儿童脊髓性肌萎缩症症状前治疗专家共识（2025版）

doi:10.12372/jcp.2025.25e0953

摘要/Abstract

摘要：

脊髓性肌萎缩症（SMA）是一种婴幼儿常见致死致残性神经肌肉疾病，因脊髓前角运动神经元退化变性导致肢体出现进行性肌无力与肌萎缩。近年来疾病修正治疗药物的出现和应用正逐渐改变SMA的自然病史，但药物疗效与起始治疗年龄及治疗前病程等因素密切相关，而症状前治疗更有望使患儿存活且获得近于正常人的运动里程碑。本共识组织全国相关领域专家，围绕以下主题达成共识：症状前SMA诊断、治疗决策制定、随访管理及家长沟通要点等，以期为儿童SMA症状前治疗的临床实践提供规范和指导。

关键词: 脊髓性肌萎缩症, 运动神经元存活基因1, 运动神经元存活基因2, 症状前治疗, 新生儿筛查

Abstract:

Spinal muscular atrophy (SMA) is a common fatal and disabling neuromuscular disease in infants and young children, caused by the degeneration of spinal anterior horn motor neurons, leading to progressive muscle weakness and atrophy in the limbs. In recent years, the emergence and application of disease-modifying therapies are gradually changing the natural history of SMA. However, the efficacy of these therapies is closely related to factors such as the age at treatment initiation and the pre-treatment disease course. Pre-symptomatic treatment is more promising to enable the affected children to survive and achieve near-normal motor milestones. This consensus was developed by experts from relevant fields, focusing on the following themes: pre-symptomatic SMA diagnosis, treatment decision-making, follow-up management, and key points for parental communication, with the aim of providing standards and guidance for clinical practices of pre-symptomatic treatment of pediatric SMA.

Key words: spinal muscular atrophy, survival motor neuron 1, survival motor neuron 2, pre-symptomatic treatment, newborn screening

中图分类号:

. 儿童脊髓性肌萎缩症症状前治疗专家共识（2025版）[J]. 临床儿科杂志, 2025, 43(9): 643-651.

参考文献 58

[1]	Mercuri E, Sumner CJ, Muntoni F, et al. Spinal muscular atrophy[J]. Nat Rev Dis Primers, 2022, 8(1): 1-16.
[2]	Verhaart IEC, Robertson A, Wilson IJ, et al. Prevalence, incidence and carrier frequency of 5q-linked spinal muscular atrophy - a literature review[J]. Orphanet J Rare Dis, 2017, 12(1): 124. doi: 10.1186/s13023-017-0671-8 pmid: 28676062
[3]	Wirth B, Karakaya M, Kye MJ, et al. Twenty-five years of spinal muscular atrophy research: from phenotype to genotype to therapy, and what comes next[J]. Annu Rev Genomics Hum Genet, 2020, 21:231-261. doi: 10.1146/annurev-genom-102319-103602 pmid: 32004094
[4]	Nishio H, Niba ETE, Saito T, et al. Spinal muscular atrophy: the past, present, and future of diagnosis and treatment[J]. Int J Mol Sci, 2023, 24(15): 11939.
[5]	Giess D, Erdos J, Wild C. An updated systematic review on spinal muscular atrophy patients treated with nusinersen, onasemnogene abeparvovec (at least 24 months), risdiplam (at least 12 months) or combination therapies[J]. Eur J Paediatr Neurol, 2024, 51: 84-92.
[6]	Govoni A, Gagliardi D, Comi GP, et al. Time is motor neuron: therapeutic window and its correlation with pathogenetic mechanisms in spinal muscular atrophy[J]. Mol Neurobiol, 2018, 55(8): 6307-6318. doi: 10.1007/s12035-017-0831-9 pmid: 29294245
[7]	Crawford TO, Swoboda KJ, De Vivo DC, et al. Continued benefit of nusinersen initiated in the presymptomatic stage of spinal muscular atrophy: 5-year update of the NURTURE study[J]. Muscle Nerve, 2023, 68(2): 157-170. doi: 10.1002/mus.27853 pmid: 37409780
[8]	Shell RD, McGrattan KE, Hurst-Davis R, et al. Onasemnogene abeparvovec preserves bulbar function in infants with presymptomatic spinal muscular atrophy: a post-hoc analysis of the SPR1NT trial[J]. Neuromuscul Disord, 2023, 33(8): 670-676.
[9]	Strauss KA, Farrar MA, Muntoni F, et al. Onasemnogene abeparvovec for presymptomatic infants with two copies of SMN2 at risk for spinal muscular atrophy type 1: the Phase III SPR1NT trial[J]. Nat Med, 2022, 28(7): 1381-1389. doi: 10.1038/s41591-022-01866-4 pmid: 35715566
[10]	Strauss KA, Farrar MA, Muntoni F, et al. Onasemnogene abeparvovec for presymptomatic infants with three copies of SMN2 at risk for spinal muscular atrophy: the Phase III SPR1NT trial[J]. Nat Med, 2022, 28(7): 1390-1397. doi: 10.1038/s41591-022-01867-3 pmid: 35715567
[11]	Cooper K, Nalbant G, Sutton A, et al. Systematic review of presymptomatic treatment for spinal muscular atrophy[J]. Int J Neonatal Screen, 2024, 10(3): 56.
[12]	Kalkman S, Wevers RA, Wijburg FA, et al. A framework for evaluating long-term impact of newborn screening[J]. Eur J Hum Genet, 2024, 32(2): 146-149.
[13]	Hsu CC, Sandford BA. The Delphi technique - making sense of consensus[J]. Pract Assess Res Eval, 2007, 12(10): 1-8.
[14]	Sinha IP, Smyth RL, Williamson PR. Using the Delphi technique to determine which outcomes to measure in clinical trials: recommendations for the future based on a systematic review of existing studies[J]. PLoS Med, 2011, 8(1): e1000393.
[15]	Farrar MA, Kiernan MC, Kariyawasam DS. Presymptomatic spinal muscular atrophy: a cautionary approach to the proposed new terminology[J]. Brain, 2023, 146(9): e65-e66.
[16]	Dangouloff T, Vrščaj E, Servais L, et al. Newborn screening programs for spinal muscular atrophy worldwide: Where we stand and where to go[J]. Neuromuscul Disord, 2021, 31(6): 574-582.
[17]	中华医学会神经病学分会, 中华医学会神经病学分会神经遗传学组. 脊髓性肌萎缩症中国三级预防指南[J]. 中华神经科杂志, 2023, 56(5): 476-484.
	Chinese Society of Neurology, Chinese Society of Neurogenetics. Chinese guidelines for three levels of prevention of spinal muscular atrophy[J]. Zhonghua Shenjingke Zazhi, 2023, 56(5): 476-484.
[18]	中国研究型医院学会神经科学专业委员会, 中国出生缺陷干预救助基金会神经与肌肉疾病防控专项基金组织专家组. 脊髓性肌萎缩症新生儿筛查专家共识(2023版)[J]. 中华医学杂志, 2023, 103(27): 2075-2081.
	Society for Neuroscience and Neurology, Chinese Research Hospital Association, Dedicated Fund for Neuromuscular Disorders, March of Dimes Birth Defects Foundation of China. Expert consensus on newborn screening for spinal muscular atrophy (2023 edition)[J]. Zhonghua Yixue Zazhi, 2023, 103(27): 2075-2081.
[19]	Wijaya YOS, Purevsuren J, Harahap NIF, et al. Assessment of spinal muscular atrophy carrier status by determining SMN1 copy number using dried blood spots[J]. Int J Neonatal Screen, 2020, 6(2): 43.
[20]	Chien YH, Chiang SC, Weng WC, et al. Presymptomatic diagnosis of spinal muscular atrophy through newborn screening[J]. J Pediatr, 2017, 190: 124-129.
[21]	Schroth M, Deans J, Arya K, et al. Spinal muscular atrophy update in best practices: recommendations for diagnosis considerations[J]. Neurol Clin Pract, 2024, 14(4): e200310.
[22]	Blaschek A, Kölbel H, Schwartz O, et al. Newborn screening for SMA-can a wait-and-see strategy be responsibly justified in patients with four SMN2 copies?[J]. J Neuromuscul Dis, 2022, 9(5): 597-605.
[23]	Glascock J, Sampson J, Connolly AM, et al. Revised recommendations for the treatment of infants diagnosed with spinal muscular atrophy via newborn screening who have 4 copies of SMN2[J]. J Neuromuscul Dis, 2020, 7(2): 97-100.
[24]	Ricci M, Cicala G, Capasso A, et al; ITASMAC Working Group. Clinical phenotype of pediatric and adult patients with spinal muscular atrophy with four SMN2 copies: are they really all stable?[J]. Ann Neurol, 2023, 94(6): 1126-1135.
[25]	Trollmann R, Johannsen J, Vill K, et al. Postnatal management of preterm infants with spinal muscular atrophy: experience from German newborn screening[J]. Orphanet J Rare Dis, 2024, 19(1): 353. doi: 10.1186/s13023-024-03362-z pmid: 39327607
[26]	Gagliardi D, Canzio E, Orsini P, et al. Early spinal muscular atrophy treatment following newborn screening: a 20-month review of the first Italian regional experience[J]. Ann Clin Transl Neurol, 2024, 11(5): 1090-1096.
[27]	Lee BH, Deng S, Chiriboga CA, et al. Newborn screening for spinal muscular atrophy in New York State: Clinical outcomes from the first 3 years[J]. Neurology, 2022, 99(14): e1527-e1537.
[28]	Aragon-Gawinska K, Mouraux C, Dangouloff T, et al. Spinal muscular atrophy treatment in patients identified by newborn screening-a systematic review[J]. Genes (Basel), 2023, 14(7): 1377.
[29]	Finkel R, Farrar M, Vlodavets D, et al. FP.24 RAINBOWFISH: Preliminary efficacy and safety data in Risdiplam-treated infants with presymptomatic spinal muscular atrophy (SMA)[J]. Neuromuscul Disord, 2022, 32: S85-S86.
[30]	Niri F, Nicholls J, Baptista Wyatt K, et al. Alberta spinal muscular atrophy newborn screening-results from year 1 pilot project[J]. Int J Neonatal Screen, 2023, 9(3): 42.
[31]	Day JW, Finkel RS, Chiriboga CA, et al. Onasemnogene abeparvovec gene therapy for symptomatic infantile-onset spinal muscular atrophy in patients with two copies of SMN2 (STR1VE): an open-label, single-arm, multicentre, phase 3 trial[J]. Lancet Neurol, 2021, 20(4): 284-293.
[32]	Mendell JR, Al-Zaidy S, Shell R, et al. Single-dose gene-replacement therapy for spinal muscular atrophy[J]. N Engl J Med, 2017, 377(18): 1713-1722.
[33]	Novartis. Efficacy and Safety of Intrathecal OAV101 (AVXS-101) in Pediatric Patients With Type 2 Spinal Muscular Atrophy (SMA) (STEER) [EB/OL]. (2025-03-21) [2025-04-25]. https://clinicaltrials.gov/study/NCT05089656?cond=Spinal%20Muscular%20Atrophy&intr=OAV101&rank=4.
[34]	Kariyawasam DS, D'Silva AM, Sampaio H, et al. Newborn screening for spinal muscular atrophy in Australia: a non-randomised cohort study[J]. Lancet Child Adolesc Health, 2023, 7(3): 159-170. doi: 10.1016/S2352-4642(22)00342-X pmid: 36669516
[35]	Schwartz O, Vill K, Pfaffenlehner M, et al; SMARTCARE study group. Clinical effectiveness of newborn screening for spinal muscular atrophy: a nonrandomized controlled trial[J]. JAMA Pediatr, 2024, 178(6): 540-547. doi: 10.1001/jamapediatrics.2024.0492 pmid: 38587854
[36]	冯艺杰, 余燚成, 颜悦, 等. 诺西那生钠治疗症状前脊髓性肌萎缩症患儿4例[J]. 中华儿科杂志, 2024, 62(8): 786-788.
	Feng YJ, Yu YC, Yan Y, et al. Nusinersen in the treatment of 4 children with presymptomatic spinal muscular atrophy[J]. Zhonghua Erke Zazhi, 2024, 62(8): 786-788.
[37]	Tizzano EF, Quijano-Roy S, Servais L, et al RESTORE Study Group.; Outcomes for patients in the RESTORE registry with spinal muscular atrophy and four or more SMN2 gene copies treated with onasemnogene abeparvovec[J]. Eur J Paediatr Neurol, 2024, 53: 18-24.
[38]	Cuscó I, Bernal S, Blasco-Pérez L, et al. Practical guidelines to manage discordant situations of SMN2 copy number in patients with spinal muscular atrophy[J]. Neurol Genet, 2020, 6(6): e530.
[39]	Romanelli Tavares VL, Mendonça RH, Toledo MS, et al. Integrated approaches and practical recommendations in patient care identified with 5q spinal muscular atrophy through newborn screening[J]. Genes (Basel), 2024, 15(7): 858.
[40]	北京医学会罕见病分会, 北京医学会医学遗传学分会, 北京医学会神经病学分会神经肌肉病学组, 等. 脊髓性肌萎缩症多学科管理专家共识[J]. 中华医学杂志, 2019, 99(19): 1460-1467.
[41]	Varone A, Esposito G, Bitetti I. Spinal muscular atrophy in the era of newborn screening: how the classification could change[J]. Front Neurol, 2025, 16: 1542396.
[42]	De Vivo DC, Bertini E, Swoboda KJ, et al; NURTURE Study Group. Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: interim efficacy and safety results from the Phase 2 NURTURE study[J]. Neuromuscul Disord, 2019, 29(11): 842-856.
[43]	WHO Multicentre Growth Reference Study Group. WHO Motor Development Study: windows of achievement for six gross motor development milestones[J]. Acta Paediatr Suppl, 2006, 450: 86-95.
[44]	Kolb SJ, Coffey CS, Yankey JW, et al; NeuroNEXT Clinical Trial Network on behalf of the NN101 SMA Biomarker Investigators. Natural history of infantile-onset spinal muscular atrophy[J]. Ann Neurol, 2017, 82(6): 883-891. doi: 10.1002/ana.25101 pmid: 29149772
[45]	Barrois R, Barnerias C, Deladrière E, et al. A new score combining compound muscle action potential (CMAP) amplitudes and motor score is predictive of motor outcome after AVXS-101 (Onasemnogene Abeparvovec) SMA therapy[J]. Neuromuscul Disord, 2023, 33(4): 309-314.
[46]	Peng Y, Feng L, Wu J, et al. Motor function and compound muscle action potential amplitude in children with spinal muscular atrophy treated with nusinersen[J]. Brain Dev, 2025, 47(1): 104316.
[47]	Ueda Y, Egawa K, Kawamura K, et al. Nusinersen induces detectable changes in compound motor action potential response in spinal muscular atrophy type 1 patients with severe impairment of motor function[J]. Brain Dev, 2024, 46(3): 149-153.
[48]	Weng WC, Hsu YK, Chang FM, et al. CMAP changes upon symptom onset and during treatment in spinal muscular atrophy patients: lessons learned from newborn screening[J]. Genet Med, 2021, 23(2): 415-420. doi: 10.1038/s41436-020-00987-w pmid: 33033402
[49]	Vangoor V R, Gomes-Duarte A, Pasterkamp RJ. Long non-coding RNAs in motor neuron development and disease[J]. J Neurochem, 2021, 156(6): 777-801.
[50]	Boido M, Vercelli A. Neuromuscular junctions as key contributors and therapeutic targets in spinal muscular atrophy[J]. Front Neuroanat, 2016, 10: 6. doi: 10.3389/fnana.2016.00006 pmid: 26869891
[51]	Darras BT, Crawford TO, Finkel RS, et al. Neurofilament as a potential biomarker for spinal muscular atrophy[J]. Ann Clin Transl Neurol, 2019, 6(5): 932-944.
[52]	Badina M, Bejan GC, Sporea C, et al. Changes in pNFH levels in cerebrospinal fluid and motor evolution after the loading dose with Nusinersen in different types of spinal muscular atrophy[J]. Medicina (Kaunas), 2023, 59(7): 1244.
[53]	Brkušanin M, Kosać A, Branković-Srećković V, et al. Phosphorylated neurofilament heavy chain in cerebrospinal fluid and plasma as a Nusinersen treatment response marker in childhood-onset SMA individuals from Serbia[J]. Front Neurol, 2024, 15: 1394001.
[54]	Vermunt L, Otte M, Verberk IMW, et al. Age- and disease-specific reference values for neurofilament light presented in an online interactive support interface[J]. Ann Clin Transl Neurol, 2022, 9(11): 1832-1837.
[55]	Nitz E, Smitka M, Schallner J, et al. Serum neurofilament light chain in pediatric spinal muscular atrophy patients and healthy children[J]. Ann Clin Transl Neurol, 2021, 8(10): 2013-2024.
[56]	Rich KA, Fox A, Yalvac M, et al. Neurofilament levels in CSF and serum in an adult SMA cohort treated with Nusinersen[J]. J Neuromuscul Dis, 2022, 9(1): 111-119.
[57]	Jin J, Wei J, Feng Y, et al. Plasma neurofilament light chain in Chinese children with later-onset spinal muscular atrophy[J]. Clin Chem Lab Med, 2022, 60(10): e237-e239.
[58]	Jin J, Feng Y, Huang S, et al. Value of plasma neurofilament light chain for monitoring efficacy in children with later-onset spinal muscular atrophy under nusinersen treatment[J]. Clin Chem Lab Med, 2024, 62(6): e132-e135.