Three years pilot of spinal muscular atrophy newborn screening turned into official program in Southern Belgium

François Boemer¹, Jean-Hubert Caberg², Pablo Beckers³, Vinciane Dideberg², Samantha di Fiore³, Vincent Bours⁴, Sandrine Marie⁵, Joseph Dewulf⁵, Lionel Marcelis⁶, Nicolas Deconinck⁷, Aurore Daron⁸, Laura Blasco-Perez⁹, Eduardo Tizzano⁹, Mickaël Hiligsmann¹⁰, Jacques Lombet¹¹, Tatiana Pereira¹¹, Lucia Lopez-Granados¹¹, Sarvnaz Shalchian-Tehran¹², Véronique van Assche¹³, Arabelle Willems¹³, Sofie Huybrechts¹⁴, Bénédicte Mast¹⁵, Rudolf van Olden¹⁶, Tamara Dangouloff⁸, Laurent Servais^{8

17}

Affiliations

¹ Biochemical Genetics Laboratory, Human Genetics, CHU Sart-Tilman, University of Liège, B35, 4000, Liège, Belgium. F.Boemer@chuliege.be.
² Molecular Genetics Lab, Department of Human Genetics, CHU of Liège, University of Liège, Liège, Belgium.
³ Biochemical Genetics Laboratory, Human Genetics, CHU Sart-Tilman, University of Liège, B35, 4000, Liège, Belgium.
⁴ Department of Human Genetics, CHU of Liège, University of Liège, Liège, Belgium.
⁵ Department of Laboratory Medicine, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, Belgium.
⁶ Laboratory of Pediatric Research, Free University of Brussels, Brussels, Belgium.
⁷ Neuromuscular Reference Center, Hôpital des Enfants Reine Fabiola (HUDERF), Université Libre de Bruxelles, Brussels, Belgium.
⁸ Division of Child Neurology, Reference Center for Neuromuscular Diseases, Department of Pediatrics, CHR Citadelle, University of Liège, Liège, Belgium.
⁹ Department of Clinical and Molecular Genetics, Hospital Valle Hebron, Barcelona, Spain.
¹⁰ Department of Health Services Research, CAPHRI Care and Public Health Research Institute, Maastricht University, Maastricht, The Netherlands.
¹¹ ONE, Office de la Naissance et de l'Enfance, Herstal, Belgium.
¹² Department of Neurology and Ethic Committee, CHR Citadelle, Liège, Belgium.
¹³ ABMM, Association Belge contre les Maladies neuro-Musculaires ASBL, La Louvière, Belgium.
¹⁴ Biogen, Cambridge, MA, USA.
¹⁵ Roche, Basel, Switzerland.
¹⁶ Novartis Gene Therapies Switzerland GmBH, Zürich, Switzerland.
¹⁷ MDUK Neuromuscular Center, Department of Paediatrics, University of Oxford, Oxford, UK.

PMID: 34620959
PMCID: PMC8497564
DOI: 10.1038/s41598-021-99496-2

Three years pilot of spinal muscular atrophy newborn screening turned into official program in Southern Belgium

François Boemer et al. Sci Rep. 2021.

. 2021 Oct 7;11(1):19922.

doi: 10.1038/s41598-021-99496-2.

Authors

Affiliations

¹ Biochemical Genetics Laboratory, Human Genetics, CHU Sart-Tilman, University of Liège, B35, 4000, Liège, Belgium. F.Boemer@chuliege.be.
² Molecular Genetics Lab, Department of Human Genetics, CHU of Liège, University of Liège, Liège, Belgium.
³ Biochemical Genetics Laboratory, Human Genetics, CHU Sart-Tilman, University of Liège, B35, 4000, Liège, Belgium.
⁴ Department of Human Genetics, CHU of Liège, University of Liège, Liège, Belgium.
⁵ Department of Laboratory Medicine, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, Belgium.
⁶ Laboratory of Pediatric Research, Free University of Brussels, Brussels, Belgium.
⁷ Neuromuscular Reference Center, Hôpital des Enfants Reine Fabiola (HUDERF), Université Libre de Bruxelles, Brussels, Belgium.
⁸ Division of Child Neurology, Reference Center for Neuromuscular Diseases, Department of Pediatrics, CHR Citadelle, University of Liège, Liège, Belgium.
⁹ Department of Clinical and Molecular Genetics, Hospital Valle Hebron, Barcelona, Spain.
¹⁰ Department of Health Services Research, CAPHRI Care and Public Health Research Institute, Maastricht University, Maastricht, The Netherlands.
¹¹ ONE, Office de la Naissance et de l'Enfance, Herstal, Belgium.
¹² Department of Neurology and Ethic Committee, CHR Citadelle, Liège, Belgium.
¹³ ABMM, Association Belge contre les Maladies neuro-Musculaires ASBL, La Louvière, Belgium.
¹⁴ Biogen, Cambridge, MA, USA.
¹⁵ Roche, Basel, Switzerland.
¹⁶ Novartis Gene Therapies Switzerland GmBH, Zürich, Switzerland.
¹⁷ MDUK Neuromuscular Center, Department of Paediatrics, University of Oxford, Oxford, UK.

PMID: 34620959
PMCID: PMC8497564
DOI: 10.1038/s41598-021-99496-2

Abstract

Three new therapies for spinal muscular atrophy (SMA) have been approved by the United States Food and Drug Administration and the European Medicines Agency since 2016. Although these new therapies improve the quality of life of patients who are symptomatic at first treatment, administration before the onset of symptoms is significantly more effective. As a consequence, newborn screening programs have been initiated in several countries. In 2018, we launched a 3-year pilot program to screen newborns for SMA in the Belgian region of Liège. This program was rapidly expanding to all of Southern Belgium, a region of approximately 55,000 births annually. During the pilot program, 136,339 neonates were tested for deletion of exon 7 of SMN1, the most common cause of SMA. Nine SMA cases with homozygous deletion were identified through this screen. Another patient was identified after presenting with symptoms and was shown to be heterozygous for the SMN1 exon 7 deletion and a point mutation on the opposite allele. These ten patients were treated. The pilot program has now successfully transitioned into the official neonatal screening program in Southern Belgium. The lessons learned during implementation of this pilot program are reported.

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Conflict of interest statement

L.S. is member of Biogen, AveXis, Roche, and Cytokinetics scientific advisory boards and has provided consultancy to Roche, AveXis, and Biogen. E.T. has received grant support to conduct clinical trials on SMA from Ionis/Biogen and serves as a consultant to AveXis, Novartis, Biogen, Biologix, Cytokinetics, Roche. A.D. is investigator of SMA studies for Roche and Novartis Gene Therapies and received honoraria for consultancy for the scientific advisory board of AveXis Belgium. B.M. is an employee of Roche. S.H. is an employee of and has stock/stock options in Biogen. R.V.O. is employee of Novartis Gene Therapies and owns Novartis stock or other equities. T.D. and F.B. have given lectures sponsored by Biogen, Novartis and Roche. The other authors have no financial disclosures relevant to this article.

Figures

**Figure 1**
TAT improvement over the study period.

**Figure 2**
Box-and-whisker plot of the endpoint-fluorescence *SMN1* to *RPP30* ratio for negative (n = 136.330) and positive (n = 9) screening results.

**Figure 3**
Screening and diagnostic flowchart.

See this image and copyright information in PMC

References

1. Lefebvre S, et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell. 1995;80:155–165. doi: 10.1016/0092-8674(95)90460-3. - DOI - PubMed
1. Kolb SJ, et al. Natural history of infantile-onset spinal muscular atrophy. Ann. Neurol. 2017;82:883–891. doi: 10.1002/ana.25101. - DOI - PMC - PubMed
1. Ramdas S, Servais L. New treatments in spinal muscular atrophy: An overview of currently available data. Expert Opin. Pharmacother. 2020;21:307–315. doi: 10.1080/14656566.2019.1704732. - DOI - PubMed
1. Finkel RS, et al. Nusinersen versus sham control in infantile-onset spinal muscular atrophy. N. Engl. J. Med. 2017;377:1723–1732. doi: 10.1056/NEJMoa1702752. - DOI - PubMed
1. Mendell JR, et al. Single-dose gene-replacement therapy for spinal muscular atrophy. N. Engl. J. Med. 2017;377:1713–1722. doi: 10.1056/NEJMoa1706198. - DOI - PubMed

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Three years pilot of spinal muscular atrophy newborn screening turned into official program in Southern Belgium

Affiliations

Three years pilot of spinal muscular atrophy newborn screening turned into official program in Southern Belgium

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

Medical

Research Materials