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

被引：82

作者：

Guillou, Julia ^{[1
]}

de Pellegars, Alice ^{[2
]}

Porcheret, Florence ^{[1
]}

Fremeaux-Bacchi, Veronique ^{[3
]}

Allain-Launay, Emma ^{[1
]}

Debord, Camille ^{[4
]}

Denis, Manon ^{[5
,6
]}

Pereon, Yann ^{[7
]}

Barnerias, Christine ^{[8
]}

Desguerre, Isabelle ^{[8
]}

Roussey, Gwenaelle ^{[1
]}

Mercier, Sandra ^{[6
,9
]}

机构：

[1] Univ CHU Nantes, Ctr Hosp, Nantes, France

[2] CHU Angers, Federat Pediatrie, Angers, France

[3] Hop Europeen Georges Pompidou, Assistance Publ Hop Paris, Serv dImmunol, Paris, France

[4] CHU Nantes, Lab Dhematol, Nantes, France

[5] CHU Nantes, Paediat Intens Care Unit, Nantes, France

[6] Univ Nantes, Ctr Natl La Rech Sci CNRS, Inst Natl La Sante & La Rech Med INSERM, Inst Thorax, Nantes, France

[7] CHU Nantes, Univ Hosp,Filnemus,Euro NMD, Reference Ctr Neuromuscular Disorders, Atlantique Occitanie Carathes AOC, Nantes, France

[8] Necker Enfants Malad Hosp, Reference Ctr Neuromuscular Disorders Filnemus Eu, Assistance Publ Hop Paris APHP, Paris, France

[9] CHU Nantes, Ctr Reference Malad Neuromusculaires AOC, Serv Genet Med, Nantes, France

来源：

BLOOD ADVANCES | 2022年 / 6卷 / 14期

关键词：

HEMOLYTIC-UREMIC SYNDROME; SPINAL MUSCULAR-ATROPHY; ONASEMNOGENE ABEPARVOVEC; SOLUBLE C5B-9; CFI GENE; BIOMARKER; VARIANTS; ONSET;

D O I：

10.1182/bloodadvances.2021006419

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：4266 / 4270

页数：5

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