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