Butyrylcarnitine Elevation in Newborn Screening: Reducing False Positives and Distinguishing between Two Rare Diseases through the Evaluation of New Ratios
One of the main challenges of newborn screening programs, which screen for inherited metabolic disorders, is cutting down on false positives (FPs) in order to avoid family stresses, additional analyses, and unnecessary costs. False positives are partly caused by an insubstantial number of robust bio...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/12/3247 |
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| author | MariaAnna Messina Alessia Arena Riccardo Iacobacci Luisa La Spina Concetta Meli Federica Raudino Martino Ruggieri |
| author_facet | MariaAnna Messina Alessia Arena Riccardo Iacobacci Luisa La Spina Concetta Meli Federica Raudino Martino Ruggieri |
| author_sort | MariaAnna Messina |
| collection | DOAJ |
| description | One of the main challenges of newborn screening programs, which screen for inherited metabolic disorders, is cutting down on false positives (FPs) in order to avoid family stresses, additional analyses, and unnecessary costs. False positives are partly caused by an insubstantial number of robust biomarkers in evaluations. Another challenge is how to distinguish between diseases which share the same primary marker and for which secondary biomarkers are just as highly desirable. Focusing on pathologies that involve butyrylcarnitine (C4) elevation, such as short-chain acylCoA dehydrogenase deficiency (SCADD) and isobutyrylCoA dehydrogenase deficiency (IBDD), we investigated the acylcarnitine profile of 121 newborns with a C4 increase to discover secondary markers to achieve two goals: reduce the FP rate and discriminate between the two rare diseases. Analyses were carried out using tandem mass spectrometry with whole blood samples spotted on filter paper. Seven new biomarkers (C4/C0, C4/C5, C4/C5DC\C6OH, C4/C6, C4/C8, C4/C14:1, C4/C16:1) were identified using a non-parametric ANOVA analysis. Then, the corresponding cut-off values were found and applied to the screening program. The seven new ratios were shown to be robust (<i>p</i> < 0.001 and <i>p</i> < 0.01, 0.0937 < ε<sup>2</sup> < 0.231) in discriminating between FP and IBDD patients, FP and SCADD patients, or SCADD and IBDD patients. Our results suggest that the new ratios are optimal indicators for identifying true positives, distinguishing between two rare diseases that share the same primary biomarker, improving the predictive positive value (PPV) and reducing the false positive rate (FPR). |
| first_indexed | 2024-03-08T20:58:47Z |
| format | Article |
| id | doaj.art-9126cde2554c48b684ae16cfe6f0c7e4 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-08T20:58:47Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-9126cde2554c48b684ae16cfe6f0c7e42023-12-22T13:55:05ZengMDPI AGBiomedicines2227-90592023-12-011112324710.3390/biomedicines11123247Butyrylcarnitine Elevation in Newborn Screening: Reducing False Positives and Distinguishing between Two Rare Diseases through the Evaluation of New RatiosMariaAnna Messina0Alessia Arena1Riccardo Iacobacci2Luisa La Spina3Concetta Meli4Federica Raudino5Martino Ruggieri6Expanded Newborn Screening Laboratory, Newborn Screening and Metabolic Diseases Unit, University-Polyclinic “G. Rodolico-San Marco”, 95123 Catania, ItalyExpanded Newborn Screening Laboratory, Newborn Screening and Metabolic Diseases Unit, University-Polyclinic “G. Rodolico-San Marco”, 95123 Catania, ItalyExpanded Newborn Screening Laboratory, Newborn Screening and Metabolic Diseases Unit, University-Polyclinic “G. Rodolico-San Marco”, 95123 Catania, ItalyExpanded Newborn Screening Laboratory, Newborn Screening and Metabolic Diseases Unit, University-Polyclinic “G. Rodolico-San Marco”, 95123 Catania, ItalyExpanded Newborn Screening Laboratory, Newborn Screening and Metabolic Diseases Unit, University-Polyclinic “G. Rodolico-San Marco”, 95123 Catania, ItalyExpanded Newborn Screening Laboratory, Newborn Screening and Metabolic Diseases Unit, University-Polyclinic “G. Rodolico-San Marco”, 95123 Catania, ItalyExpanded Newborn Screening Laboratory, Newborn Screening and Metabolic Diseases Unit, University-Polyclinic “G. Rodolico-San Marco”, 95123 Catania, ItalyOne of the main challenges of newborn screening programs, which screen for inherited metabolic disorders, is cutting down on false positives (FPs) in order to avoid family stresses, additional analyses, and unnecessary costs. False positives are partly caused by an insubstantial number of robust biomarkers in evaluations. Another challenge is how to distinguish between diseases which share the same primary marker and for which secondary biomarkers are just as highly desirable. Focusing on pathologies that involve butyrylcarnitine (C4) elevation, such as short-chain acylCoA dehydrogenase deficiency (SCADD) and isobutyrylCoA dehydrogenase deficiency (IBDD), we investigated the acylcarnitine profile of 121 newborns with a C4 increase to discover secondary markers to achieve two goals: reduce the FP rate and discriminate between the two rare diseases. Analyses were carried out using tandem mass spectrometry with whole blood samples spotted on filter paper. Seven new biomarkers (C4/C0, C4/C5, C4/C5DC\C6OH, C4/C6, C4/C8, C4/C14:1, C4/C16:1) were identified using a non-parametric ANOVA analysis. Then, the corresponding cut-off values were found and applied to the screening program. The seven new ratios were shown to be robust (<i>p</i> < 0.001 and <i>p</i> < 0.01, 0.0937 < ε<sup>2</sup> < 0.231) in discriminating between FP and IBDD patients, FP and SCADD patients, or SCADD and IBDD patients. Our results suggest that the new ratios are optimal indicators for identifying true positives, distinguishing between two rare diseases that share the same primary biomarker, improving the predictive positive value (PPV) and reducing the false positive rate (FPR).https://www.mdpi.com/2227-9059/11/12/3247inherited disordersnewborn screeningtandem mass spectrometrybiomarkers |
| spellingShingle | MariaAnna Messina Alessia Arena Riccardo Iacobacci Luisa La Spina Concetta Meli Federica Raudino Martino Ruggieri Butyrylcarnitine Elevation in Newborn Screening: Reducing False Positives and Distinguishing between Two Rare Diseases through the Evaluation of New Ratios Biomedicines inherited disorders newborn screening tandem mass spectrometry biomarkers |
| title | Butyrylcarnitine Elevation in Newborn Screening: Reducing False Positives and Distinguishing between Two Rare Diseases through the Evaluation of New Ratios |
| title_full | Butyrylcarnitine Elevation in Newborn Screening: Reducing False Positives and Distinguishing between Two Rare Diseases through the Evaluation of New Ratios |
| title_fullStr | Butyrylcarnitine Elevation in Newborn Screening: Reducing False Positives and Distinguishing between Two Rare Diseases through the Evaluation of New Ratios |
| title_full_unstemmed | Butyrylcarnitine Elevation in Newborn Screening: Reducing False Positives and Distinguishing between Two Rare Diseases through the Evaluation of New Ratios |
| title_short | Butyrylcarnitine Elevation in Newborn Screening: Reducing False Positives and Distinguishing between Two Rare Diseases through the Evaluation of New Ratios |
| title_sort | butyrylcarnitine elevation in newborn screening reducing false positives and distinguishing between two rare diseases through the evaluation of new ratios |
| topic | inherited disorders newborn screening tandem mass spectrometry biomarkers |
| url | https://www.mdpi.com/2227-9059/11/12/3247 |
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