not have disease (our no-disorder group). The CLIR tool identified 19 diagnosed ALD cases with VUS to be potential false positives, representing a 40% reduction among all diagnosed ALD cases with VUS. The reduction could be extended to 65% if a more aggressive threshold was used. Identifying such preventable false positives could alleviate the follow-up burden for patients, their families, and California Special Care Centers. |
| Databáze: | OpenAIRE |
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