Background: Spinal Muscular Atrophy (SMA) is a rare, neuromuscular disorder that results in the degeneration of lower motor neurons, leading to severe muscular atrophy and weakness. Early treatment with SMN1 gene transfer (onasemnogene abeparvovec) has demonstrated to be effective as a treatment option. Liver injury is a known potential side effect. Cytomegalovirus (CMV) is a highly prevalent virus in adult populations that typically does not produce symptoms for healthy individuals. However, CMV does pose a risk for patients with weakened immune systems.
Methods: Describe the course of a 10-month-old baby girl diagnosed with SMA type 1 after receiving onasemnogene abeparvovec-xioi and developing transaminitis unresponsive to escalating steroid treatment.
Results: The patient was initially admitted post-gene transfer day #3 for inability for parents to administer oral steroids. Routine labs Elevations in liver enzymes 5 days following infusion onasemnogene abeparvovec-xioi were elevated to >3x baseline levels. She was started on a course of 20 mg/kg/d of IV methylprednisolone. After 3 days of this course, her LFTs continued to increase. Her IV methylprednisolone course was extended to 5 days. LFTs continued to increase with ALT peaking at 864 U/L (upper limit of normal is <52 U/L) and GGT at 91 U/L (upper limit of normal is <55). After further investigation, she was found to be CMV positive and confirmed with PCR 14 days after gene transfer. She then underwent a course of valganciclovir resulting in resolution of her transaminitis. Conclusion: Elevations in liver function tests are not uncommon in children with Spinal Muscular Atrophy treated with onasemnogene abeparvovec. In cases where there is no response to escalation of steroid treatment, other causes need to be investigated. Infection with CMV should be considered as a potential cause of LFT elevations in such cases.