Treatable Cause of Refractory Seizures in an Infant with a Novel Mutation

Area of Science:

• Genetics
• Neurology
• Biochemistry

Background:

• Pyridoxine-dependent epilepsy (PDE) is an inherited metabolic disorder.
• It is typically caused by mutations in ALDH7A1 or PNPO genes.
• Early diagnosis and treatment with pyridoxine are crucial for managing PDE.

Observation:

• A 5-month-old infant presented with severe, refractory seizures.
• Brain MRI results were normal.
• Clinical exome sequencing identified a novel mutation in the PROSC gene.

Findings:

• The infant showed a remarkable clinical response to pyridoxine treatment, becoming seizure-free.
• This case represents the first report of a PROSC gene mutation associated with PDE in India.
• The identified genetic variant in PROSC is considered rare.

Implications:

• This finding expands the known genetic spectrum of PDE.
• It underscores the importance of genetic testing, including novel genes like PROSC, in diagnosing refractory epilepsy.
• Highlights the potential of pyridoxine therapy in cases with PROSC mutations.