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| Verfasst von: | Brennenstuhl, Heiko [VerfasserIn]  |
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| | Kohlmüller, Dirk [VerfasserIn] |
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| | Gramer, Gwendolyn [VerfasserIn] |
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| | Garbade, Sven [VerfasserIn] |
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| | Syrbe, Steffen [VerfasserIn] |
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| | Feyh, Patrik [VerfasserIn] |
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| | Kölker, Stefan [VerfasserIn] |
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| | Okun, Jürgen G. [VerfasserIn] |
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| | Hoffmann, Georg F. [VerfasserIn] |
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| | Opladen, Thomas [VerfasserIn] |
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| Titel: | High throughput newborn screening for aromatic ʟ-amino-acid decarboxylase deficiency by analysis of concentrations of 3-O-methyldopa from dried blood spots |
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| Verf.angabe: | Heiko Brennenstuhl, Dirk Kohlmüller, Gwendolyn Gramer, Sven F. Garbade, Steffen Syrbe, Patrik Feyh, Stefan Kölker, Jürgen G. Okun, Georg F. Hoffmann, Thomas Opladen |
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| Jahr: | 2020 |
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| Jahr des Originals: | 2019 |
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| Umfang: | 9 S. |
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| Fussnoten: | First published: 18 December 2019 ; Gesehen am 04.06.2020 |
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| Titel Quelle: | Enthalten in: Journal of inherited metabolic disease |
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| Ort Quelle: | Hoboken, NJ : Wiley, 1978 |
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| Jahr Quelle: | 2020 |
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| Band/Heft Quelle: | 43(2020), 3, Seite 602-610 |
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| ISSN Quelle: | 1573-2665 |
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| Abstract: | Aromatic l-amino-acid decarboxylase (AADC) deficiency is an inherited disorder of biogenic amine metabolism with a broad neurological phenotype. The clinical symptoms overlap with other diseases resulting in an often delayed diagnosis. Innovative disease-changing treatment options, particularly gene therapy, have emphasised the need for an early diagnosis. We describe the first method for 3-O-methyldopa (3-OMD) analysis in dried blood spots (DBS) suitable for high throughput newborn screening (NBS). We established a novel tandem mass spectrometry method to quantify 3-OMD in DBS and successfully tested it in 38 888 unaffected newborns, 14 heterozygous DDC variant carriers, seven known AADC deficient patients, and 1079 healthy control subjects. 3-OMD concentrations in 38 888 healthy newborns revealed a mean of 1.16 μmol/L (SD = 0.31, range 0.31-4.6 μmol/L). 1079 non-AADC control subjects (0-18 years) showed a mean 3-OMD concentration of 0.78 μmol/L (SD = 1.75, range 0.24-2.36 μmol/L) with a negative correlation with age. Inter- and intra-assay variability was low, and 3-OMD was stable over 32 days under different storage conditions. We identified seven confirmed AADC deficient patients (mean 3-OMD 9.88 μmol/L [SD = 13.42, range 1.82-36.93 μmol/L]). The highest concentration of 3-OMD was found in a NBS filter card of a confirmed AADC deficient patient with a mean 3-OMD of 35.95 μmol/L. 14 DDC variant carriers showed normal 3-OMD concentrations. We demonstrate a novel high-throughput method to measure 3-OMD in DBS, which allows integration in existing NBS programs enabling early diagnosis of AADC deficiency. |
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| DOI: | doi:10.1002/jimd.12208 |
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| URL: | kostenfrei: Volltext ; Verlag: https://doi.org/10.1002/jimd.12208 |
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| | kostenfrei: Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/jimd.12208 |
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| | DOI: https://doi.org/10.1002/jimd.12208 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | 3-O-methyldopa |
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| | AADC deficiency |
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| | dried blood spot |
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| | newborn screening |
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| | tandem mass spectrometry |
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| K10plus-PPN: | 1699766436 |
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| Verknüpfungen: | → Zeitschrift |
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| Lokale URL UB: |  Zum Volltext |
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High throughput newborn screening for aromatic ʟ-amino-acid decarboxylase deficiency by analysis of concentrations of 3-O-methyldopa from dried blood spots / Brennenstuhl, Heiko [VerfasserIn]; 2020 (Online-Ressource)
