Fatal Thrombotic Microangiopathy Case following Adeno-Associated Viral SMN Gene Therapy

Adeno-Associated Virus (AAV) gene therapies are highly promising, such as the onasemnogene abeparvovec (Zolgensma®) in Spinal Muscle Atrophy (SMA). We report the first case of fatal systemic Thrombotic MicroAngiopathy (TMA) following onasemnogene abeparvovec in a 6-month-old child with SMA type 1, carrying a potential genetic predisposition in the Complement Factor I gene. Other cases of TMA have recently been reported after onasemnogene abeparvovec, and after AAV9 minidystrophin therapy in the Duchenne muscular dystrophy. The risk-benefit ratio of this therapy must therefore be assessed. Early recognition of TMA and targeted immunotherapy are fundamental to ensure the safety of patients treated with AAV gene therapies.