Thrombotic microangiopathy can be a severe side effect of onasemnogene abeparvovec (Zolgensma®) treatment, which physicians should be vigilant about, according to a new study published in Neurology. They should be especially attentive if thrombocytopenia, hemolytic anemia, increased lactate dehydrogenase, or acute kidney injury is present researchers advised.

Onasemnogene abeparvovec is an adeno-associated virus-based gene therapy approved by the US Food and Drug Administration (FDA) to treat all types of spinal muscular atrophy (SMA) in patients aged up to 2 years. It has been shown to be safe and effective in a number of clinical trials, but can cause serious adverse events.

Here, a team of researchers from Japan led by Takashi Hamazaki, MD, reported the case of a 23-month-old female patient with SMA type 1 who developed thrombocytopenia, microangiopathic hemolytic anemia, liver dysfunction, acute kidney injury, and hypertension 5 days after receiving onasemnogene abeparvovec. 

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After being diagnosed with thrombotic microangiopathy, the patient was treated with high-dose prednisolone, antihypertensives, diuretics, and a single dose of eculizumab. She also received a packed red blood cell and platelet transfusion, 4 cycles of plasmapheresis, and intermittent and continuous hemodialysis, which resolved her condition by day 30.

Nineteen days later, she underwent a renal biopsy, which was analyzed by light and electron microscopy and showed findings compatible with the recovery phase of thrombotic microangiopathy. 

In spite of the side effects, onasemnogene abeparvovec did improve the patient’s motor function. “She can hold her posture against gravity and has neither dysphagia nor respiratory disturbance,” the researchers wrote, “but mild hypertension persists.”

Onasemnogene abeparvovec works by providing the body with a healthy copy of the SMN1 gene, which is mutated in patients with SMA but is essential for the production of enough functional SMN protein, without which motor neurons die. 


Yazaki K, Sakuma S, Hikita N, Fujimaru R, Hamazaki T. Child neurology: pathologically confirmed thrombotic microangiopathy caused by onasemnogene abeparvovec treatment for spinal muscular atrophy. Neurology. Published online March 29, 2022. doi:10.1212/WNL.0000000000200676