SMN1基因复合杂合变异脊髓性肌萎缩症患者疾病修正治疗的临床疗效分析

doi:10.12372/jcp.2025.24e1371

摘要/Abstract

摘要：

目的探讨SMN1基因复合杂合变异所致脊髓性肌萎缩症（SMA）接受疾病修正治疗的临床疗效。方法回顾性收集2例复合杂合变异SMA患儿的临床资料、治疗经过以及随访结果，并结合国内外相关的病例报道进行分析。结果 2例患儿均为SMAⅠ型，SMN1基因存在外显子7杂合缺失和1处微小变异（分别为c.188C>A和c.683T>A）。其中例1为4岁4个月男性患儿，7月龄起病时开始康复训练，1岁6个月接受诺西那生钠治疗，3岁加用利司扑兰联合治疗，3岁10个月停康复。治疗后患儿运动功能缓慢进步，获得翻身至侧位和扶坐能力，目前可扶坐。例2为1岁8个月女性患儿，4月龄起病时开始康复训练，7月龄口服利司扑兰，因皮肤颜色持续变黑，于1岁5个月改为诺西那生钠治疗。药物治疗结合康复训练后患儿运动功能显著进步，获得独坐和扶站运动里程碑，目前可独站7~8秒、跨步。结论疾病修正治疗能改善复合杂合变异SMA患儿的总体预后，并提高患儿的运动功能。

关键词: 脊髓性肌萎缩症, 复合杂合变异, 疾病修正治疗, 临床疗效, 儿童

Abstract:

Objective To investigate the clinical efficacy of disease-modifying therapies (DMTs) in spinal muscular atrophy (SMA) patients with SMN1 gene compound heterozygous variants. Methods A retrospective analysis was performed on two cases with SMN1 compound heterozygous SMA, including clinical data, treatment approaches, and prognosis. Clinical findings were contextualized through a systematic literature review of analogous cases. Results Two SMA type I patients exhibited SMN1 compound heterozygous: a 4-year-old male (Patient 1) with exon 7 heterozygous deletion and c.188C>A variation, and a 1.7-year-old female (Patient 2) with exon 7 heterozygous deletion and c.683T>A variation. Patient 1 initiated rehabilitation at 7 months of age, received nusinersen treatment at 1 year and 6 months, added risdiplam as combination therapy at 3 years, and discontinued rehabilitation at 3 years and 10 months. Following DMTs, the patient showed slow progress in motor function, acquiring the ability to roll over to the side and sit with support, and is currently able to sit with assistance. Patient 2 started rehabilitation at 4 months of age, received risdiplam at 7 months, and switched to nusinersen treatment at 1 year and 5 months due to persistent darkening of skin color. The combination of DMTs and rehabilitation resulted in significant improvement in the patient's motor function, achieving milestones such as sitting independently and standing with support. Currently, she can stand independently for 7-8 seconds and take steps. Conclusion DMTs can improve the overall prognosis of children with compound heterozygous SMA and enhance their motor function.

Key words: spinal muscular atrophy, compound heterozygous mutation, disease-modifying therapy, clinical efficacy, child

中图分类号:

段浩林, 张慈柳, 熊娟, 庞楠, 尹飞, 彭镜. SMN1基因复合杂合变异脊髓性肌萎缩症患者疾病修正治疗的临床疗效分析[J]. 临床儿科杂志, 2025, 43(7): 543-548.

DUAN Haolin, ZHANG Ciliu, XIONG Juan, PANG Nan, YIN Fei, PENG Jing. Clinical efficacy analysis of disease-modifying therapies for spinal muscular atrophy with SMN1 gene compound heterozygous variants[J]. Journal of Clinical Pediatrics, 2025, 43(7): 543-548.

图/表 4

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