Genetic susceptibility to thrombotic microangiopathy in a 10-month-old patient with SMA type 1: a caveat for gene therapy eligibility.
Rossella D'Alessandro, Alessandra Somà, Martina Vacchetti et al.
✦ AI-curated · Sources linked
Case in brief
A 10-month-old girl with spinal muscular atrophy type 1 was initially deemed eligible for gene therapy with onasemnogene abeparvovec. However, baseline assessments revealed undetectable Complement Component 3 levels and multiple infections. Genetic testing identified likely pathogenic variants in the C3 gene and uncertain significance variants in the CFI gene, leading the multidisciplinary team to withhold therapy to prevent thrombotic microangiopathy.
What made this case unusual
The case underscores the importance of genetic screening for complement deficiencies in patients with SMA prior to gene therapy, as it revealed a significant risk for thrombotic microangiopathy.
Diagnostic / clinical pearl
Clinicians should consider complement screening in patients with spinal muscular atrophy before gene therapy to identify those at risk for thrombotic microangiopathy.
Why it matters
This case emphasizes the need for careful genetic evaluation in therapeutic decision-making, potentially preventing severe complications associated with gene therapy.