117例儿童脊髓性肌萎缩症自然病史分析

doi:10.7499/j.issn.1008-8830.2106025

Abstract
Figure/Table
References(30)
Related Citation (15)
Read Tracking
Download Tracking

Download: PDF (574 KB) HTML
Export: BibTeX | EndNote (RIS) Supporting Info

Abstract Objective To study the natural history of spinal muscular atrophy (SMA) in Chongqing and surrounding areas, China, and to provide a clinical basis for comprehensive management and gene modification therapy for SMA. Methods A retrospective analysis was performed on the medical data and survival status of 117 children with SMA. Results Of the 117 children, 62 (53.0%) had type 1 SMA, 45 (38.5%) had type 2 SMA, and 10 (8.5%) had type 3 SMA, with a median age of onset of 2 months, 10 months, and 15 months, respectively. Compared with the children with type 2 SMA or type 3 SMA, the children with type 1 SMA had significantly shorter time to onset, consultation, and confirmed diagnosis (P<0.05) and a significantly shorter diagnostic time window (age from disease onset to consultation) (P<0.05). Pneumonia as the initial symptom, weakness in head control, crying weakness, and eating difficulty were more commonly observed in children with type 1 SMA (P<0.05). Scoliosis and lower limb joint contracture were more common in children with type 2 SMA than in those with type 1 SMA (P<0.05). All 117 SMA children (100%) had homozygous deletion of the SMN1 gene, and the homozygous deletion of exon 7 was the most common type (68.4%, 80/117). The 6-year survival rate of children with type 1 SMA was only 10%±5%, which was significantly lower than that of children with type 2 or 3 SMA (P<0.05). Age of onset ≤3 months, pneumonia as the initial symptom and weakness in head control were the risk factors for death in children with type 1 SMA (P<0.05). The children with type 2 SMA had non-linear regression of motor ability. Conclusions There are differences in clinical manifestations and survival rates among children with different types of SMA. The children with type 1 SMA have a low survival rate, and those with type 2 SMA may have non-linear regression of motor ability. Early identification and management of SMA should be performed in clinical practice.

	Service

	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors
	YANG Yun-Ying
	YUAN Ping
	LI Mei
	JIANG Li
	HONG Si-Qi

Key words： Spinal muscular atrophy Natural history SMN1 gene Survival analysis Child

Received: 07 June 2021

Cite this article:

YANG Yun-Ying,YUAN Ping,LI Mei et al. Natural history of spinal muscular atrophy in children: an analysis of 117 cases[J]. CJCP, 2021, 23(10): 1038-1043.

URL:

http://www.zgddek.com/EN/10.7499/j.issn.1008-8830.2106025 OR http://www.zgddek.com/EN/Y2021/V23/I10/1038

	Pechmann A, Kirschner J. Diagnosis and new treatment avenues in spinal muscular atrophy[J]. Neuropediatrics, 2017, 48(4): 273-281. PMID: 28571100. DOI: 10.1055/s-0037-1603517.
	Schorling DC, Pechmann A, Kirschner J. Advances in treatment of spinal muscular atrophy—new phenotypes, new challenges, new implications for care[J]. J Neuromuscul Dis, 2020, 7(1): 1-13. PMID: 31707373. PMCID: PMC7029319. DOI: 10.3233/JND-190424.
	3 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. DOI: 10.3760/cma.j.issn.0376-2491.2019.19.006.
	Cao YY, Cheng MM, Qu YJ, et al. Factors associated with delayed diagnosis of spinal muscular atrophy in China and changes in diagnostic delay[J]. Neuromuscul Disord, 2021, 31(6): 519-527. PMID: 33838997. DOI: 10.1016/j.nmd.2021.03.002.
	5 李海冰, 夏雨, 叶文松, 等. 脊髓性肌萎缩症髋关节和脊柱畸形的初步研究[J]. 中华小儿外科杂志, 2020, 41(10): 926-932. DOI: 10.3760/cma.j.cn421158-20200217-00081.
	Lipnick SL, Agniel DM, Aggarwal R, et al. Systemic nature of spinal muscular atrophy revealed by studying insurance claims[J]. PLoS One, 2019, 14(3): e0213680. PMID: 30870495. PMCID: PMC: 6417721. DOI: 10.1371/journal.pone.0213680.
	Wijngaarde CA, Huisman A, Wadman RI, et al. Abnormal coagulation parameters are a common non-neuromuscular feature in patients with spinal muscular atrophy[J]. J Neurol Neurosurg Psychiatry, 2020, 91(2): 212-214. PMID: 31515301. DOI: 10.1136/jnnp-2019-321506.
	Finkel RS, Sejersen T, Mercuri E, et al. 218th ENMC International Workshop: revisiting the consensus on standards of care in SMA Naarden, the Netherlands, 19-21 February 2016[J]. Neuromuscul Disord, 2017, 27(6): 596-605. PMID: 28392274. DOI: 10.1016/j.nmd.2017.02.014.
	王旻晋, 王军, 白梦鸽, 等. 中国西南地区汉族脊肌萎缩症患者SMA相关基因分子特征[J]. 四川大学学报(医学版), 2016, 47(6): 936-940. PMID: 28598128. DOI: 10.13464/j.scuxbyxb.2016.06.025.
	宋昉, 瞿宇晋, 邹丽萍, 等. 疑似脊髓性肌萎缩症患儿338例的运动神经元存活基因分析[J]. 中华儿科杂志, 2008, 46(12): 919-923. PMID: 19134255. DOI: 10.3321/j.issn:0578-1310.2008.12.009.
	李鸿, 王怀礼, 单崇敏. 小儿进行性脊髓性肌萎缩83例临床分析[J]. 中华儿科杂志, 2004, 42(10): 762-764. PMID: 16221347. DOI: 10.3760/j.issn:0578-1310.2004.10.013.
	Finkel RS, McDermott MP, Kaufmann P, et al. Observational study of spinal muscular atrophy type I and implications for clinical trials[J]. Neurology, 2014, 83(9): 810-817. PMID: 25080519. PMCID: PMC4155049. DOI: 10.1212/WNL.0000000000000741.
	Alvarez K, Suarez B, Palomino MA, et al. Observations from a nationwide vigilance program in medical care for spinal muscular atrophy patients in Chile[J]. Arq Neuropsiquiatr, 2019, 77(7): 470-477. PMID: 31365638. DOI: 10.1590/0004-282X20190073.
	Zhang YH, He J, Zhang YQ, et al. The analysis of the association between the copy numbers of survival motor neuron gene 2 and neuronal apoptosis inhibitory protein genes and the clinical phenotypes in 40 patients with spinal muscular atrophy: observational study[J]. Medicine (Baltimore), 2020, 99(3): e18809. PMID: 32011487. PMCID: PMC7220227. DOI: 10.1097/MD.0000000000018809.
	Oskoui M, Levy G, Garland CJ, et al. The changing natural history of spinal muscular atrophy type 1[J]. Neurology, 2007, 69(20): 1931-1936. PMID: 17998484. DOI: 10.1212/01.wnl.0000290830.40544.b9.
	Zerres K, Rudnik-Sch?neborn S. Natural history in proximal spinal muscular atrophy. Clinical analysis of 445 patients and suggestions for a modification of existing classifications[J]. Arch Neurol, 1995, 52(5): 518-523. PMID: 7733848. DOI: 10.1001/archneur.1995.00540290108025.
	Ge XS, Bai JL, Lu YY, et al. The natural history of infant spinal muscular atrophy in China: a study of 237 patients[J]. J Child Neurol, 2012, 27(4): 471-477. PMID: 21954429. DOI: 10.1177/0883073811420152.
	Chung BHY, Wong VCN, Ip P. Spinal muscular atrophy: survival pattern and functional status[J]. Pediatrics, 2004, 114(5): e548-e553. PMID: 15492357. DOI: 10.1542/peds.2004-0668.
	Kolb SJ, Coffey CS, Yankey JW, et al. Natural history of infantile-onset spinal muscular atrophy[J]. Ann Neurol, 2017, 82(6): 883-891. PMID: 29149772. PMCID: PMC5776712. DOI: 10.1002/ana.25101.
	张琴, 缪红军. 儿童脊髓性肌萎缩症的呼吸道管理[J]. 中华儿科杂志, 2019, 57(10): 810-812. PMID: 31594072. DOI: 10.3760/cma.j.issn.0578-1310.2019.10.018.
	Mercuri E, Lucibello S, Pera MC, et al. Long-term progression in type II spinal muscular atrophy: a retrospective observational study[J]. Neurology, 2019, 93(13): e1241-e1247. PMID: 31451515. PMCID: PMC7011866. DOI: 10.1212/WNL.0000000000008166.
	Chabanon A, Seferian AM, Daron A, et al. Prospective and longitudinal natural history study of patients with type 2 and 3 spinal muscular atrophy: baseline data NatHis-SMA study[J]. PLoS One, 2018, 13(7): e0201004. PMID: 30048507. PMCID: PMC6062049. DOI: 10.1371/journal.pone.0201004.
	Mercuri E, Bertini E, Iannaccone ST. Childhood spinal muscular atrophy: controversies and challenges[J]. Lancet Neurol, 2012, 11(5): 443-452. PMID: 22516079. DOI: 10.1016/S1474-4422(12)70061-3.
	Finkel RS, Mercuri E, Meyer OH, et al. Diagnosis and management of spinal muscular atrophy: part 2: pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics[J]. Neuromuscul Disord, 2018, 28(3): 197-207. PMID: 29305137. DOI: 10.1016/j.nmd.2017.11.004.
	Mercuri E, Finkel RS, Muntoni F, et al. Diagnosis and management of spinal muscular atrophy: part 1: recommendations for diagnosis, rehabilitation, orthopedic and nutritional care[J]. Neuromuscul Disord, 2018, 28(2): 103-115. PMID: 29290580. DOI: 10.1016/j.nmd.2017.11.005.
	冯艺杰, 毛姗姗. 脊髓性肌萎缩症的药物治疗研究进展[J]. 中华儿科杂志, 2020, 58(10): 858-861. PMID: 32987471. DOI: 10.3760/cma.j.cn112140-20200320-00280.
	Finkel RS, Mercuri E, Darras BT, et al. Nusinersen versus sham control in infantile-onset spinal muscular atrophy[J]. N Engl J Med, 2017, 377(18): 1723-1732. PMID: 29091570. DOI: 10.1056/NEJMoa1702752.
	Mercuri E, Darras BT, Chiriboga CA, et al. Nusinersen versus sham control in later-onset spinal muscular atrophy[J]. N Engl J Med, 2018, 378(7): 625-635. PMID: 29443664. DOI: 10.1056/NEJMoa1710504.
	Baranello G, Darras BT, Day JW, et al. Risdiplam in type 1 spinal muscular atrophy[J]. N Engl J Med, 2021, 384(10): 915-923. PMID: 33626251. DOI: 10.1056/NEJMoa2009965.
	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. PMID: 33743238. DOI: 10.1016/S1474-4422(21)00001-6.