2021 Volume 53 Issue 2 Pages 142-145
Nusinersen, an antisense oligonucleotide that targets survival motor neuron (SMN) 2, was approved as a new therapeutic approach for spinal muscular atrophy (SMA). Although early intervention is recommended in patients with infantile-onset SMA, there are limited data about the efficacy of nusinersen for the very severe fetal-onset form of SMA (type 0). We report the case of a 2-year and 3-month-old boy with SMA type 0, who was treated with nusinersen. The patient presented with severe muscle weakness, marked hypotonia, respiratory distress, and joint contracture at birth. At 9 weeks of age, a genetic analysis revealed homozygous deletion of the SMN1 gene and two copies of the SMN2 gene. Based on these findings and presumed intrauterine-onset-related symptoms, a diagnosis of SMA type 0 was made. The intrathecal injection of nusinersen was started at 10 weeks of age. One week later, the patient exhibited improvements in spontaneous movement, starting in his left forearm. However, at 4 months of age he underwent tracheotomy due to worsening pharyngomalacia and required mechanical ventilation. After surgery, his respiratory condition stabilized and his motor function improved steadily. At discharge (at 9 months of age), he required sustained ventilator support, tube-feeding and frequent tracheal suctioning. After discharge, he continued receiving nusinersen treatment. No obvious adverse events were noted. At his last visit, he was unable to speak, but was able to sit independently for a minute. Although the ventilator could be removed for one hour, he remained ventilator-dependent. The patient's CHOP-INTEND score increased from 3 points at treatment initiation to 47 points. This case suggests that early diagnosis and treatment with nusinersen may improve the motor function of SMA patients, even those with SMA type 0. However, the long-term effects of nusinersen on motor function and other multi-organ symptoms in SMA type 0 should be examined further.
