Your child was developing normally, then something changed. Speech slowed down. Motor skills stalled. Behaviors shifted. If you’ve been told your child might have cerebral folate deficiency, or you’ve come across the term while researching autism, you probably have a lot of questions. This guide covers what CFD is, how it’s diagnosed, and what treatment looks like.
The Short Answer
Cerebral folate deficiency (CFD) is a condition where the brain doesn’t get enough folate, even when folate levels in the rest of the body are normal. It typically appears around age two and can cause developmental delays, speech problems, seizures, and autism-like symptoms. CFD is treatable with a prescription medication called leucovorin, which delivers folate to the brain through an alternate pathway. Early diagnosis and treatment tend to produce the best outcomes.
What Is Cerebral Folate Deficiency?
Folate is a B vitamin that plays a critical role in brain development and function. Your body uses it to make DNA, produce red blood cells, and support the nervous system. In most people, folate travels from the bloodstream into the brain through a transport system called the folate receptor alpha (FRα).
In children with CFD, this transport system is disrupted. Folate can’t get into the brain the way it normally would, so even though blood folate levels may look fine on standard lab work, the brain is starving for it.
There are two main causes:
Genetic CFD happens when a child has a mutation in the FOLR1 gene, which controls how the folate receptor works. This is rare but well-documented.
Autoimmune CFD happens when the body produces antibodies (called folate receptor alpha autoantibodies, or FRAAs) that physically block folate from binding to the receptor. This form is more common and has been found in a significant percentage of children with autism.
What Are the Symptoms of CFD?
Symptoms usually start appearing around age two, though the timeline can vary. Because many symptoms overlap with autism, ADHD, and other developmental conditions, CFD is often missed or misdiagnosed.
Common symptoms include:
- Delayed speech or loss of previously acquired language
- Developmental regression (losing skills the child had before)
- Difficulty with movement and coordination
- Seizures (in roughly one-third of cases)
- Irritability or behavioral changes
- Problems with social interaction
- Repetitive behaviors
- Intellectual disability
- Difficulty with sensory processing
One important thing to understand: CFD symptoms don’t always look the same in every child. Some children have severe regression, while others have milder delays that are harder to identify. This is part of why it often goes undiagnosed.
How Is CFD Related to Autism?
CFD and autism are not the same condition, but they overlap in significant ways.
Research has found that folate receptor alpha autoantibodies are present in roughly 58% to 76% of children on the autism spectrum. That doesn’t mean all of those children have CFD, but it suggests that impaired folate transport to the brain is far more common in children with autism than in the general population.
For some children, what looks like autism may actually be driven, at least in part, by folate deficiency in the brain. In those cases, treating the underlying folate problem with leucovorin can lead to meaningful improvements in symptoms like speech, social engagement, and behavior.
This is why the FDA recently moved to expand the leucovorin label to include CFD with autistic features. You can read more about that in our article on leucovorin and autism.
How Is CFD Diagnosed?
Diagnosing CFD can be challenging because there’s no single, simple test that confirms it in every case.
The gold standard is a lumbar puncture (spinal tap) to measure levels of 5-methyltetrahydrofolate (5-MTHF) in the cerebrospinal fluid. If 5-MTHF levels are abnormally low while blood folate levels are normal, that points to CFD. However, this test is invasive and not always practical, especially for young children.
Blood testing for FRAAs can detect the antibodies that block folate from reaching the brain. This test is less invasive than a spinal tap and is available through specialized labs. However, the American Academy of Pediatrics notes that there are currently no FDA-cleared or approved tests for FRAAs, and the results should be interpreted carefully alongside other clinical information.
Genetic testing can identify mutations in the FOLR1 gene and other genes involved in folate metabolism. At MindWell, we offer genetic testing as part of a comprehensive evaluation process. While pharmacogenetic testing like GeneSight is focused on medication response, it provides valuable insight into how your child’s body processes different treatments.
Clinical evaluation — a thorough psychiatric evaluation is always an essential starting point. Your provider will review your child’s developmental history, symptoms, any previous test results, and the overall clinical picture before recommending next steps.
How Is CFD Treated?
The primary treatment for CFD is leucovorin, a prescription form of folinic acid. Unlike regular folic acid supplements, leucovorin is already in an active form and can bypass the blocked folate receptor by using an alternate transport route called the reduced folate carrier (RFC).
Here’s what treatment typically looks like:
Starting treatment: Your provider will determine the right dose based on your child’s age, weight, and symptoms. There’s no universally standardized dosing protocol yet, but published research has used doses ranging from 0.5 to 2 mg/kg per day.
Monitoring: Most providers recommend continuing treatment for at least three to six months before evaluating effectiveness. During this time, you’ll track changes in speech, behavior, social interaction, and any side effects.
What to expect: Improvement isn’t overnight. Some families notice changes within a few weeks, but for many, progress is gradual over months. Research suggests that children who start treatment earlier tend to have better outcomes.
Side effects: Leucovorin is generally well tolerated. The most commonly reported side effects in studies include increased agitation, insomnia, headache, and tantrums. Serious adverse effects have not been attributed to leucovorin in autism-related research.
Important: Over-the-counter folate or folic acid supplements are not a substitute for leucovorin. They use a different pathway and will not effectively bypass a blocked folate receptor. Taking high-dose folate supplements without medical guidance could be harmful.
You're Doing the Right Thing by Searching for Answers
If you’re reading this, chances are you’ve already been through a frustrating process. Maybe your child has been evaluated multiple times. Maybe you’ve tried different treatments with mixed results. Maybe you’re just now hearing about CFD and wondering if it could explain what you’ve been seeing.
Whatever brought you here, the fact that you’re looking into this is a good thing. CFD is still underdiagnosed, and many families don’t learn about it until years after symptoms start. The more you understand about it, the better equipped you are to advocate for your child.
How MindWell Can Help
MindWell Psychiatric Services offers leucovorin consultation for families exploring this treatment option. Our approach starts with a full psychiatric evaluation to understand your child’s symptoms, followed by genetic testing when appropriate, and ongoing medication management to monitor progress and adjust treatment as needed.
We accept Medicaid, Medicare, TRICARE, and most major insurance plans. Self-pay options are available for families without coverage.
When Should You Take the Next Step?
If your child has experienced developmental regression, speech delays, or autism-like symptoms, especially if previous treatments haven’t worked as expected, a conversation about CFD and leucovorin may be worth having.
Schedule an appointment with MindWell Psychiatric Services. We’ll help you understand whether this path makes sense for your child.
FAQs
Can CFD be cured?
CFD caused by autoantibodies is treatable with leucovorin, and many children show meaningful improvement. However, it’s typically a long-term treatment rather than a one-time fix. Children with genetic forms of CFD may need ongoing supplementation.
Can adults have CFD?
Yes. While most research focuses on children, adults can also have impaired folate transport to the brain. Symptoms in adults may include brain fog, depression, fatigue, and cognitive difficulties. If this sounds familiar, it’s worth discussing with a psychiatric provider.
At what age should CFD be evaluated?
Symptoms typically appear around age two. If your child is showing developmental regression or speech delays at any age, evaluation is appropriate. Research suggests that earlier treatment leads to better outcomes.
How much does leucovorin treatment cost?
Cost depends on your insurance coverage. Once the FDA label change is finalized, Medicaid and CHIP will be required to cover leucovorin for CFD. Many private insurers already cover it. MindWell can help you verify your benefits before starting treatment.
Does my child need a spinal tap to be diagnosed?
Not necessarily. While a lumbar puncture is the most definitive test, blood testing for folate receptor autoantibodies and genetic testing can provide useful information without the invasiveness. Your provider can help determine the right approach.
Is cerebral folate deficiency the same as folate deficiency?
No. Standard folate deficiency means the body doesn’t have enough folate overall. CFD specifically means the brain isn’t getting enough folate, even when levels elsewhere in the body are normal. Standard blood tests may not catch CFD.
