Vill Katharina, Tacke Moritz, König Anna, Baumann Matthias, Baumgartner Manuela, Steinbach Meike, Bernert Guenther, 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 C, Koelbel Heike, Koehler Cornelia, Kolzter Kirsten, Lochmüller Hanns, Ludolph Albert, 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, Tuerk Matthias, Theophil Manuela, Rauscher Christian, Vorgerd Mathias, Walter Maggie C, Weiler Markus, Weiss Claudia, Wilichowski Ekkehard, Wurster Claudia D, Wunderlich Gilbert, Zeller Daniel, Ziegler Andreas, Kirschner Janbernd, Pechmann Astrid
Department of Pediatric Neurology and Developmental Medicine and LMU Center for Children With Medical Complexity, Dr. Von Hauner Children's Hospital, LMU Hospital, Ludwig-Maximilians-University, 80337, Munich, Germany.
School of Medicine, Klinikum Rechts Der Isar, Department of Human Genetics, Technical University of Munich, Munich, Germany.
J Neurol. 2024 May;271(5):2787-2797. doi: 10.1007/s00415-024-12188-5. Epub 2024 Feb 27.
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.
对5q脊髓性肌萎缩症进行新生儿筛查为早期（理想情况下是症状前）治疗干预提供了可能性。然而，关于拥有4份SMN2基因拷贝的个体的预后数据有限，并且在脊髓性肌萎缩症治疗领域内，对于该亚组患者的早期治疗启动尚未达成共识。为了提供基于证据的疾病进展见解，我们对来自德国、奥地利和瑞士的SMArtCARE注册中心的268例拥有4份SMN2基因拷贝的患者进行了回顾性分析。纳入标准要求有全面的基线数据且诊断不在新生儿筛查范围内。仅纳入疾病修饰治疗开始前的数据。疾病发作的中位年龄为3.0岁，平均年龄为6.4岁。值得注意的是，55%的患者在36个月龄之前出现症状。3%的患者从未学会独立坐立，另有13%的患者从未获得独立行走的能力，33%的能行走患者在疾病过程中丧失了这种能力。43%的患者出现脊柱侧弯，6.3%的患者需要无创通气，1.1%的患者需要管饲。总之，我们的研究与先前的观察结果一致，突出了脊髓性肌萎缩症中显著的表型异质性。重要的是，这项研究提供了新的见解：拥有4份SMN2基因拷贝的患者疾病发作的中位年龄通常发生在学龄期之前，半数患者甚至在3岁之前。这些发现支持对这一亚组症状前诊断的脊髓性肌萎缩症患者采取积极主动的方法，尤其是早期开始治疗。然而，必须认识到该注册中心不会纳入无症状个体。
