Do you or your child have an autism spectrum disorder? Do the symptoms include a language delay or other language disorder? Have you done genetic and other medical testing, but have not yet found a cause for the autism?
If you answered yes to all of these questions, you may want to consider testing for Folate Receptor Alpha Autoantibodies (FRAAs). Links with info about this test are at the bottom of this post. Emerging research indicates that FRAAs can cause autism spectrum disorders with language impairments. FRAA testing is potentially important because for people who test positive, there is a treatment that can improve or even eliminate autism symptoms. The best part is the treatment is just high doses of folinic acid, a B-vitamin similar to folic acid (but there is a difference, and it matters!). Folinic acid has an excellent safety profile, and is available in lower doses over the counter, and in higher doses as a prescription called Leucovorin.
So what are FRAAs? Your immune system is constantly producing antibodies to fight off foreign invaders like bacteria and viruses. Antibodies are why when you get a cold, it doesn’t last forever and eventually you get better. However the system is not perfect, and sometimes (for unknown reasons) the immune system produces antibodies that attack parts of your own body, creating problems. These are called autoantibodies. Autoantibodies sometimes show up in healthy people, but high amounts of certain autoantibodies can cause diseases collectively known as autoimmune diseases. These diseases span a wide range of problems, but they share a common cause: your immune system fighting a healthy part of your own body. For example, I have autoimmune hives. This means my body produces autoantibodies that attack my own skin, causing itchy rashes that look like an allergic reaction (but the allergen is my own skin). Rheumatoid arthritis and Lupus are other examples of autoimmune diseases.
Emerging research in the last decade indicates that for some individuals with ASD, there is an underlying autoimmune cause. Specifically, FRAAs are autoantibodies that attack Folate Receptor Alpha, and they come in two flavors called blocking and binding. Folate Receptor Alpha’s job is to transport folate across the blood-brain barrier and into the brain. Folate is critical for brain development, and folate starved brains can show autistic symptoms and delayed language development. Too little folate in the brain is called Cerebral Folate Deficiency (CFD), the symptoms of which overlap with ASD. In children with ASD, language delay, and no identified genetic cause, around 60-75% test positive for FRAAs. 20-30% of their parents will also test positive. In one study, control children who had developmental delays but not ASD tested positive only 3% of the time. The good news is, a different form of folate called folinic acid can get around this problem. Folinic acid does not require Folate Receptor Alpha to cross into the brain, instead it can be carried by something else called the Reduced Folate Carrier (RFC). This path isn’t as efficient, but high doses of folinic acid have been shown to increase folate levels in the brains of people with FRAAs. In a recent randomized, double-blind, placebo controlled clinical trial (gold standard in medicine) significant improvements were seen with high dosage folinic acid in children with ASD and FRAAs in the areas of reduced stereotypical behavior, increased attention, and increased receptive, expressive, and non-verbal communication abilities compared to controls who received placebo treatment. This result is considered preliminary though, because the trial included less than 50 children.
There is a blood test for FRAAs. However, it is currently not approved by the FDA for clinical use, and is considered research use only. That said, you can order the test for yourself or your child. It is not covered by insurance, and costs $200. It takes around 4-6 weeks to get results. Leucovorin (high dose folinic acid) is also not (yet) approved to treat ASD. The usual use for Leucovorin is for chemotherapy patients, because it reduces the negative effects of the chemotherapy drugs. Don’t let that scare you though, Leucovorin is still just folinic acid, a B-vitamin. Excess folinic acid is processed by the kidneys and excreted in the urine, so it should be very safe as long as the individual has healthy kidneys. However, the long term safety of Leucovorin for ASD treatment has not yet been studied. The Leucovorin dosage used in the clinical trials to treat children with ASD is 2mg/kg body weight, up to a max of 50 mg, for 12 weeks. Children started at half that dose for the first two weeks, and doses were divided in two (1/2 given in the morning, 1/2 in the evening). The results after 12 weeks are very promising, but full effects take 1-3 years. Treatment may need to be lifelong.
Folate levels are usually tested with blood tests, which will not detect this problem because the issue is not the folate level in the blood, but rather the inability of that folate to get to the brain. The only way to truly know the folate level in the brain is to do an invasive spinal tap. So if your doctor says you don’t need FRAA testing because your blood shows adequate folate levels, your doctor is wrong (this happened to me). Studies indicate though that patients can skip the spinal tap, and if blood tests are positive for FRAAs, it is probably safe to assume the spinal tap would show low folate levels and proceed to treatment.
If you have read this far, you have probably guessed by now that I had my daughter tested for FRAAs. She is positive for the blocking type, at high levels. We began Leucovorin treatment this week. This is the end result of months of fighting for this, including switching doctors to find someone willing to order the test and prescribe the treatment. The Leucovorin is now being compounded every two weeks, special for her, by the hospital pharmacy. I am now going to test myself as well, because lower levels of FRAAs can cause other symptoms including anxiety, pregnancy complications, and preterm birth (kiddo was preterm). I wrote this explanatory PSA post after reading almost a dozen medical papers on this topic and personally reviewing the evidence. I found it so compelling that I fought hard to make this happen for my daughter. Now I’m hoping I can spread this info and help other people as well. Like most ASD treatments, Leucovorin treatment is more effective the younger the patient is when they start it, so don’t delay!
Below are links with more info for anyone who wants to pursue this testing and treatment for themselves or their child:
Interview with doctor leading this research that explains it well: http://www.nofone.org/dr-frye-q-and-a-folinic
Information on the FRAT test to detect FRAAs: http://iliadneuro.com/Information-on-Frat.html
Clinical trial reports: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3578948/