. 2023;10(1):55-65.

doi: 10.3233/JND-221577.

Newbornscreening SMA - From Pilot Project to Nationwide Screening in Germany

Wolfgang Müller-Felber¹, Astrid Blaschek¹, Oliver Schwartz², Dieter Gläser³, Uta Nennstiel⁴, Inken Brockow⁴, Brunhilde Wirth⁵, Siegfried Burggraf⁶, Wulf Röschinger⁶, Marc Becker⁶, Jürgen Durner^{6

7}, Katja Eggermann⁸, Heike Kölbel⁹, Christine Müller¹, Iris Hannibal¹, Bernd Olgemöller¹⁰, Ulrike Schara⁹, Arpad von Moers¹¹, Regina Trollmann¹², Jessika Johannssen¹³, Andreas Ziegler¹⁴, Sebahattin Cirak¹⁵, Andreas Hahn¹⁶, Maja von der Hagen¹⁷, Claudia Weiss¹⁸, Gudrun Schreiber¹⁹, Marina Flotats-Bastardas²⁰, Hans Hartmann²¹, Sabine Illsinger²¹, Astrid Pechmann²², Veronka Horber²³, Jan Kirschner²², Cornelia Köhler²⁴, Benedikt Winter²⁵, Johannes Friese²⁶, Katharina Vill¹

Affiliations

¹ Dr. v. Hauner Children's Hospital, Department of Pediatric Neurology and Developmental Medicine, LMU - University of Munich, Munich, Germany.
² Department of Pediatric Neurology, Muenster University Hospital, Münster, Germany.
³ MVZ Genetikum GmbH, Center for Human Genetics, Neu-Ulm, Germany.
⁴ Screening Center of the Bavarian Health and Food Safety Authority, Oberschleissheim, Germany.
⁵ Institute of Human Genetics, Center for Molecular Genetics Cologne and Center for Rare Diseases Cologne, University of Cologne, Cologne, Germany.
⁶ Labor Becker und Kollegen, Munich, Germany.
⁷ Department of Operative/Restorative Dentistry, Periodontology and Pedodontics, Ludwig-Maximilians-Universität München, Munich, Germany.
⁸ Institute of Human Genetics, Medical Faculty, RWTH Aachen University, Aachen, Germany.
⁹ Department of Pediatric Neurology, Developmental Neurology and Social Pediatrics, University of Essen, Germany.
¹⁰ Formerly Labor Becker, Olgemöller und Kollegen, Munich, Germany.
¹¹ Klinik für Kinder- und Jugendmedizin, Neuropädiatrie, DRK Klinikum Westend, Berlin, Germany.
¹² Department of Pediatrics, Division of Pediatric Neurology, Friedrich-Alexander University ofErlangen-Nürnberg, Erlangen, Germany.
¹³ University Medical Center Hamburg-Eppendorf, Department of Pediatrics, Hamburg, Germany.
¹⁴ Division of Child Neurology and Metabolic Medicine, Center for Child and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany.
¹⁵ Department of Pediatrics, Ulm University, Ulm, Germany.
¹⁶ Department of Child Neurology, University Hospital, Gießen, Germany.
¹⁷ Abteilung Neuropädiatrie, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
¹⁸ Department of Pediatric Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
¹⁹ Department of Pediatric Neurology, Klinikum Kassel, Kassel, Germany.
²⁰ Department of Pediatric Neurology, University Hospital Homburg, Homburg, Germany.
²¹ Hannover Medical School, Clinic for Pediatric Kidney-, Liver- and Metabolic Diseases, OE, Hannover, Germany.
²² Department of Neuropediatrics and Muscle Disorders, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
²³ Department of Paediatric Neurology, University Children's Hospital, Tübingen, Germany.
²⁴ Department of Pediatric Neurology, University of Bochum, Bochum, Germany.
²⁵ Department of Paediatric Neurology, University hospital Mannheim, Mannheim, Germany.
²⁶ Department of Paediatric Neurology, University hospital Bonn, Bonn, Germany.

PMID: 36463459
PMCID: PMC9881029
DOI: 10.3233/JND-221577

Newbornscreening SMA - From Pilot Project to Nationwide Screening in Germany

Wolfgang Müller-Felber et al. J Neuromuscul Dis. 2023.

. 2023;10(1):55-65.

doi: 10.3233/JND-221577.

Authors

Affiliations

¹ Dr. v. Hauner Children's Hospital, Department of Pediatric Neurology and Developmental Medicine, LMU - University of Munich, Munich, Germany.
² Department of Pediatric Neurology, Muenster University Hospital, Münster, Germany.
³ MVZ Genetikum GmbH, Center for Human Genetics, Neu-Ulm, Germany.
⁴ Screening Center of the Bavarian Health and Food Safety Authority, Oberschleissheim, Germany.
⁵ Institute of Human Genetics, Center for Molecular Genetics Cologne and Center for Rare Diseases Cologne, University of Cologne, Cologne, Germany.
⁶ Labor Becker und Kollegen, Munich, Germany.
⁷ Department of Operative/Restorative Dentistry, Periodontology and Pedodontics, Ludwig-Maximilians-Universität München, Munich, Germany.
⁸ Institute of Human Genetics, Medical Faculty, RWTH Aachen University, Aachen, Germany.
⁹ Department of Pediatric Neurology, Developmental Neurology and Social Pediatrics, University of Essen, Germany.
¹⁰ Formerly Labor Becker, Olgemöller und Kollegen, Munich, Germany.
¹¹ Klinik für Kinder- und Jugendmedizin, Neuropädiatrie, DRK Klinikum Westend, Berlin, Germany.
¹² Department of Pediatrics, Division of Pediatric Neurology, Friedrich-Alexander University ofErlangen-Nürnberg, Erlangen, Germany.
¹³ University Medical Center Hamburg-Eppendorf, Department of Pediatrics, Hamburg, Germany.
¹⁴ Division of Child Neurology and Metabolic Medicine, Center for Child and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany.
¹⁵ Department of Pediatrics, Ulm University, Ulm, Germany.
¹⁶ Department of Child Neurology, University Hospital, Gießen, Germany.
¹⁷ Abteilung Neuropädiatrie, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
¹⁸ Department of Pediatric Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
¹⁹ Department of Pediatric Neurology, Klinikum Kassel, Kassel, Germany.
²⁰ Department of Pediatric Neurology, University Hospital Homburg, Homburg, Germany.
²¹ Hannover Medical School, Clinic for Pediatric Kidney-, Liver- and Metabolic Diseases, OE, Hannover, Germany.
²² Department of Neuropediatrics and Muscle Disorders, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
²³ Department of Paediatric Neurology, University Children's Hospital, Tübingen, Germany.
²⁴ Department of Pediatric Neurology, University of Bochum, Bochum, Germany.
²⁵ Department of Paediatric Neurology, University hospital Mannheim, Mannheim, Germany.
²⁶ Department of Paediatric Neurology, University hospital Bonn, Bonn, Germany.

PMID: 36463459
PMCID: PMC9881029
DOI: 10.3233/JND-221577

Abstract

Now that targeted therapies for spinal muscular atrophy are available, attempts are being made worldwide to include screening for spinal muscular atrophy in general newborn screening. In Germany, after pilot projects from 2018-2021, it was included in the general newborn screening from October 2021. To ensure a smooth transition, criteria for follow-up were developed together with key stakeholders. At the beginning of the transition to nationwide screening, false positive findings were reported in 3 patients. After optimization of the screening method in the laboratories concerned, all findings have been subsequently confirmed. On average, the first presentation to a neuromuscular center occurred on day 12 of life, and in patients with 2 or 3 SMN2 copies, therapy started on day 26 of life. Compared with the pilot project, there was no significant delay in timing.

Keywords: 5q-SMA; SMA treatment; Spinal muscular atrophy; newborn screening.

PubMed Disclaimer

Conflict of interest statement

Becker, M.: owner of a commercial entitiy (Labor Becker, Munich, Germany)

Blaschek, A.: speaker honorarium Roche

Brockow, I.: nothing to declare

Burggraf, S.: nothing to declare

Cirak, S.: scientific advisory board Novartis gene therapy

Durner, J.: nothing to declare

Eggermann, K.: nothing to declare

Flotats-Bastardas, M.: scientific advisory board for Biogen, Avexis, Roche. Travel expenses from Biogen. Speaker fees from Avexis.

Friese J: scientific advisory board Novartis gene therapy

Gläser, D.: nothing to declare

Hagen,v.d. M.: member of a scientific advisory board for Avexis, Biogen, Novartis, Pfizer, Roche and Sarepta and received travel expenses and speaker fees from Biogen, Avexis, PTC, Pfizer, Roche, Sarepta

Hahn, A.: scientific advisory board for Biogen, Novartis Gene therapies and speaker fees from Biogen, Novartis Gene Therapies, PTC and Sanofi-Aventis

Hannibal, I.: nothing to declare

Hartmann, H.: nothing to declare

Horber, V-: participated in workshops and received compensation for advisory boards from Novartis and Biogen

Illsinger, S.: scientific Advisory board Novartis

Johannssen, J.: scientific advisory board participation and/or lectures and/or manuscript writing from Avexis/Novartis, Biogen, Roche, PTC, Pfizer and Sarepta

Kirschner, J.: Received honoraria for consultancy/educational activities and clinical research from Biogen, Novartis, Roche and ScholarRock.

Köhler, C.: honoraria for lectures from PTC, Biogen, Roche, Sanofi-Genzyme

Kölbel, H.: scientific advisory board for Novartis and received travel expenses and speaker fees from Biogen and Sanofi-Aventis

Moers von, A.: nothing to declare

Müller, Ch.: nothing to declare

Müller-Felber, W.: scientific advisory board for Biogen, Novartis, PTC, Sarepta, Sanofi-Aventis, Roche and received travel expenses and speaker fees from Biogen, Novartis, PTC, Roche, Sarepta and Sanofi-Aventis

Nennstiel, U.: nothing to declare

Olgemöller, B.: nothing to declare

Pechmann, A.: advisory boards and training activities, and research grants from Novartis and Biogen

Röschinger, W.: nothing to declare

Schara, U.: scientific advisory board Novartis, Roche and Biogen

Schreiber, G.: speaker fees from Novartis

Schwartz, O.: scientific advisory board for Avexis and received travel expenses and speaker fees from Biogen

Trollmann, R.: scientific advisory board for PTC and Biogen. Speaker fees from Biogen, Novartis, PTC.

Vill, K.: speaker fees from Biogen.

Weiss, C.: Personal and/or institutional fees for Advisory Boards and presentations from Novartis, Roche and Biogen

Winter, B.: Speaker fees and Advisory Boards from Novartis, Biogen and Roche

Wirth, B.: received travel expenses and speaker fees from Biogen and Avexis/Novartis

Ziegler, A.: scientific advisory board for Biogen, Avexis, PTC, Sarepta, Novartis Gene Therapies, Roche and Pfizer and received travel expenses and speaker fees from Biogen, Avexis, Novartis Gene Therapies, PTC, Roche, Sarepta and Pfizer

References

1. Wilson JMGJG. Principles and practice of screening for disease. World Health Organisation Public Health Papers. 1968;34.
1. Wirth B. Spinal muscular atrophy: In the challenge lies a solution. Trends Neurosci. 2021. - PubMed
1. Calucho M, Bernal S, Alias L, et al.. Correlation between SMA type and SMN2 copy number revisited: An analysis of 625 unrelated Spanish patients and a compilation of reported cases. Neuromuscular Disorders: NMD. 2018;28:208–15. - PubMed
1. Feldkotter M, Schwarzer V, Wirth R, Wienker TF, Wirth B. Quantitative analyses of SMN1 and SMN2 based on real-time lightCycler PCR: Fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy. American Journal of Human Genetics. 2002;70:358–68. - PMC - PubMed
1. Mendell JR, Al-Zaidy S, Shell R, et al.. Single-dose gene-replacement therapy for spinal muscular atrophy. The New England Journal of Medicine. 2017;377:1713–22. - PubMed

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Newbornscreening SMA - From Pilot Project to Nationwide Screening in Germany

Affiliations

Newbornscreening SMA - From Pilot Project to Nationwide Screening in Germany

Authors

Affiliations

Abstract

Conflict of interest statement

References

MeSH terms

LinkOut - more resources

Full Text Sources

Medical