1044 Spinal Muscular Atrophy and Sleep: Double-Trouble

Abstract

Abstract Introduction Spinal muscular atrophy (SMA) is a rare neuromuscular disorder which leads to progressive muscular weakness and respiratory impairment. Affected patients experience a variety of sleep problems including obstructive sleep apnea, nocturnal hypoventilation, and increased sleep disturbances. As of 2019, the first gene therapy was approved to treat patients with SMA under the age of 2, onasemnogene abeparvovec-xioi (ZolgensmaTM), with expedited approval due to findings of improved motor function and milestone achievement as well as survivability. We describe an unusual case of twins with SMA whom developed worsening obstructive sleep apnea after gene therapy. Report of case(s) The patients are a set of 3-year-old male twins with past medical history significant for premature lung disease related to extreme prematurity at 24-weeks and SMA type 2. They were initially referred for polysomnography (PSG) at 1 year of age for evaluation of snoring and as a precaution related to their underlying diagnosis. Physical examination findings were significant for tongue atrophy with fasciculations and generalized muscular weakness which spared the face. Neither twin achieved gross motor milestones of standing or walking to that point. Both patients would receive the gene therapy infusion at 1 year, 8 months with subsequent improvement in hypotonia and ability to ambulate independently. For twin A, baseline PSG at age 1 showed mild obstructive sleep apnea (apnea-hypopnea index (AHI)= 3.24 events per hour) without any signs of hypoxemia or hypoventilation. By comparison, the patient’s post-gene therapy PSG (around 1.5 years post-infusion) at age 3, showed progression to moderate obstruction (obstructive AHI of 6.03 events per hour). For twin B, baseline PSG showed moderate obstructive sleep apnea (AHI=9.09 events per hour) which progressed into the severe range (AHI= 11.90 events per hour) over the same time course. Conclusion Sleep-disordered breathing in SMA is a commonly diagnosed entity. While airway obstruction related to hypotonia would be an expected contributor, our case suggests that despite recovery of motor function through use of gene therapy, clinicians should maintain a high level of suspicion for sleep problems with strong consideration for PSG due to the risk of sub-clinical progression of sleep obstruction. Support (if any)