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Case Reports
. 2022 Jul 26;6(14):4266-4270.
doi: 10.1182/bloodadvances.2021006419.

Fatal thrombotic microangiopathy case following adeno-associated viral SMN gene therapy

Julia Guillou  1 , Alice de Pellegars  2 , Florence Porcheret  1 , Véronique Frémeaux-Bacchi  3 , Emma Allain-Launay  1 , Camille Debord  4 , Manon Denis  5   6 , Yann Péréon  7 , Christine Barnérias  8 , Isabelle Desguerre  8 , Gwenaëlle Roussey  1 , Sandra Mercier  6   9
Affiliations
Case Reports

Fatal thrombotic microangiopathy case following adeno-associated viral SMN gene therapy

Julia Guillou et al. Blood Adv. .

Abstract

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 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.

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Figures

Figure 1.
Figure 1.
Clinico-biological characteristics of TMA. (A) Trends in platelet and LDH levels during hospitalization. Eculizumab was administrated at days 13, 19, and 40 after onasemnogene abeparvovec infusion. (B) Peripheral smear shows 6% schistocytes (arrows) at D12 (original magnification, ×50). (C) TMA diffuse skin damage.
See this image and copyright information in PMC

References

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