Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Mar 31;16(1):153.
doi: 10.1186/s13023-021-01783-8.

Newborn screening for spinal muscular atrophy in Germany: clinical results after 2 years

Katharina Vill #  1 , Oliver Schwartz #  2 , Astrid Blaschek  1 , Dieter Gläser  3 , Uta Nennstiel  4 , Brunhilde Wirth  5 , Siegfried Burggraf  6 , Wulf Röschinger  6 , Marc Becker  6 , Ludwig Czibere  6 , Jürgen Durner  6   7 , Katja Eggermann  8 , Bernhard Olgemöller  9 , Erik Harms  10 , Ulrike Schara  11 , Heike Kölbel #  11 , Wolfgang Müller-Felber #  12
Affiliations

Newborn screening for spinal muscular atrophy in Germany: clinical results after 2 years

Katharina Vill et al. Orphanet J Rare Dis. .

Abstract

Background: Spinal muscular atrophy (SMA) is the most common neurodegenerative disease in childhood. Since motor neuron injury is usually not reversible, early diagnosis and treatment are essential to prevent major disability. Our objective was to assess the impact of genetic newborn screening for SMA on outcome.

Methods: We provided clinical data from 43 SMA patients, identified via polymerase chain reaction of the SMN1 gene from dried blood spots between January 2018 and January 2020 in Germany. Follow-up included neurophysiological examinations and standardized physiotherapeutic testing.

Results: Detection of SMA with newborn screening was consistent with known incidence in Germany. Birth prevalence was 1:6910; 39.5% had 2 SMN2 copies, 23% had 3 SMN2 copies, 32.5% had 4 copies, and 4.5% had 5 copies of the SMN2 gene. Treatment with SMA-specific medication could be started at the age of 14-39 days in 21 patients. Pre-symptomatically treated patients remained throughout asymptomatic within the observation period. 47% of patients with 2 SMN2 copies showed early, presumably intrauterine onset of disease. These patients reached motor milestones with delay; none of them developed respiratory symptoms. Untreated children with 2 SMN2 copies died. Untreated children with 3 SMN2 copies developed proximal weakness in their first year. In patients with ≥ 4 SMN2 copies, a follow-up strategy of "watchful waiting" was applied despite the fact that one of them was treated from the age of 6 months. Two infant siblings with 4 SMN2 copies were identified with a missed diagnosis of SMA type 3.

Conclusion: Identification of newborns with infantile SMA and prompt SMA-specific treatment substantially improves neurodevelopmental outcome, and we recommend implementation in the public newborn screening in countries where therapy is available. Electrophysiology is a relevant parameter to support the urgency of therapy. There has to be a short time interval between a positive screening result and referral to a therapy-ready specialized treatment center.

PubMed Disclaimer

Conflict of interest statement

All authors have indicated that they don’t have any non-financial conflicts of interest. Financial Disclosure: Astrid Blaschek, Bernhard Olgemöller, Erik Harms, Katja Eggermann and Uta Nennstiel have nothing to disclose. Marc Becker is the owner of a commercial entity (Laboratory Becker and colleagues MVZ GbR, Führichstraße 70, 81871 Munich, Germany). Siegfried Burggraf, Wulf Röschinger, Jürgen Durner, Ludwig Czibere are employed at a commercial entity (Laboratory Becker and colleagues MVZ GbR, Führichstraße 70, 81871 Munich, Germany). Dieter Gläser is the co-owner of a commercial entity (Genetikum®, Wegenerstr. 15, 89231 Neu-Ulm, Germany). Katharina Vill has received travel expenses and speaker fees from Biogen. Oliver Schwartz has served as a member of a scientific advisory board for Avexis and received travel expenses and speaker fees from Biogen. Heike Kölbel has served as a member of a scientific advisory board for Avexis and received travel expenses and speaker fees from Biogen and Sanofi-Aventis. Ulrika Schara has served as a member of a scientific advisory board and data safety monitoring board for Biogen, Avexis and Novartis and received speaker fees from Biogen, Avexis, PTC and Sanofi-Aventis. Brunhilde Wirth has served as a member of a scientific advisory board and data safety monitoring board for SMA Europe and received travel expenses and speaker fees from Biogen. Wolfgang Müller-Felber has served as a member of a scientific advisory board for Biogen, Avexis, PTC, Sanofi-Aventis, Roche and Cytokinetics and received travel expenses and speaker fees from Biogen, Avexis, PTC and Sanofi-Aventis.

Figures

Fig. 1
Fig. 1
Course of a HINE-2, b CHOP INTEND and c Ulnar CMAPs with increasing age. n.t. = not treated. * Pat 11, symptomatic age 8 months, treated from the age of 10 months. **Pat 15 and 16, not treated: Further measurements were refused by the parents
Fig. 1
Fig. 1
Course of a HINE-2, b CHOP INTEND and c Ulnar CMAPs with increasing age. n.t. = not treated. * Pat 11, symptomatic age 8 months, treated from the age of 10 months. **Pat 15 and 16, not treated: Further measurements were refused by the parents
Fig. 2
Fig. 2
x-axis: age in months (either at the time of the time reaching the respective milestone or at age of last presentation). y-axis: probability of NOT reaching the milestone. log-rank test: test for equality of the three different curves. The P-value (Log-Rank-Test) < 0.05 indicates that the three curves differ significantly from each other. Solid lines: Result curves. Dashed lines in corresponding colors: confidence interval
See this image and copyright information in PMC

References

    1. Hohenfellner K, Bergmann C, Fleige T, et al. Molecular based newborn screening in Germany: Follow-up for cystinosis. Mol Genet Metab Rep. 2019;21:100514. doi: 10.1016/j.ymgmr.2019.100514. - DOI - PMC - PubMed
    1. Mercuri E, Finkel RS, Muntoni F, et al. Diagnosis and management of spinal muscular atrophy: Part 1: Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care. Neuromuscular disorders : NMD. 2018;28:103–115. doi: 10.1016/j.nmd.2017.11.005. - DOI - PubMed
    1. Wirth B, Karakaya M, Kye MJ, Mendoza-Ferreira N. Twenty-Five Years of Spinal Muscular Atrophy Research: From Phenotype to Genotype to Therapy, and What Comes Next. Annu Rev Genomics Hum Genet 2020. - PubMed
    1. Ramos DM, d'Ydewalle C, Gabbeta V, et al. Age-dependent SMN expression in disease-relevant tissue and implications for SMA treatment. J Clin Investig. 2019;129:4817–4831. doi: 10.1172/JCI124120. - DOI - PMC - PubMed
    1. Konig K, Pechmann A, Thiele S, et al. De-duplicating patient records from three independent data sources reveals the incidence of rare neuromuscular disorders in Germany. Orphanet J Rare Dis. 2019;14:152. doi: 10.1186/s13023-019-1125-2. - DOI - PMC - PubMed

Publication types

Substances