A 10-year-old girl developed serious seizures that wouldn’t stop, even with multiple medications. Doctors discovered she had a rare genetic condition where her brain couldn’t properly absorb folate (a B vitamin). A simple genetic test identified the problem—a mutation in a gene called FOLR1 that acts like a broken door preventing folate from entering the brain. Once doctors gave her a special form of folate called folinic acid, her condition improved dramatically. This case shows how genetic testing can unlock the mystery behind hard-to-treat seizures and lead to life-changing treatments.

The Quick Take

  • What they studied: Why a young girl developed severe, treatment-resistant seizures and how doctors finally found and treated the underlying cause
  • Who participated: One 10-year-old girl who had normal development early in life but started having seizures after age four
  • Key finding: A genetic mutation prevented her brain from absorbing folate properly, and treating her with folinic acid (a special form of folate) significantly improved her seizures
  • What it means for you: If someone has seizures that don’t respond to standard medications, genetic testing might reveal a treatable cause like this folate transport problem. However, this is a rare condition, so it would only apply to a small number of people with hard-to-control seizures

The Research Details

This is a case report, which means doctors documented the medical story of one patient in detail. The girl was evaluated by neurologists who noticed her seizures weren’t responding to typical seizure medications. They ordered genetic testing called whole exome sequencing, which reads the instructions in a person’s genes to find problems. This test discovered a mutation in the FOLR1 gene—the gene that makes a protein responsible for transporting folate across the blood-brain barrier (the protective filter that controls what enters the brain). Once they identified the problem, doctors prescribed folinic acid, a form of folate that can bypass the broken transport system and reach the brain directly.

Case reports are important because they describe unusual situations that doctors might not see often. By documenting this girl’s journey, doctors can help other physicians recognize similar patterns in their own patients. This case demonstrates that genetic testing should be considered when seizures don’t respond to standard treatments, as the cause might be a rare genetic condition rather than a typical seizure disorder.

This is a single case report, which is the lowest level of scientific evidence. It tells us what happened to one person, but we can’t assume the same treatment will work for everyone with similar symptoms. The strength of this report is that it includes genetic confirmation of the diagnosis and documented improvement with treatment. However, we would need studies with many more patients to confirm how common this condition is and how well this treatment works overall.

What the Results Show

The 10-year-old girl had normal development until age four, when she began experiencing seizures. Over time, her seizures became more frequent and severe, and she didn’t respond to multiple antiepileptic medications—drugs that typically control seizures in most people. Doctors performed genetic testing and discovered a mutation in the FOLR1 gene, which normally produces a protein that acts like a door, allowing folate to enter the brain from the bloodstream. With this mutation, that door was broken, so folate couldn’t reach her brain even though she had normal folate levels in her blood. Once doctors started treating her with folinic acid (a form of folate that can reach the brain through alternative pathways), her condition improved significantly. Her seizures became more controlled, and her neurological symptoms improved.

The case highlights that cerebral folate deficiency (CFD) is a condition where the brain specifically lacks folate, even if blood tests show normal folate levels. This is why standard blood tests might miss this diagnosis. The FOLR1 gene mutation is one specific genetic cause of CFD. The case demonstrates that genetic testing, specifically whole exome sequencing, was essential for identifying the root cause and guiding treatment.

This case aligns with existing medical knowledge about FOLR1-related cerebral folate deficiency, a rare genetic disorder. Previous research has shown that folinic acid supplementation can help patients with this condition, but cases are uncommon and often diagnosed late. This report reinforces that genetic testing should be considered earlier in patients with treatment-resistant seizures, potentially leading to faster diagnosis and better outcomes.

This is a single case report, so we cannot determine how common this condition is or how well this treatment works across different patients. We don’t know the long-term outcomes—whether the girl’s improvement continued over months and years. We also don’t have information about whether other patients with the same FOLR1 mutation respond similarly to folinic acid treatment. Case reports cannot prove cause-and-effect; they can only suggest possibilities that need to be tested in larger studies.

The Bottom Line

For patients with seizures that don’t respond to standard medications: Consider genetic testing to identify rare genetic causes (moderate confidence). For those diagnosed with FOLR1-related cerebral folate deficiency: Folinic acid supplementation appears to be an effective treatment (based on this case and existing medical literature). Patients should work with a neurologist and genetic specialist to determine if genetic testing is appropriate for their situation (strong recommendation).

This finding is most relevant to: Children and adults with treatment-resistant seizures; Families with a history of seizure disorders; Neurologists and genetic counselors evaluating difficult-to-treat seizures. This is NOT relevant to people with typical seizure disorders that respond to standard medications, or to people without seizure disorders.

Based on this case, improvement in seizure control appeared to occur relatively quickly after starting folinic acid treatment, though the exact timeline isn’t specified. Long-term benefits would need to be monitored over months and years. Individual responses may vary.

Want to Apply This Research?

  • If diagnosed with FOLR1-related cerebral folate deficiency, track seizure frequency and severity weekly (number of seizures, duration, time of day) alongside folinic acid dosage and timing to identify patterns and treatment effectiveness
  • Set daily reminders for folinic acid supplementation at the same time each day; log any changes in seizure patterns, energy levels, or neurological symptoms to share with your healthcare provider at appointments
  • Maintain a monthly summary of seizure trends, medication adherence, and symptom changes; schedule regular check-ins with your neurologist (every 3-6 months) to review data and adjust treatment as needed; track any side effects or new symptoms that emerge

This case report describes one patient’s experience with a rare genetic condition. It should not be used for self-diagnosis or self-treatment. If you or a family member experiences unexplained seizures or neurological symptoms, especially if they don’t respond to standard treatments, consult with a qualified neurologist or genetic specialist. Genetic testing should only be performed under medical supervision. The treatment and outcomes described in this case may not apply to other individuals. Always follow your healthcare provider’s recommendations for diagnosis and treatment.