Cerebral Folate Deficiency – The biggest puzzle piece yet

I have always had a lot of unanswered questions.  There were a lot of pieces to the puzzle that didn’t seem to make sense until I learned about Cerebral Folate Deficiency and its association with autism.

Cerebral Folate Deficiency (CFD) is a relatively newly identified disorder in which there is low 5MTHF (5-methyltetrahydrofolate) in the CSF (cerebrospinal fluid) but normal 5-MTHF in the blood.  5-MTHF is the bioavailable form of folate.   Folic acid is the synthetic form of folate and supplementing with it can often makes problems worse and not better.  These kids need the bioavailable form of folate.  When there is not enough, developmental delays can occur.  Symptoms can manifest as irritability, poor sleep, gross motor problems, seizures and developmental delay among other symptoms.  It often shows itself in young children and regression is typical.  Often, but not always, these kids have a smaller head circumference and CFD is linked to mitochondrial dysfunction in a subset of children.   Cow’s milk down regulates folate receptor autoantibodies (FRAs), so going dairy free is very important.  Folate receptor autoantibodies (FRAs) block the transport of folate into the Cerebral Spinal Fluid and they are being found at an alarming rate in children with autism.  FRAs, dairy and mitochondrial dysfunction are not the only way that CFD occurs.   There are a number of genetic mutations that affect folate metabolism. 

I also discovered that the mothers of these children often cannot break down folic acid themselves due to genetic reasons.  There are several gene mutations that can lead to this problem.  MTHFR is only one of them.  The mother’s shortage of folinic acid sets up their baby for problems in the womb.  Another noteworthy piece of information is that birth control pills deplete the body of folinic acid, putting young mothers-to-be at a strict disadvantage.

**Please note that taking folic acid, as young pregnant mothers-to-be are advised, DOES NOT help.  In fact, it may make problems worse because these mothers cannot break down folic acid, which is the synthetic form of folate.   Instead these pregnant moms should be taking folinic acid or L-5MTHF.   A few prenatals have now started using the good forms of folate in their prenatals.  Thorne is one such company.

Folate is needed to support the metabolism of purines and pyrimidines which are the building blocks of RNA and DNA.  They also are also very important for cells to make energy properly.  If you are diagnosed with CFD, Leucovorin, a high dose folinic acid, is prescribed because it is a versatile form of folate.

The more I read, the more alarmed I became.  Everything I read was hitting home in a very scary way.  There were so many red flags in both my & my baby’s history.  First I will address what was concerning about my history.

I had trouble getting pregnant for a year after stopping birth control pills.  Finally, I got pregnant at age 28 and I was extremely sick during pregnancy.  I was hospitalized several times and vomited a minimum of 10 times per day until my body gave in and my water broke at 33 weeks old.  She had a grade 4 IVH (Intraventricular hemorrhage) at birth.  Not enough folate could explain this occurrence.

Following my first pregnancy with Marley, I had a miscarriage and then an ectopic pregnancy that ruptured.   Both of these could be attributed to not enough folate.

Then I got pregnant with my second child, Skylar, and at the advice of an applied kinesiologist, I started taking L-5MTHF (the broken down form of folate with a methyl donor attached for better absorption) and I was not as sick.  And the baby did much better!!  I did go into premature labor with her at 34 weeks but she held on until 39 weeks.  Perhaps I was not taking enough L-5MTHF?

When I got pregnant with my third baby, I again took methylfolate (800mcg), felt better but had lots of contractions.  I went into premature labor with him at 29 weeks and was put on best rest until he came at 39 weeks.  He is developmentally fine but has severe food allergies.  Again, Perhaps I was not taking enough L-5MTHF?

More things that are concerning about my folate metabolism: 

I have elevated MCH & MVH, which are indicators of either not enough folate or not enough B12. 

I am FOLR2  +/+ (which will block folate receptors)

I am DHFR  +/- (which converts dihydrofolate into tetrahydrofolate)

I am SLC19A1  +/- (which is a transporter of folate and is involved in the regulation of intracellular concentrations of folate.)

As for my daughter, there is even more reason for concern and more red flags:

As I noted before, my daughter had had a grade 4 IVH (Intraventricular hemorrhage) at birth.  She also has a syrinx in her spinal cord that likely developed in utero as well.  Not enough folate could explain these problems. 

She also has strabismus, which may be attributed to her brain bleed OR it could be attributed to a Cerebral Folate Deficiency.

Marley was an irritable baby and she didn’t sleep well at all.  She slept through the night for the first time at 18 months old, but it still was not consistent….a few days on and several days off.  All red flags for CFD.

At age 3, we started her on L-5MTHF (800mcg) and by the next day, she could walk down steps independently.  She was also having hours long screaming tantruming sessions, which ended with staring spells which we believed to be absent seizures.   They stopped when we started the L-5MTHF.  She has been on L-5MTHF ever since.

When she was age 30 months, the genetics department pointed out that she had an unusually small head and therefore, was a good candidate for Rett’s disease, for which they tested her.  The test came back negative along with a completely normal microarray.  Around this time, she was diagnosed with severe, low-functioning autism.  Low-functioning, regressive autism is a sign of CFD.

Marley also has genetic markers that indicate problems with folate metabolism:

She is FOLR1  +/- (which will block folate receptors)

She is FOLR2  +/- (which will block folate receptors)

She is DHFR r +/- (which converts dihydrofolate into tetrahydrofolate)

She is MTHFR A1298C +/- (which converts 5-MTHF to THF)

She is SLC19A1 +/+ (which is a transporter of folate and is involved in the regulation of intracellular concentrations of folate.)

Add all this to the fact that she fatigues easily, has chronic constipation, has tight muscles on her left side, is still developmentally delayed and has problems with focus and I was concerned.   If she did have CFD, she may start to have seizures once puberty hit.

Since this is a fairly new diagnosis and few mainstream pediatric neurologists know about CFD being tied to Autism, I had to ask around to see what doctor would be my best bet with whom to approach with all this information.  We have seen several neurologists in the past and they have had nothing to offer us at all…..so I wanted to make this appointment count.

If it turned out that she has Cerebral Folate deficiency, she would be prescribed Leucovorin, which is high dose calcium-folinic acid in an effort to bring up her levels of L-5MTHF in her CSF.

I was in luck.  I live in a city with great medical resources and a fabulous, well-known hospital and there just happens to be a pediatric neurologist on staff that knows about and understands CFD and it’s link to Autism.  I made an appointment.

I don’t have much luck with doctors, but to my surprise and pleasure, he was both wonderful and knowledgeable…….and concerned.  He agreed with all the information I presented to him and said he wanted to do a lumbar puncture right away to rule CFD in or out.  He said to me:

"Kids with autism should have a full neurological and metabolic work-up to see if there is something we can do. Autism is a set of symptoms and if we can find something treatable to help with their symptoms we should do it."

Yes....after taking Marley to see several neurologists and developmental peds over the years who have tried to send us out the door with an antidepressant or an anti-psychotic drug, or GI docs that I had to beg to help my daughter when she was in terrible, excruciating pain.....that afternoon I hit the jackpot.

He listened. He was interested in what I had done to take her this far in her development. He said "if we can find something that is treatable, many of my patients go on to be extraordinary adults. Not just ordinary....but extraordinary because not only are they functioning independently but they have extra gifts to share."

And the appointment was made for a lumbar puncture.

I was terrified.

We went into the hospital early in the morning.  They used Versed & Fentanyl to sedate her, but she is hard to sedate and even with the maximum dosage of both sedatives, she sang to them during the procedure.  

Recovery was hard.  She was in extreme pain for 2 days.  She was dizzy and couldn’t stand.  We had her lie flat on her back & pushed fluids like crazy to get her body to reproduce more spinal fluid to relieve the pressure.  By the 3^rd day, she had excruciating headaches that were relieved only when she laid flat on her back.  I was panicked.  But the neurologist told me that it can take some kids a week to recover and to keep pushing fluids and keep her flat on her back.  I did and by day 5, things were looking up.  She was up and around for about 30 minutes before the headaches set in.   By day 6, there were less symptoms.  By day 9 she was recovered from the lumbar puncture and the waiting game for results began.

We were on vacation when I got the call from the pediatric neuro resident who had done her lumbar puncture.  She said ….

“We have about half of Marley’s results in and everything is normal.”

I was shocked.  I said “Define normal.  Tell me her numbers.”

She told me Marley’s 5-MTHF is a 44 (range 40-120).  I exclaimed, “THAT’S NOT NORMAL! That is very low!  It is HALF of what it should be.  We want her to be between 78-82.  Especially considering she has been dairy free and supplemented with 5-MTHF almost all her life! Look at the study published in 2013 by Dr Frye and Dr Rossingol showing that kids with autism have levels anywhere from low 40’s to 80’s and that combined with FRA’s (Folate receptor autoantibodies) puts them at a huge disadvantage.  See the levels of the kids treated here. They treated these kids with Leucovorin and the kids showed gains in several areas.  See the study here.

The pediatric resident just told me to take my argument to the attending doctor whom we had met originally. I did….and after hearing my argument, he agreed with me that she needed to be treated for Cerebral Folate Deficiency.  I think he is still learning about all of this because I had to tell him the dosage of Leucovorin that is used to treat CFD and he easily agreed with me after trying to prescribe a much lower dose.  The neurologist said to look for increased socialization, less emotional meltdowns, more tolerance to foods (less picky eating) and better gross motor skills with Leucovorin.

All of this information is in the study and in current literature on CFD and Autism Spectrum Disorders and it left me wondering why pediatric neurologists are left in the dark on this subject.    This is a huge break-through in Autism.  And it is TREATABLE!  If caught and treated early enough, Leucovorin can provide significant progress or even a complete recovery of both neurological and ASD symptoms.

In the 2013 study, 93 children were studied for Folate Receptor autoantibodies and they were found in 75% of the children.  FRAs are only one cause of Cerebral Folate Deficiency. From the abstract:  “Given these results, empirical treatment with leucovorin calcium may be a reasonable and non-invasive approach in FRA-positive children with ASD.”

There is only one lab that can measure FRAs in blood and they have recently reopened. However, the ONLY way to test for CFD is with a lumbar puncture.

A great paper on Cerebral Folate Deficiency and Autism 

It has become clear to me that our local pediatric neurologist does not know enough about CFD to treat my daughter appropriately, so I have made an appointment with one of the doctors that actually wrote the study.  He will see her in a few months.  I hope to have her on Leucovorin very soon and report to him how she is doing.  I also know that bringing up 5-MTHF levels in the CSF is a slow process, so I don’t expect over-night results.  Instead I need to look for slow and steady gains. 

I am so hopeful for her future and I will keep you posted on her progress.   

Thank you for your love and support while she continues to heal.

 For even more information on Folate and its association with Autism, click here.

 

Ten tips for a productive trip to your child’s specialist

Doctor or practitioners’ appointments have consumed much of my oldest daughter’s life.  There has been the pediatrician, the ophthalmologist, the pediatric gastroenterologist, several neurodevelopmental pediatricians, pediatric neurosurgeons, several pediatric neurologists and that doesn’t even begin to account for the biomedical doctors and practitioners.  My daughter needs all these doctors to help manage her care…both biomedical and mainstream. 

In my opinion, the best type of doctor to have when your child has autism is a MAPS (Medical academy of Pediatric Special Needs) or a DAN! (Defeat Autism Now!) doctor; however, there may be times when your child needs to see a specialist.

When a child with autism sees a mainstream specialist, I have found there are a lot of things to consider.  Today I am going to talk about how I prepare for meeting with a specialist because it has taken me a long time to learn these lessons myself.  

1.     Ask around to find the most compassionate, knowledgeable doctor in your area. In our case, this doctor needs to be up-to-date with the most recent studies on autism and how it is intertwined with metabolic problems, neurological, immunological and genetic problems.  For example, if you are seeing a pediatric neurologist, you want him/her to know about Cerebral Folate Deficiency in kids with autism.  If you are seeing a pediatric GI, you want them to understand that kids with autism classically have GI distress and you want them to be willing to investigate and treat that.  Knowing what to expect from this specialist is very helpful, so asking other parents that have seen that doctor for their feedback is very helpful.  If you are extra-ambitious, you can read the specialist’s published papers if they have any.  This gives you an idea of where their specific interests lie and how they approach problem areas.

2.  Do your homework.  Research.  This helps you speak the same language as the doctor and  also helps you know exactly what to ask for…which leads us to #3. 

3.     Know what you want from the appointment.  A good doctor will ask “Why are you here and what do you hope to get from this appointment?”  Be ready to answer that question with specific answers.  Be ready to make your argument as to why your child needs testing in your opinion.  Stay away from open-ended questions like “What avenues would be useful to explore?”  Hopefully, you have this information before even stepping into the doctor’s office. If you don’t, a MAPS (Medical Academy of Pediatric Special Needs) or a DAN! (Defeat Autism Now!) doctor can help direct you.  You want to have a set agenda when going into the office.

4.     Make sure that this specialist has access to all of your child’s medical history BEFORE you arrive. Hopefully, the doctor will take the time to review it before he or she even walks into the exam room.

5.     Make a ONE page (not twenty) list of reasons why you are here at this specialist’s office and what you want.  For example, if you want testing for CFD, make a list of the reasons you want this and the child’s history related to this.  For example, the child cannot tolerate milk; the child responds well to methylfolate supplementation with better cognition skills, child has staring episodes, etc.  List as many reasons as you can think of.  And list them as symptoms….NOT as your diagnosis.  For example, if your child has staring episodes…write down “staring episodes” – “Could this be seizures?” (even if you very well know that they could be.)  Make two copies of this.  One to give to the doctor and one for you to refer to as you speak to the doctor.

6.     Make a one-page list of all your child’s medications and supplements and their dosages and give it to the admitting nurse so they can pass it on to the doctor.

7.     Bring any new studies that you think may be relevant to your child’s case.  Since much science is new and emerging in the autism field, sometimes we have to bring in the peer-reviewed studies to show the doctor.  Even if they have already read the studies, this shows the doctor that you have done your homework and you don’t want to waste their time.

8.     Be respectful of their time.  Don’t be long-winded.  Get to the point quickly and accurately.  Answer all questions as honestly as you can.

9.     Stay in their wheelhouse!  Stick to the doctor’s strengths.  That is why you are there after all.  Don’t ask a neurologist questions about candida and don’t expect a mainstream GI doctor to understand why you think MiraLax is bad for your kid because your kid has leaky gut and the plastic in the MiraLax could go right into their bloodstream.  They won’t get it.  Don’t even go there.  You can ask for alternatives to medications (like MiraLax), but don’t go looking for an argument.

10. Lastly, listen to the doctor.  Genuinely listen as a concerned parent.  Don’t roll your eyes or get upset.  If that is how you feel, wait until after he or she leaves to do it.  Don’t argue, regardless of whether or not you agree with what is being said. I don't see anything to be gained by arguing.  Bring up your points and let the doctor tell you his/her thoughts on the matter.

I hope that these quick tips make for an easier trip to the specialists office and I hope you get as much as possible out of the visit.  Good Luck!  

Healing with a Positive Attitude

 I am blessed to be married to an optimistic man.  Every problem (or opportunity) is met with:  “It’s good to have options.”  Or “We can handle this.”  Or “It’s okay to feel how you feel.  Now let’s figure this out.”  His attitude tends to rub off on those around him.

The best advice I ever got when starting on this journey of recovery was to keep a journal.  To keep track of progress.  To see what works and what doesn’t.  To keep a log of your child’s behaviors – both good and bad.  To watch the progress and the setbacks.  The leaps and the regressions because all this knowledge can lead you to the next step.

Recently, I took some time out to review old journals.  They date back almost ten years now.  They are mostly just notes from when I first started giving her supplements.  The first was fish oil.  She was non-verbal then and it was a really tough time.  In my head, I remember how awful it was -- But as I read my journal, I read things like:

11-30-04 (age 2)

“When reading a book that had a baby’s eyes highlighted, she pointed to my eyes.  Did great at TEACCH.  No crying spells and did almost all her tasks!”

12/9/04 (age 2)

“I asked Marley what a ladybug says and she made a squeaking noise!  This is HUGE because she did something on command.  YAY Marley!”

And the entries go on like this…..highlighting all her accomplishments – no matter how very small.  I actually cheered her on in my writing with YAYs and WOWs!

Then I cried as I read about how she gets sicker and sicker.  How I suspected seizures because of the blank stares, flickering eyelids and terrible tantrums followed by a “what-the-hell-happened” look on her face.  Then I started timing the tantrums and noting how long they go on (over an hour each time) and how very violent they are and noting her triggers….being pulled out of the bath tub & changing her diaper could set her off for an hour or longer.

Her bowel movements were sometimes up to 10 per day.  Her poor butt was burning.  Nothing I did could control her unstoppable GI problems and messy stools.

I wrote about how I discovered DMG could help kids with seizures and how I was elated when the DMG stopped her tantrums…..but made her extremely hyper.  I was doing all this on my own.  No one to guide me.  But I recorded all my notes….all the studies I was reading and my heartache when I took her to the neurodevelopmental pediatrician who doubted every last thing I told him about her improvements on fish oil and DMG. 

But then I found a new doctor and the happy, positive entries came back:

4/8/05 (age 2 ½)

2^nd day of methylfolate and no DMG & new diet with no white sugars or white flours and only two pieces of fruit per day.   For the first time today, at Little Gym, she stopped when the teacher said, “Freeze”.  She did this THREE TIMES.  Awesome!  She also began to walk on the balance beam with me holding her hands. YAY!

4/20/05

Changes since adding methylfolate (FolaPro) Chris and Nana both notice more babbling, good spirits and generally happy and starting to walk down stairs. Go baby!

I was cheering her on in my writing again.  With every successful intervention, I got more and more excited.  You can see it in my writing.  “I can do this….she CAN get better” was the sentiment. Little by little, I gained more confidence as I could see her slowly, slowly blooming.  There were lots of lows along the way but we just kept plugging along and what I learned was….Attitude is EVERYTHING.

If you want something, go get it.  Hire a good doctor that will stand behind you.  You are going to hit bumps in the road…but without the bumps, the little things are not worth as much.  This journey is not what I wanted for myself (or anyone else), but I have learned so much.  I have learned the importance of the right foods.  I have learned that the body can heal itself if given the right tools.  I have learned that you have to fight for what is right.  I have learned to follow my intuition.  I have learned that love is there…even in the darkest hours.  I have learned to trust the man I love because he has got my back.  And I have learned that it is all about attitude.  Being grateful everyday for your blessings is essential. 

So be grateful.  Be mindful.  Be positive.  You can do this.

***This post is dedicated to the Steffens family who have made positive thinking an art.  They taught my husband how it is done and he taught me.  And to my father-in-law, who would have celebrated his 69^th birthday today.  I love you.  And attitude IS everything. ***

“The longer I live, the more I realize the impact of attitude on life.  Attitude, to me, is more important than education, than money, than circumstances, than failures, than successes, than what other people think or say or do.  It is more important than appearance, giftedness, or skill.  It will make or break a company…a church…a home.  The remarkable thing is we have a choice everyday regarding the attitude we embrace for that day.  We cannot change our past…we cannot change the fact that people act a certain way.  We cannot change the inevitable.  The only thing we can do is play on the one string we have, and that is our attitude…I am convinced that life is 10% what happens to me and 90% how I react to it.  And so it is with you…we are in charge of our ATTITUDES.”  -Chuck Swindol, Author of “Attitude.”      

Diet changes alone won't heal leaky gut

Two years ago, we put my middle daughter on a gluten free, casein free, soy free diet and within a week she was better.  No more chronic headaches.  No more complaining of tummy aches.  No more bedwetting.  No more scary night terrors.  And her picky eating was so much better.  Clearly food was a problem for her.  And I thought I had fixed it.  I gave digestive enzymes for about 6 months into her new diet.  But she was so much better I dropped the digestive enzymes but continued with this diet.

Fast forward two years.  Now she is in second grade and is a funny, smart, active sensitive kid.  However, this past Fall, she started complaining of daily headaches.  The kind of headaches that took her to the school nurse daily.  The kind of headaches that made her sensitive to light and she didn't want to eat.  And at the same exact time, she started wetting the bed again.  She had not done this in two years with the exception of the time that she accidentally ingested gluten. 

After two weeks of this, I made an appointment with the eye doctor.  When there are chronic headaches in a child – the first thing I think about is vision problems.  The eye doctor said she has 20/20 vision but her eyes “relaxed” when he gave her a weak prescription for up-close reading, so we ordered her some reading glasses.  While we waited on the glasses, I took her to the chiropractor.  He adjusted her and her headaches went away only to return two days later.

In my heart, I knew there was more to it-- especially because she was wetting the bed again.  So, I made an appointment with our integrative allergist and ENT who can do IgE (true food allergy) and IgG (food sensitivity) testing.  While waiting for the allergist appointment, the glasses came in.  Unfortunately, there was no change in her headaches when wearing her glasses.  There’s $200 down the drain.

With my girl still suffering, we finally got in to see the doctor.  He ran a food IgE panel and an IgG food sensitivity panel.  He also ran an environmental IgE blood test.  The IgE food allergy testing came back clean but she came back with loads of IgE environmental allergies (which we already knew about). 

The IgG food sensitivity testing came back next.  I expected it to be better than two years ago but it was not.  Now she is reacting to the foods in her new diet.  This can only mean one thing.  Her leaky gut is not healed.  Changing her diet alone was not enough. 

Back to the drawing board I went.  Looking for the perfect combination of supplements to heal her leaky gut and make those terrible headaches go away, I settled on L-Glutamine twice per day to seal her GI tract, IgG 2000DF to provide aggressive immune support and very strong probiotics (stronger than her daily probiotics) to repopulate the gut with good flora.

And amazingly, within two days of the new supplement protocol the headaches went away.  And so did the bed-wetting.  She was back to her normal self -- able to play soccer again and no longer at the nurse’s office daily.  I kept her on this regime for a month. That is the amount of time it takes to heal the average leaky gut.  However, if it is severe, it could take longer. 

Leaky gut has many symptoms and they can vary from person to person.  It may present as gas or bloating.  It may present as reactions to foods including rashes, headaches or just plain not feeling right after eating.  And food sensitivities are a delayed response.  The can occur up to 72 hours after ingesting the food.  Leaky gut has also been shown to cause depression because it allows bacteria to enter the bloodstream.  Another thing to consider is that leaky gut is caused BY inflammation and it causes inflammation in the body – which can lead to autoimmune diseases or disorders.

L-Glutamine works very fast to heal the gut lining.  See study here.  However, following a gluten free, dairy free, soy free and low sugar diet is your first line of defense against leaky gut.  Once you have your diet in place, you can use many things to heal the GI tract.  Homemade bone broth works well because of the gelatin.  Deglycyrrhizinated licorice helps to repair the intestinal lining.  Aloe leaf extract and slippery elm bark can both reduce inflammation and sooth the GI lining.  So, there a host of options to help seal the GI tract and reduce inflammation.

Thanks for reading about our journey.  I am forever learning how to keep my kiddos healthy! 

Here's my girl, now EIGHT years old....happy again!