% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Vill:269341,
author = {Vill, Katharina and Tacke, Moritz and König, Anna and
Baumann, Matthias and Baumgartner, Manuela and Steinbach,
Meike and Bernert, Guenther and Blaschek, Astrid and
Deschauer, Marcus and Flotats-Bastardas, Marina and Friese,
Johannes and Goldbach, Susanne and Gross, Martin and
Günther, René and Hahn, Andreas and Hagenacker, Tim and
Hauser, Erwin and Horber, Veronka and Illsinger, Sabine and
Johannsen, Jessika and Kamm, Christoph and Koch, Jan C and
Koelbel, Heike and Koehler, Cornelia and Kolzter, Kirsten
and Lochmüller, Hanns and Ludolph, Albert and Mensch,
Alexander and Meyer Zu Hoerste, Gerd and Mueller, Monika and
Mueller-Felber, Wolfgang and Neuwirth, Christoph and Petri,
Susanne and Probst-Schendzielorz, Kristina and Pühringer,
Manuel and Steinbach, Robert and Schara-Schmidt, Ulrike and
Schimmel, Mareike and Schrank, Bertold and Schwartz, Oliver
and Schlachter, Kurt and Schwerin-Nagel, Annette and
Schreiber, Gudrun and Smitka, Martin and Topakian, Raffi and
Trollmann, Regina and Tuerk, Matthias and Theophil, Manuela
and Rauscher, Christian and Vorgerd, Mathias and Walter,
Maggie C and Weiler, Markus and Weiss, Claudia and
Wilichowski, Ekkehard and Wurster, Claudia and Wunderlich,
Gilbert and Zeller, Daniel and Ziegler, Andreas and
Kirschner, Janbernd and Pechmann, Astrid},
collaboration = {group, SMArtCARE study},
title = {5q{SMA}: standardised retrospective natural history
assessment in 268 patients with four copies of {SMN}2.},
journal = {Journal of neurology},
volume = {271},
number = {5},
issn = {0367-004X},
address = {Heidelberg},
publisher = {Springer},
reportid = {DZNE-2024-00510},
pages = {2787 - 2797},
year = {2024},
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.},
keywords = {Humans / Retrospective Studies / Male / Female / Survival
of Motor Neuron 2 Protein: genetics / Child, Preschool /
Child / Muscular Atrophy, Spinal: genetics / Muscular
Atrophy, Spinal: diagnosis / Infant / Adolescent / Disease
Progression / Age of Onset / Registries / Germany /
Switzerland / Austria: epidemiology / Young Adult / Neonatal
Screening / Infant, Newborn / Adult / SMN2 (Other) / Age of
onset (Other) / Molecular therapies (Other) / Neonatal
screening (Other) / Pre-symptomatic treatment (Other) / SMA
(Other) / Spinal muscular atrophy (Other) / Survival of
Motor Neuron 2 Protein (NLM Chemicals) / SMN2 protein, human
(NLM Chemicals)},
cin = {LIS},
ddc = {610},
cid = {I:(DE-2719)1040260},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC11055798},
pubmed = {pmid:38409538},
doi = {10.1007/s00415-024-12188-5},
url = {https://pub.dzne.de/record/269341},
}