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

Publikation

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

Wissenschaftlicher Artikel/Review - 27.02.2024

Vill Katharina, Tacke Moritz, König Anna, Baumann Matthias, Baumgartner Manuela, Steinbach Meike, Bernert Günther, Blaschek Astrid, Deschauer Marcus, Flotats-Bastardas Marina, Friese Johannes, Goldbach Susanne, Gross Martin, Günther René, Hahn Andreas, Hagenacker Tim, Hauser Erwin, Horber Veronka, Illsinger Sabine, Johannsen Jessika, Kamm Christoph, Koch Jan Christoph, Kölbel Heike, Köhler Cornelia, Kolzter Kirsten, Lochmüller Hanns, Ludolph Albert C, Mensch Alexander, Meyer Zu Hoerste Gerd, Mueller Monika, Mueller-Felber Wolfgang, Neuwirth Christoph, Petri Susanne, Probst-Schendzielorz Kristina, Pühringer Manuel, Steinbach Robert, Schara-Schmidt Ulrike, Schimmel Mareike, Schrank Bertold, Schwartz Oliver, Schlachter Kurt, Schwerin-Nagel Annette, Schreiber Gudrun, Smitka Martin, Topakian Raffi, Trollmann Regina, Türk Matthias, Theophil Manuela, Rauscher Christian, Vorgerd Mathias, Walter M C, Weiler Markus, Weiss Claudia, Wilichowski Ekkehard, Wurster Claudia D, Wunderlich Gilbert, Zeller Daniel, Ziegler Andreas, Kirschner Janbernd, Pechmann Astrid, SMArtCARE study group

Zitation

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 J, Kölbel H, Köhler 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 M, Weiler M, Weiss C, Wilichowski E, Wurster C, Wunderlich G, Zeller D, Ziegler A, Kirschner J, Pechmann A, SMArtCARE study group. 5qSMA: standardised retrospective natural history assessment in 268 patients with four copies of SMN2. J Neurol 2024

Art

Wissenschaftlicher Artikel/Review (Englisch)

Zeitschrift

J Neurol 2024

Veröffentlichungsdatum

27.02.2024

eISSN (Online)

1432-1459

Kurzbeschreibung/Zielsetzung

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.