To report a case of TMA in a 6 month-old patient with SMA type 1 after Zolgensma administration.

Zolgensma, an SMA therapy recently approved by the Food and Drug Administration (FDA), is recommended to be administered as a one time 1.1 × 10¹⁴ vector genomes (vg) per kg intravenous dose. The most concerning reported side effects of gene therapy are acute liver injury, increased troponin I and transient thrombocytopenia. TMA has not been previously reported as a side effect.

Case report

A 6 month-old SMA type 1 patient received the recommended dose of Zolgensma. At the time of injection, she had been intubated and mechanically ventilated for respiratory failure for approximately 2 weeks and her vitals were within normal limits. Blood urea nitrogen (BUN) 7 mg/dl; Creatinine (Cr) 0.1 mg/dl; platelets (Plt) 503/ul; hemoglobin (Hb) 10.3 mg/dl. Five days post injection, the patient developed hypertension (140s-150s/80s-90s mmHg), hematuria, proteinuria, acute kidney injury (BUN 52, Cr 0.6), hemolytic anemia (schistocytes on peripheral smear, elevated reticulocyte count of 7.5%, Hb 6.5 and elevated LDH 4208) and thrombocytopenia (Plt < 30,000) all consistent with TMA. Infectious workup was negative; ADAMTS13 activity was normal (92%); DAT was negative; homocysteine was normal; C3 and CH50 were normal but C4 was low at < 8.  The patient was treated with antihypertensives, fluid management, platelet and RBC infusions as well as (starting on the thirteenth day post Zolgensma infusion) 5 cycles of plasmapheresis. TMA resolved and child became normotensive on a single antihypertensive.

Physicians and families should be aware of Zolgensma potentially causing TMA.