Folate receptor autoantibodies (FRAA) bind or block the receptors that allow folate to cross the blood brain barrier. These antibodies have been found to be elevated in 70% of children with autism resulting in low levels of folate within the brain. Because folate is critical for multiple physiologic systems associated with neurodevelopment it can easily be seen how low levels of folate within the brain would result in symptoms associated with autism. The symptoms of cerebral folate deficiency secondary to folate receptor autoantibodies include:
High dose folinic acid (0.5–2 mg/kg body weight) has been shown to bypass these antibodies and improve verbal communication in children with autism. Parents have the option to test for the presence of folate receptor antibodies through a blood draw or do a trial of high dose folinic acid. The pharmaceutical version of high dose folinic acid is Leucovorin and can be prescribed by a physician. It's available as tablets and can be compounded into a liquid by a compounding pharmacy. Folinic acid is also available over-the-counter as a supplement but typically in lower doses per tablet requiring multiple tablets per day to achieve a high dose.
Another important aspect of treatment is strictly avoiding all sources of animal-derived milk products including those from cow, camel, goat and sheep. Research has shown that milk proteins can trigger an immune response in the gut that results in the presence of these folate receptor antibodies.
- seizures
- cerebellar ataxia (sudden, uncoordinated muscle movement)
- dyskinesia (involuntary movement)
- developmental regression
- low muscle tone
- sleep disturbances
- lack of speech development
High dose folinic acid (0.5–2 mg/kg body weight) has been shown to bypass these antibodies and improve verbal communication in children with autism. Parents have the option to test for the presence of folate receptor antibodies through a blood draw or do a trial of high dose folinic acid. The pharmaceutical version of high dose folinic acid is Leucovorin and can be prescribed by a physician. It's available as tablets and can be compounded into a liquid by a compounding pharmacy. Folinic acid is also available over-the-counter as a supplement but typically in lower doses per tablet requiring multiple tablets per day to achieve a high dose.
Another important aspect of treatment is strictly avoiding all sources of animal-derived milk products including those from cow, camel, goat and sheep. Research has shown that milk proteins can trigger an immune response in the gut that results in the presence of these folate receptor antibodies.
Studies:
Folate Receptor Alpha Autoantibodies in Autism Spectrum Disorders: Diagnosis, Treatment and Prevention
"Autoantibodies against folate receptor alpha (FRα) are present in about 70% of the children with a diagnosis of ASD, and a significant number of these children respond to oral folinic acid with overall improvements in speech, language and social interaction."
"Autoantibodies against folate receptor alpha (FRα) are present in about 70% of the children with a diagnosis of ASD, and a significant number of these children respond to oral folinic acid with overall improvements in speech, language and social interaction."
Folinic acid improves verbal communication in children with autism and language impairment: a randomized double-blind placebo-controlled trial
"Thus, in this small trial of children with non-syndromic ASD and language impairment, treatment with high-dose folinic acid for 12 weeks resulted in improvement in verbal communication as compared with placebo, particularly in those participants who were positive for FRAAs."
"Thus, in this small trial of children with non-syndromic ASD and language impairment, treatment with high-dose folinic acid for 12 weeks resulted in improvement in verbal communication as compared with placebo, particularly in those participants who were positive for FRAAs."
Video Lecture:
Testing:
The following lab processing centers are not contracted with FRATNow but are familiar with FRAT testing. We recommend you contact your local branch of either of these processing centers to ask if this test can be done for your child with the kit you bring to them before taking your child for a blood draw.
Treatment:
Leucovorin is the pharmaceutical form of folinic acid that comes in tablets. It's much more concentrated than over-the-counter supplement capsules. It reduces the number of tablets given per day to two instead of multiple capsules per day of the supplement. The tablets can be crushed and mixed into food, applesauce, juice etc.
If your insurance will not cover the cost of Leucovorin and you have to pay out-of-pocket we recommend that you use GoodRx.com to check for the best price in your area.
Leucovorin can also be compounded into a liquid formula through Lee Silsby Pharmacy. Please discuss with your physician the cost of doing this before the prescription is initiated.
If your insurance will not cover the cost of Leucovorin and you have to pay out-of-pocket we recommend that you use GoodRx.com to check for the best price in your area.
Leucovorin can also be compounded into a liquid formula through Lee Silsby Pharmacy. Please discuss with your physician the cost of doing this before the prescription is initiated.
