Onasemnogene abeparvovec is an adeno-associated virus vector-based gene therapy for
spinal muscular atrophy (SMA). Although several cases of
drug-induced
thrombotic microangiopathy due to
onasemnogene abeparvovec have been reported, none has been confirmed pathologically. Here, we present renal histopathologic findings of TMA due to
onasemnogene abeparvovec. On day 5 after receiving
onasemnogene abeparvovec, a 23-month-old girl with SMA type 1 developed
thrombocytopenia,
microangiopathic hemolytic anemia,
liver dysfunction,
acute kidney injury, and
hypertension. She was diagnosed with TMA and received an increased dose of
prednisolone,
antihypertensives,
diuretics, packed red blood cell and
platelet transfusion, a single dose of
eculizumab, 4 cycles of
plasmapheresis, and intermittent and continuous
hemodialysis. Her TMA resolved by day 30. On day 49, renal biopsy was performed. Light microscopy revealed proliferation of glomerular mesangial cells and matrix, with mesangiolysis, endothelial cell swelling, and partial double contours of the glomerular basement membrane. Electron microscopy showed endothelial injury, with edematous changes of the subendothelial spaces and neoformation of the basement membrane, without electron-dense depositions. These findings are compatible with the recovery phase of TMA. One year after
drug administration, her motor function is improved. She can hold her posture against gravity and has neither
dysphagia nor respiratory disturbance, but mild
hypertension persists. Physicians should be vigilant regarding TMA as a severe side effect of
onasemnogene abeparvovec treatment, especially when
thrombocytopenia,
hemolytic anemia, increased
lactate dehydrogenase, or
acute kidney injury is present.