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, Munich, Germany.
Department of Pediatric Neurology, Developmental Neurology and Social Pediatrics, University of Essen, Essen, Germany.
J Neuromuscul Dis. 2022;9(5):597-605. doi: 10.3233/JND-221510.
Early treatment after genetic newborn screening (NBS) for SMA significantly improves outcomes in infantile SMA. However, there is no consensus in the SMA treatment community about early treatment initiation in patients with four copies of SMN2.
Approach to a responsible treatment strategy for SMA patients with four SMN2 copies detected in newborn screening.
Inclusion criteria were a history of SMA diagnosed by NBS, age > 12 months at last examination, and diagnosis of four SMN2 copies at confirmatory diagnosis.
21 patients with SMA and four SMN2 copies were identified in German screening projects over a three-year period. In three of them, the SMN2 copy number had to be corrected later, and three patients were lost to follow-up. Eight of the fifteen patients who were subject to long-term follow-up underwent presymptomatic therapy between 3 and 36 months of age and had no definite disease symptoms to date. Five of the other seven patients who underwent a strict follow-up strategy, showed clinical or electrophysiological disease onset between 1.5 and 4 years of age. In two of them, complete recovery was not achieved despite immediate initiation of treatment after the onset of the first symptoms.
A remarkable proportion of patients with four copies of SMN2 develop irreversible symptoms within the first four years of life, if a wait-and-see strategy is followed. These data argue for a proactive approach, i.e., early initiation of treatment in this subgroup of SMA patients.
在 SMA 的新生儿基因筛查（NBS）后进行早期治疗可显著改善婴儿型 SMA 的预后。然而，在 SMA 治疗领域，对于在 NBS 中检测到四个 SMN2 拷贝的患者，何时开始早期治疗尚未达成共识。
为在新生儿筛查中发现有四个 SMN2 拷贝的 SMA 患者制定负责任的治疗策略。
纳入标准为通过 NBS 诊断的 SMA 病史，末次检查时年龄＞12 个月，和在确证诊断时检测到四个 SMN2 拷贝。
在三年内的德国筛查项目中，共发现 21 例 SMA 患者且具有四个 SMN2 拷贝。其中有三个患者的 SMN2 拷贝数后来需要校正，三个患者失访。在接受长期随访的 15 例患者中，有 8 例在 3 至 36 个月之间接受了症状前治疗，目前尚无明确的疾病症状。在遵循严格随访策略的 7 例患者中，有 5 例在 1.5 至 4 岁之间出现了临床或电生理疾病发作。其中有 2 例尽管在出现首个症状后立即开始治疗，但并未完全恢复。
如果采用等待观察策略，相当一部分具有四个 SMN2 拷贝的患者会在生命的前四年内出现不可逆转的症状。这些数据支持采取积极主动的方法，即对该亚组 SMA 患者尽早开始治疗。
