The Clinical Impact of CLIR Tools toward Rapid Resolution of Post-Newborn Screening Confirmatory Testing for X-Linked Adrenoleukodystrophy in California
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 (<i>ABCD1</i>) gene variant of uncertain significance (VUS). To determine retrospectively the like...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-08-01
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| Series: | International Journal of Neonatal Screening |
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| Online Access: | https://www.mdpi.com/2409-515X/6/3/62 |
| _version_ | 1797560214238527488 |
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| author | Hao Tang Jamie Matteson Piero Rinaldo Silvia Tortorelli Robert Currier Stanley Sciortino |
| author_facet | Hao Tang Jamie Matteson Piero Rinaldo Silvia Tortorelli Robert Currier Stanley Sciortino |
| author_sort | Hao Tang |
| collection | DOAJ |
| description | 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 (<i>ABCD1</i>) 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 <i>ABCD1</i> 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 <i>ABCD1</i> 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. |
| first_indexed | 2024-03-10T17:56:17Z |
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| institution | Directory Open Access Journal |
| issn | 2409-515X |
| language | English |
| last_indexed | 2024-03-10T17:56:17Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Neonatal Screening |
| spelling | doaj.art-aaa90dbba1e8455f98433542b2eac03b2023-11-20T09:10:56ZengMDPI AGInternational Journal of Neonatal Screening2409-515X2020-08-01636210.3390/ijns6030062The Clinical Impact of CLIR Tools toward Rapid Resolution of Post-Newborn Screening Confirmatory Testing for X-Linked Adrenoleukodystrophy in CaliforniaHao Tang0Jamie Matteson1Piero Rinaldo2Silvia Tortorelli3Robert Currier4Stanley Sciortino5Genetic Disease Screening Program, California Department of Public Health, Richmond, CA 94804, USAGenetic Disease Screening Program, California Department of Public Health, Richmond, CA 94804, USABiochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USABiochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USADepartment of Pediatrics, University of California, San Francisco, CA 94158, USAGenetic Disease Screening Program, California Department of Public Health, Richmond, CA 94804, USASince 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 (<i>ABCD1</i>) 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 <i>ABCD1</i> 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 <i>ABCD1</i> 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.https://www.mdpi.com/2409-515X/6/3/62newborn screeningX-linked adrenoleukodystrophyvery long-chain fatty-acidsATP binding cassette subfamily D member 1variants of uncertain significanceconfirmatory test |
| spellingShingle | Hao Tang Jamie Matteson Piero Rinaldo Silvia Tortorelli Robert Currier Stanley Sciortino The Clinical Impact of CLIR Tools toward Rapid Resolution of Post-Newborn Screening Confirmatory Testing for X-Linked Adrenoleukodystrophy in California International Journal of Neonatal Screening newborn screening X-linked adrenoleukodystrophy very long-chain fatty-acids ATP binding cassette subfamily D member 1 variants of uncertain significance confirmatory test |
| title | The Clinical Impact of CLIR Tools toward Rapid Resolution of Post-Newborn Screening Confirmatory Testing for X-Linked Adrenoleukodystrophy in California |
| title_full | The Clinical Impact of CLIR Tools toward Rapid Resolution of Post-Newborn Screening Confirmatory Testing for X-Linked Adrenoleukodystrophy in California |
| title_fullStr | The Clinical Impact of CLIR Tools toward Rapid Resolution of Post-Newborn Screening Confirmatory Testing for X-Linked Adrenoleukodystrophy in California |
| title_full_unstemmed | The Clinical Impact of CLIR Tools toward Rapid Resolution of Post-Newborn Screening Confirmatory Testing for X-Linked Adrenoleukodystrophy in California |
| title_short | The Clinical Impact of CLIR Tools toward Rapid Resolution of Post-Newborn Screening Confirmatory Testing for X-Linked Adrenoleukodystrophy in California |
| title_sort | clinical impact of clir tools toward rapid resolution of post newborn screening confirmatory testing for x linked adrenoleukodystrophy in california |
| topic | newborn screening X-linked adrenoleukodystrophy very long-chain fatty-acids ATP binding cassette subfamily D member 1 variants of uncertain significance confirmatory test |
| url | https://www.mdpi.com/2409-515X/6/3/62 |
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