High throughput newborn screening for Sickle cell disease - application of two-tiered testing with a qPCR-based primary screen

• Verfasst von: Janda, Joachim [VerfasserIn]
• Verfasst von: Hegert, Sebastian [VerfasserIn]
• Verfasst von: Bzdok, Jessica [VerfasserIn]
• Verfasst von: Tesorero, Rafael [VerfasserIn]
• Verfasst von: Holtkamp, Ute [VerfasserIn]
• Verfasst von: Burggraf, Siegfried [VerfasserIn]
• Verfasst von: Schuhmann, Elfriede [VerfasserIn]
• Verfasst von: Hörster, Friederike [VerfasserIn]
• Verfasst von: Hoffmann, Georg F. [VerfasserIn]
• Verfasst von: Janzen, Nils [VerfasserIn]
• Verfasst von: Okun, Jürgen G. [VerfasserIn]
• Verfasst von: Becker, Marc [VerfasserIn]
• Verfasst von: Durner, Jürgen [VerfasserIn]
• Titel: High throughput newborn screening for Sickle cell disease - application of two-tiered testing with a qPCR-based primary screen
• Paralleltitel: Hochdurchsatz-Neugeborenenscreening auf Sichelzellkrankheit - Anwendung einer zweistufigen Analytik mit einem qPCR-basierten Primärscreening
• Verf.angabe: Joachim Janda, Sebastian Hegert, Jessica Bzdok, Rafael Tesorero, Ute Holtkamp, Siegfried Burggraf, Elfriede Schuhmann, Friedrike Hörster, Georg F. Hoffmann, Nils Janzen, Jürgen G. Okun, Marc Becker, Jürgen Durner
• Jahr: 2023
• Umfang: 7 S.
• Illustrationen: Illustrationen
• Fussnoten: Artikel online veröffentlicht: 25. September 2023 ; Gesehen am 07.11.2023
• Titel Quelle: Enthalten in: Klinische Pädiatrie
• Ort Quelle: Stuttgart : Thieme, 1972
• Jahr Quelle: 2023
• Band/Heft Quelle: (2023), Seite 1-7
• ISSN Quelle: 0300-8630
• DOI: doi:10.1055/a-2153-7789
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1869528840

Abstract

Background: Sickle cell disease (SCD) is a group of hemoglobinopathies with a common point mutation causing the production of sickle cell hemoglobin (HbS). In high-throughput newborn screening (NBS) for SCD, a two-step procedure is suitable, in which qPCR first pre-selects relevant samples that are differentiated by a second method. Methods: Three NBS centers using qPCR-based primary screening for SCD performed a laboratory comparison. Methods using tandem MS or HPLC were used for differentiation. Results: In a benchmarking test, 450 dried blood samples were analyzed. Samples containing HbS were detected as reliably by qPCR as by methods established for hemoglobinopathy testing. In a two-step screening approach, the 2nd-tier-analyses have to distinguish the carrier status from pathological variants. In nine months of regular screening, a total of 353,219 samples were analyzed using two-stage NBS procedures. The 1st-tier screening by qPCR reduced the number of samples for subsequent differentiation by >99.5%. Cases with carrier status or other variants were identified as inconspicuous while 78 cases with SCD were revealed. The derived incidence of 1:4,773, is in good agreement with previously published incidences. Conclusion: In high-throughput NBS for SCD, qPCR is suitable to focus 2nd-tier analyses on samples containing HbS, while being unaffected by factors such as prematurity or transfusions. The substantial reduction of samples numbers positively impacts resource conservation, sustainability, and cost-effectiveness. No false negative cases came to attention.