Surprisingly Common Findings of Cerebral Folate Autoimmunity in Autism©

We have been evaluating autoimmunity to cerebral folate receptors and related transport mechanisms in children with autism.  While the results are early and not fully tabulated – we are surprised by frequency of positive cases.  Certainly it is more than 50% of the cases we send to Professor Quadros’ laboratory at SUNY- Downstate.

Traditionally, cerebral folate deficiency is thought to present with: mental retardation, motor and gait abnormalities, abnormal movements, low motor tone, developmental delays, speech problems, seizures and often times a small head (microcephaly). These symptoms intersect many of the symptoms observed with cases of autism spectrum disorders (ASD), and particularly in cases of Rett Syndrome (RS is a type of ASD) they are nearly the same and it could easily be confused.

We don’t use is it as a routine biomarker yet, but in the refractory or complicated cases it is an important clue that is largely overlooked in autism.

Unlike the traditional description of cerebral folate deficiency, these cases of autoimmunity to the folate receptors present with significant variability ranging from profoundly effected to only mild changes.

Treatment consists of using 1-2mg/Kg/day of body weight of folinic acid – usually as the prescription medicine: Leucovorin®. However, this does not always result in improvement by itself, and we speculate that some form of immune treatment may needed as well.  In support of this concept, researchers have found a milk-free diet downregulates the autoimmunity (makes it less of a problem). This may partially explain why dairy-free diets are helpful for some children with ASD.

Certainly, this is an important area of emerging research which will require more investigation to fully understand.  In the meantime we still find it a useful biomarker in an important subset of children with ASD.

Here are some links to learn more about cerebral folate autoimmunity.

Jeff Bradstreet, MD, MD(H), FAAFP   (321) 259-7111

About Dr Bradstreet
Dr Bradstreet is a graduate of the University of South Florida College of Medicine and received his residency training at Wilford Hall USAF Medical Center. He is a Fellow of the American Academy of Family Physicians. He is an Adjunct Professor at the Southwest College of Naturopathic Medicine in Arizona. He is extensively published in the peer-reviewed literature on subjects of autism, oxidative stress, mitochondrial disorders, virology, hyperbaric oxygen, and toxicology (especially heavy metal chelation). He is trained in the the isolation and use of stem cells.

17 Responses to Surprisingly Common Findings of Cerebral Folate Autoimmunity in Autism©

  1. nanaymiriam says:

    hi dr. bradstreet, if we are going to remove milk/casein from the diet of autistic children how about their oral (teeth) health? As per Dr. Price, children and adults need raw milk/butter/cheese from grain fed cows to ensure remineralization of teeth. How does this coexist with the GFCF diet? I am asking because I think I have autistic tendencies or autistic like symptoms due to mercury toxicity (more like the ASperger’s syndrome)..


    • It really comes down to providing adequate levels of Vitamin D3 since calcium is so readily available in most foods. Calcium can be easily supplemented but I don’t think most children who are getting adequate D3 require anywhere near what the old RDA implies.

  2. Jackie says:

    My son is dairy free and I find that he gets more than enough calcium from leafy green veggies 🙂 Sometimes I mix them in smoothies or sauces, soups, desserts and so on. Pasteurized milk has most of the vitamins cooked out of it, and certainly the enzymes are lost as well. If you choose to include dairy in your diet, why not try it raw?

  3. Laura says:

    Dr. Bradstreet,

    My son was found to have folate binding autoantibodies thru testing by Dr. Quadros. A year later his binocular vision deficiencies have completely resolved, he is much more social and able to keep friends, and he now says when he reads a book, he can make the pictures in his head, and he now enjoys reading. He has been on 25 mg of Leucovorin. It has been an amazing peice of the puzzle.

    FYI, my son is HF Aspergers, ADHD, and Mito dysfunction, etc… in addition, while my son has not been tested for it, we know I have a single mutation on the MTHFR gene.

  4. Desiree Byrne says:

    I have two children with duplications of 15q with mito deficiencies (at this time presumed secondary to the 15q) and cerebral folate deficiency (high blocking antibodies per Quadros and low 5-mthf in spinal fluid). Both are milk/casein free due to documented allergies. The youngest, age 6, is now on 50 mg. of leucovorin twice daily (more classically autistic in presentation though atypical in presentation-improvement so far is slight). My eldest, age 12, is on 25 mg. of leucovorin twice daily (HF asperger’s though again atypical in presentation-tremendous improvement). I wonder why the difference in response?

  5. Desiree Byrne says:

    At the moment, we’re leaning towards something systemic as our doctors feel they’ve ruled out “environmental” causes (many symptoms in place from day 1, no heavy metal toxicity, food allergies addressed, have been fully vaccinated but neither child had even moderate fever with any vaccinations–still some question as to whether the vaccines “took” even, diet heavily controlled/monitored for both–eldest has reactive hypoglycemia and testing in progress for MEN2 youngest is on modified-Atkins to help with myoclonus type ictal events–possible reason for not seeing improvement is seizure, sleep/apnea addressed). Systemically, no one is yet addressing their IgG deficiency. Our hematologist feels that a great deal of their ongoing issues may be centered on something auto-immune or metabolic that has not yet been identified. Its very, very confusing. Every day, another system shows signs of break down (my eldest started having ictal events a couple of weeks ago–and has never had them before).

  6. Crystal says:

    Hi Dr. Bradstreet,

    I’ve been reading with great interest about CFD for ASD children. My child tested positive for blocking antibodies .27 and I tested positive for binding .29. We commenced treatment with methylfolate at 1mg/kg. My child had a week of improved speech and language followed by a rapid decline all around. My child ended up looking more autistic than ever and became quite aggressive and unhappy. We stopped the treatment after 4 weeks, but sadly my child did not return to the higher level of functioning, happiness and nonaggressive state that he was in prior to methylfolate. Can treatment with methylfolate do permanent damage? He has been off for 5 months and till no return to the baseline functioning. I also was treated with methylfolate and enjoyed a good mood and increased energy and clarity for almost two months, then experienced a rapid increase in anxiety in the evening. It continued to worsen, but I did not make the connection with methylfolate until I had a hallucination (no history of any such thing ever in my life). I quickly went off Deplin and returned primarily to normal within a month’s time. Any insight into this?

    If you are an adult and have antibodies is it necessary to forgo milk products? WHat would happen if you added them back in?

    • This is an interesting reaction – concerning for sure – but it must be telling us something. I generally start the children off on very low dose methylfolate or leucovorin. It may be that the changes were too fast = too much too soon. Also these are relatively low levels of antibodies. I hope you have discussed this with your doctor.

      • crystal says:

        I have discussed it with our doctor, who decided that it must just be yeast/bacteria overgrowth, however; after treatment for that the regression remains. It has been months now and we are not back to baseline. I agree that it must be telling us something, I just wish I knew what. Do you ever do consultations for people? I would love to hear some of your thoughts, ideas and avenues to pursue as we try to get back on track. Things were going pretty well before this treatment, it seems like we must be able to get back there! Also, given that the antibody levels are low, is it even worth treating? Thank you!

      • Of course I do consultations and it is even easier to do that with you and your local doctor directly.

    • From the research at SUNY Downstate it seems milk products are the strongest inducers of the this cross reactive antibody – so yes anyone with the antibodies should refrain from Dairy.

  7. Do you have a practice here in Arizona? if so and you are accepting new patients, could you please provide your contact info for scheduling a consult?

  8. shamim says:

    Recently we started active folate from vrp 800mcg only. today I was looking for some answers as we are going through a very hard time now. He is constantly tapping, banging, running, on the go,hitting his brother and others. Could it be linked to active folate?

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