Autism

Leucovorin (Folinic Acid) and Autism: What Parents Should Know

Recently, the U.S. Food and Drug Administration (FDA) announced a new labeling step for leucovorin (folinic acid).

It is now recognized as a treatment option for individuals with cerebral folate deficiency (CFD) who also have autism-related symptoms.

This is an important step forward, but it is not the same as a general FDA approval for autism.

1. What does this mean?

Leucovorin is now FDA-recognized for autism features in patients with CFD. It is not yet approved as a treatment for all children with autism.

2. How strong is the evidence?

Research so far is promising but limited. Small studies suggest leucovorin may improve speech, communication, and social interaction in some children with autism, particularly if they have certain folate-related biomarkers. More large studies are still needed.

3. What about insurance coverage?

Because the label now includes autism features in CFD, insurance (including Medicaid) may begin covering leucovorin in this setting. Coverage will not be immediate and may vary by plan. Off-label use may still be denied.

4. Is testing needed?

Cerebral folate deficiency is identified by measuring the level of 5-MTHF in the cerebrospinal fluid, which requires a lumbar puncture (spinal tap) to obtain the sample.

For Cerebral Folate Deficiency (CFD), two key blood antibody tests are often used to screen for autoimmune causes of the condition:

-Folate receptor alpha (FRα) blocking antibodies
-Folate receptor alpha (FRα) binding antibodies

Testing for folate receptor autoantibodies (FRAA) or related biomarkers may help identify who benefits most. However, these tests are not always covered by insurance. There is only one CLIA* certified lab that performs this test and there are several labs showing up that offer testing but they are not CLIA certified. 

5. What should parents expect?

Leucovorin is not a cure for autism. Some children may see improvements in speech, behavior, or social interaction, but responses vary. It should be used under medical supervision with ongoing behavioral and educational supports.

In summary: leucovorin is a promising option for a subgroup of children with autism linked to folate metabolism, but it is not yet a universal treatment for all children with ASD.

There is not enough data to understand long term side effects of using the medication. 

*A CLIA-certified lab means the laboratory is certified under the Clinical Laboratory Improvement Amendments (CLIA) — a federal law in the U.S. that ensures accuracy, reliability, and timeliness of lab test results.