Leucovorin

Leucovorin, also known as folinic acid, is a synthetic form of vitamin B9 that is only available by prescription. Until recently, it was mainly used in patients with cancer, but its use is now being studied for the treatment of cerebral folate deficiency (CFD), a rare condition that can be associated with certain autism-related symptoms.

CFD occurs when the brain does not receive enough folate, even if blood levels are normal. Folate is essential for brain growth and function. A deficiency can lead to developmental delays, difficulties with language and communication, seizures, or other neurological problems. It can also result in behaviors and symptoms similar to those seen in autism. The causes of CFD can include:

- Genetic factors, such as mutations in the FOLR1 gene.
- Autoimmune factors, where the body produces antibodies that block folate from entering the brain (this is the most common form).

When blocking antibodies are present, symptoms can resemble those of autism. Leucovorin can bypass these blockages and deliver the active form of folate directly to the brain. According to studies published up to 2024, approximately 85% of children with CFD show improvement in at least one area, particularly in communication and language. Side effects are generally mild, including agitation, headache, insomnia, or increased aggression in about 10% of cases.

At present, the exact relationship between CFD and autism is not fully understood, nor is the proportion of autistic individuals who may have CFD. Some studies suggest that in certain cases, CFD could influence the development of autism, particularly in individuals with language difficulties or higher support needs. However, it is important to note that CFD is very rare and not all autistic individuals have it.

To determine whether a child has CFD, doctors can perform:

- A lumbar puncture, which measures folate in the cerebrospinal fluid.
- A blood test (FRAT), which detects blocking antibodies.

When these tests are not feasible, physicians may trial treatment with leucovorin and closely monitor progress.

Despite promising results, research agrees that more studies are needed to confirm the efficacy and safety of leucovorin in autistic populations. Therefore, leucovorin is not a universal treatment for autism and should only be used under medical supervision in children with confirmed CFD or folate-blocking antibodies. Regular folate supplements are not a substitute and could even be harmful.