5qSMA: standardised retrospective natural history assessment in 268 patients with four copies of SMN2

Vill K, Tacke M, König A, Baumann M, Baumgartner M, Steinbach M, Bernert G, Blaschek A, Deschauer M, Flotats-Bastardas M, Friese J, Goldbach S, Gross M, Günther R, Hahn A, Hagenacker T, Hauser E, Horber V, Illsinger S, Johannsen J, Kamm C, Koch JC, Koelbel H, Koehler C, Kolzter K, Lochmüller H, Ludolph A, Mensch A, Meyer zu Hoerste G, Mueller M, Mueller-Felber W, Neuwirth C, Petri S, Probst-Schendzielorz K, Pühringer M, Steinbach R, Schara-Schmidt U, Schimmel M, Schrank B, Schwartz O, Schlachter K, Schwerin-Nagel A, Schreiber G, Smitka M, Topakian R, Trollmann R, Türk M, Theophil M, Rauscher C, Vorgerd M, Walter MC, Weiler M, Weiss C, Wilichowski E, Wurster CD, Wunderlich G, Zeller D, Ziegler A, Kirschner J, Pechmann A (2024)

Publication Type: Journal article

Publication year: 2024

Journal

DOI: 10.1007/s00415-024-12188-5

Abstract

Newborn screening for 5qSMA offers the potential for early, ideally pre-symptomatic, therapeutic intervention. However, limited data exist on the outcomes of individuals with 4 copies of SMN2, and there is no consensus within the SMA treatment community regarding early treatment initiation in this subgroup. To provide evidence-based insights into disease progression, we performed a retrospective analysis of 268 patients with 4 copies of SMN2 from the SMArtCARE registry in Germany, Austria and Switzerland. Inclusion criteria required comprehensive baseline data and diagnosis outside of newborn screening. Only data prior to initiation of disease-modifying treatment were included. The median age at disease onset was 3.0 years, with a mean of 6.4 years. Significantly, 55% of patients experienced symptoms before the age of 36 months. 3% never learned to sit unaided, a further 13% never gained the ability to walk independently and 33% of ambulatory patients lost this ability during the course of the disease. 43% developed scoliosis, 6.3% required non-invasive ventilation and 1.1% required tube feeding. In conclusion, our study, in line with previous observations, highlights the substantial phenotypic heterogeneity in SMA. Importantly, this study provides novel insights: the median age of disease onset in patients with 4 SMN2 copies typically occurs before school age, and in half of the patients even before the age of three years. These findings support a proactive approach, particularly early treatment initiation, in this subset of SMA patients diagnosed pre-symptomatically. However, it is important to recognize that the register will not include asymptomatic individuals.

Authors with CRIS profile

Involved external institutions

Klinikum Wels-Grieskirchen Austria (AT) Universitätsklinikum Heidelberg Germany (DE) Julius-Maximilians-Universität Würzburg Germany (DE) Initiative „Forschung und Therapie für die Spinale Muskelatrophie“ im Förderverein für die Deutsche Gesellschaft für Muskelkranke e.V. (Initiative SMA) Germany (DE) Katholisches Klinikum Bochum (St. Josef- und St. Elisabeth-Hospital gGmbH) Germany (DE) Universität Duisburg-Essen (UDE) Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) Germany (DE) Universitätsklinikum Ulm Germany (DE) Klinikum Kassel GmbH Germany (DE) Universitätsklinikum Bonn Germany (DE) Medizinische Universität Innsbruck Austria (AT) Universitätsklinikum Tübingen Germany (DE) Georg-August-Universität Göttingen Germany (DE) Deutsche Gesellschaft für Muskelkranke (DGM) Germany (DE) HELIOS Kliniken Germany (DE) Universitätsklinikum Jena Germany (DE) Universitätsklinikum Göttingen Germany (DE) Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Germany (DE) Klinikum der Universität München (LMU Klinikum) Germany (DE) Kepler Universitätsklinikum (KUK) Austria (AT) Universitätsklinikum Würzburg Germany (DE) Universität Salzburg (Paris Lodron Universität Salzburg) Austria (AT) Universität Rostock Germany (DE) Universitätsklinikum Carl Gustav Carus Dresden Germany (DE) Medizinische Universität Graz Austria (AT) Landeskrankenhaus Bregenz Austria (AT) Universitätsklinikum Essen Germany (DE) Universität Ulm Germany (DE) Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil Germany (DE) Ordensklinikum Linz GmbH Barmherzige Schwestern Austria (AT) Universitätsklinikum Augsburg Germany (DE) Universitätsklinikum des Saarlandes (UKS) Germany (DE) Charité - Universitätsmedizin Berlin Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Kliniken der Stadt Köln Germany (DE) Klinikum rechts der Isar Germany (DE) Universitätsklinikum Halle (Saale) Germany (DE) Justus-Liebig-Universität Gießen Germany (DE) DRK-Kliniken Berlin Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Children's Hospital of Eastern Ontario (CHEO) / Centre hospitalier pour enfants de l'est de l'Ontario Canada (CA) Kantonsspital St.Gallen Switzerland (CH) Evangelisches Krankenhaus Oldenburg Germany (DE) Universitätsklinikum Münster Germany (DE)

How to cite

APA:

Vill, K., Tacke, M., König, A., Baumann, M., Baumgartner, M., Steinbach, M.,... Pechmann, A. (2024). 5qSMA: standardised retrospective natural history assessment in 268 patients with four copies of SMN2. Journal of Neurology. https://doi.org/10.1007/s00415-024-12188-5

MLA:

Vill, Katharina, et al. "5qSMA: standardised retrospective natural history assessment in 268 patients with four copies of SMN2." Journal of Neurology (2024).

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