Newborn Screen for X-Linked Adrenoleukodystrophy Using Flow Injection Tandem Mass Spectrometry in Negative Ion Mode
X-linked adrenoleukodystrophy (X-ALD) is a genetic disorder caused by pathogenic variants in the ATP-binding cassette subfamily D member 1 gene (<i>ABCD1</i>) that encodes the adrenoleukodystrophy protein (ALDP). Defects in ALDP result in elevated cerotic acid, and lead to C26:0-lysophos...
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| Format: | Article |
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MDPI AG
2022-04-01
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| Series: | International Journal of Neonatal Screening |
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| Online Access: | https://www.mdpi.com/2409-515X/8/2/27 |
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| author | Tarek A. Teber Brian J. Conti Christopher A. Haynes Amy Hietala Mei W. Baker |
| author_facet | Tarek A. Teber Brian J. Conti Christopher A. Haynes Amy Hietala Mei W. Baker |
| author_sort | Tarek A. Teber |
| collection | DOAJ |
| description | X-linked adrenoleukodystrophy (X-ALD) is a genetic disorder caused by pathogenic variants in the ATP-binding cassette subfamily D member 1 gene (<i>ABCD1</i>) that encodes the adrenoleukodystrophy protein (ALDP). Defects in ALDP result in elevated cerotic acid, and lead to C26:0-lysophosphatidylcholine (C26:0-LPC) accumulation, which is the primary biomarker used in newborn screening (NBS) for X-ALD. C26:0-LPC levels were measured in dried blood spot (DBS) NBS specimens using a flow injection analysis (FIA) coupled with electrospray ionization (ESI) tandem mass spectrometry (MS/MS) performed in negative ion mode. The method was validated by assessing and confirming linearity, accuracy, and precision. We have also established C26:0-LPC cutoff values that identify newborns at risk for X-ALD. The mean concentration of C26:0-LPC in 5881 de-identified residual routine NBS specimens was 0.07 ± 0.02 µM (mean + 1 standard deviation (SD)). All tested true X-ALD positive and negative samples were correctly identified based on C26:0-LPC cutoff concentrations for borderline between 0.15 µM and 0.22 µM (mean + 4 SD) and presumptive screening positive at ≥0.23 µM (mean + 8 SD). The presented FIA method shortens analysis run-time to 1.7 min, while maintaining the previously established advantage of utilizing negative mode MS to eliminate isobaric interferences that could lead to screening false positives. |
| first_indexed | 2024-03-09T23:31:21Z |
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| id | doaj.art-9b7413b1e7ad4961b066919bca11b546 |
| institution | Directory Open Access Journal |
| issn | 2409-515X |
| language | English |
| last_indexed | 2024-03-09T23:31:21Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
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| series | International Journal of Neonatal Screening |
| spelling | doaj.art-9b7413b1e7ad4961b066919bca11b5462023-11-23T17:08:29ZengMDPI AGInternational Journal of Neonatal Screening2409-515X2022-04-01822710.3390/ijns8020027Newborn Screen for X-Linked Adrenoleukodystrophy Using Flow Injection Tandem Mass Spectrometry in Negative Ion ModeTarek A. Teber0Brian J. Conti1Christopher A. Haynes2Amy Hietala3Mei W. Baker4Newborn Screening Laboratory, Wisconsin State Laboratory of Hygiene, University of Wisconsin School of Medicine and Public Health, 465 Henry Mall, Madison, WI 53706, USANewborn Screening Laboratory, Wisconsin State Laboratory of Hygiene, University of Wisconsin School of Medicine and Public Health, 465 Henry Mall, Madison, WI 53706, USANewborn Screening and Molecular Biology Branch, Centers for Disease Control and Prevention, 4770 Buford Hwy. NE, Atlanta, GA 30341, USANewborn Screening Laboratory, Minnesota Department of Health, St. Paul, MN 55164, USANewborn Screening Laboratory, Wisconsin State Laboratory of Hygiene, University of Wisconsin School of Medicine and Public Health, 465 Henry Mall, Madison, WI 53706, USAX-linked adrenoleukodystrophy (X-ALD) is a genetic disorder caused by pathogenic variants in the ATP-binding cassette subfamily D member 1 gene (<i>ABCD1</i>) that encodes the adrenoleukodystrophy protein (ALDP). Defects in ALDP result in elevated cerotic acid, and lead to C26:0-lysophosphatidylcholine (C26:0-LPC) accumulation, which is the primary biomarker used in newborn screening (NBS) for X-ALD. C26:0-LPC levels were measured in dried blood spot (DBS) NBS specimens using a flow injection analysis (FIA) coupled with electrospray ionization (ESI) tandem mass spectrometry (MS/MS) performed in negative ion mode. The method was validated by assessing and confirming linearity, accuracy, and precision. We have also established C26:0-LPC cutoff values that identify newborns at risk for X-ALD. The mean concentration of C26:0-LPC in 5881 de-identified residual routine NBS specimens was 0.07 ± 0.02 µM (mean + 1 standard deviation (SD)). All tested true X-ALD positive and negative samples were correctly identified based on C26:0-LPC cutoff concentrations for borderline between 0.15 µM and 0.22 µM (mean + 4 SD) and presumptive screening positive at ≥0.23 µM (mean + 8 SD). The presented FIA method shortens analysis run-time to 1.7 min, while maintaining the previously established advantage of utilizing negative mode MS to eliminate isobaric interferences that could lead to screening false positives.https://www.mdpi.com/2409-515X/8/2/27dried blood spotsflow injection analysisC26:0-lysophosphatidylcholinenewborn screeningtandem mass spectrometryX-linked adrenoleukodystrophy |
| spellingShingle | Tarek A. Teber Brian J. Conti Christopher A. Haynes Amy Hietala Mei W. Baker Newborn Screen for X-Linked Adrenoleukodystrophy Using Flow Injection Tandem Mass Spectrometry in Negative Ion Mode International Journal of Neonatal Screening dried blood spots flow injection analysis C26:0-lysophosphatidylcholine newborn screening tandem mass spectrometry X-linked adrenoleukodystrophy |
| title | Newborn Screen for X-Linked Adrenoleukodystrophy Using Flow Injection Tandem Mass Spectrometry in Negative Ion Mode |
| title_full | Newborn Screen for X-Linked Adrenoleukodystrophy Using Flow Injection Tandem Mass Spectrometry in Negative Ion Mode |
| title_fullStr | Newborn Screen for X-Linked Adrenoleukodystrophy Using Flow Injection Tandem Mass Spectrometry in Negative Ion Mode |
| title_full_unstemmed | Newborn Screen for X-Linked Adrenoleukodystrophy Using Flow Injection Tandem Mass Spectrometry in Negative Ion Mode |
| title_short | Newborn Screen for X-Linked Adrenoleukodystrophy Using Flow Injection Tandem Mass Spectrometry in Negative Ion Mode |
| title_sort | newborn screen for x linked adrenoleukodystrophy using flow injection tandem mass spectrometry in negative ion mode |
| topic | dried blood spots flow injection analysis C26:0-lysophosphatidylcholine newborn screening tandem mass spectrometry X-linked adrenoleukodystrophy |
| url | https://www.mdpi.com/2409-515X/8/2/27 |
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