144P Gene therapy for Spinal Muscular Atrophy amid the dengue outbreak in Brazil: a case report

Dengue fever is a mosquito-borne viral disease prevalent in tropical and subtropical regions globally, primarily spread by the Aedes aegypti mosquito. It manifests in a spectrum from mild flu-like symptoms to severe, life-threatening presentations. Among the classic laboratory manifestations, we observe thrombocytopenia and alterations in liver enzymes, which are mostly asymptomatic but can potentially evolve into more severe conditions. Given that these same laboratory changes can also be observed following therapy with onasemnogene abeparvovec (OA), the occurrence of dengue in patients after infusion may lead to potential complications. To describe the case of a patient with SMA treated with OA who developed dengue during the corticosteroid withdrawal phase. This is a patient with Type I spinal muscular atrophy (SMA), diagnosed at 6 months of age (with 2 copies of the SMN2 gene) due to severe respiratory complications from an infectious episode. After diagnosis, the patient began treatment with Risdiplam, presenting good response thereafter until the age of 9 months when gene therapy was infused. The patient was taking prednisolone at a dose of 1 mg/kg for one month. Only mild thrombocytopenia (120,000/mm³) and an elevation in transaminases less than 2 times the upper limit of normal were observed. One month after treatment initiation, as per protocol, a gradual reduction of corticosteroid therapy was started, and by the eighth week post-infusion, the patient was on a 0.25 mg/kg dose of prednisolone. At this point, the patient began to exhibit symptoms of fever, lethargy, red spots on skin, a thrombocytopenia of 80,000/mm³ and transaminase levels elevated to three times the upper limit of normality. Considering the concurrent dengue outbreak in Brazil at the time, serology was ordered and returned positive. Since there were no similar cases described in the literature, we decided to withhold prednisolone tapering, and to recollect samples every 2 to 3 days. Eight days after the onset of symptoms, there was an improvement in laboratory findings with normalization of all tests. At this point, we then decided to discontinue the corticosteroid therapy. This is the first documented case in the medical literature of dengue following gene therapy infusion for SMA. Despite the patient's favorable outcome without specific interventions, this case highlights the potential for an arboviral infection to cause laboratory changes that could exacerbate those commonly observed in patients treated with OA. It is also important to highlight that Infections in earlier phases post-infusion, where thrombocytopenia and hepatic changes may be more pronounced, could lead to potentially serious complications. In this context, dengue protection measures and/or immunization should be reinforced in this population of patients from endemic areas, along with the standard care following gene therapy.