A rare but formidable complication of gene therapy in SMA

Gene therapy for spinal muscular atrophy (SMA) has involved some 40 French infants to date. The onesamnogene abeparvovec (Zolgensma®) was administered in a single intravenous injection. Clinicians in Paris and Nantes report the occurrence in one of them of thrombotic microangiopathy (TMA), a serious and potentially lethal complication directly related to the treatment:

  • this child, treated at the age of six months, presented a picture comparable to a haemolytic uraemic syndrome a few days after the gene therapy,
  • she did not respond to further treatment of TAM with eculizimab, resulting in a fatal outcome,
  • agenetic susceptibility to complement factor abnormalities could be a risk factor in this case.

Early detection and appropriate treatment of MAT is essential.


Fatal Thrombotic Microangiopathy Case following Adeno-Associated Viral SMN Gene Therapy. Guillou J, De Pellegars A, Porcheret F et al. Blood Adv. 2022 May 18:bloodadvances.2021006419.