Friday, 16 October 2015

It’s not Autism, it’s Sotos Syndrome – and more about GABA therapies

I recently returned from a 25 year class reunion; of the 200 or so class members about 120 turned up. Of the 200 we know that at least 5 have a son with autism and at least one has a nephew with autism.  So I had my first ever “autism lunch” discussing all those tricky issues we are left to deal with.

What was immediately apparent was how different each child’s “autism” was and that none of them were the autism-lite variants that are now being so widely diagnosed in older children. or even adults .  Of the six, two are non-verbal, one is institutionalized, yet one talks a lot.  Three sets of parents are big ABA fans and one child did not respond to ABA.

You may be wondering about that high incidence of autism.  This was not a gathering of science boffins or mathematicians; this was at a business school.  One thing is obvious, you can correlate some autism incidence with educational level.  You can connect all sorts of measures of IQ to autism, from having a math prodigy in the family, to having professors at Ivy league type Universities, particularly in Mathematics.  It does appear to be true that the so-called clever genes are also associated with some types of autism.

I presume that if my science-only university organized such events the incidence of autism would be even higher.

On the way back home we met an acquaintance at the airport, who was telling us all about his son with Sotos Syndrome.  "It is not autism", we were informed, but then I am not quite sure what is.  When you look it up, many of the symptoms look just like autism.  In fact, it is a single gene dysfunction that leads to gigantism and various elements of autism.

This brings me to the painting above of Peter the Wild Boy; it is not me I should point out.  The above Peter was a German boy who came to live in England in the 18th Century; he was non-verbal and is now thought to have had Pitt Hopkins Syndrome.  Like Sotos, this is another very rare single gene disorder.

We have already come across Rett Syndrome, which for some reason is treated as autism.

Fragile X is thought of as a syndrome where autism can be comorbid.

Timothy Syndrome is fortunately extremely rare, but I have already drawn on it in my own research into autism.

There are also autism related disorders involving multiple genes.

Prader–Willi syndrome  is a rare genetic disorder in which seven genes (or some subset thereof) on chromosome 15 (q 11–13) are deleted or unexpressed (chromosome 15q partial deletion) on the paternal chromosome.  If the maternally derived genetic material from the same region is affected instead, the sister Angelman Syndrome is the result.

The most frequent disorder caused by known multiple gene overexpression is Down Syndrome.  We saw in earlier post that DS is caused by the presence of all or part of a third copy of chromosome 21.  This results in over-expression of some 300 genes.

Why So Many Syndromes

Even before the days of genetic testing, these syndromes had been identified.  How could that be?  Each syndrome is marked by clear physical differences.

These physical differences where used to identify those affected.

Within autism too, sometimes there are physical differences.  Big heads, small heads, slim stature or heavy stature, advanced bone age or retarded bone age.

So many syndromes , but no therapies

Many of the rare syndromes have their own foundations funding research, mainly on the basis that if there is a known genetic dysfunction there should be matching therapy somewhere.

As of today, there are no approved therapies for any of these syndromes.

The Futility of Genetic Research?

A great deal of autism research funding goes into looking for target genes.  The idea goes that once you know which gene is the problem you can work out how to correct it.  There are numerous scientific journal dedicated to this approach.

Since no progress has been made in treating known genetic conditions leading to “autism”, is all this research effort well directed?  Some clever researchers think it is not.

All I can do is make my observations from the side lines.

What do Down Syndrome, Autism and Pitt Hopkins Syndrome all have in common?

In at least some of those affected, they have the identical excitatory-inhibitory imbalance of GABA, that can be corrected by Bumetanide.

If you did whole exome genetic testing on the responders with these three conditions you would not find a common genetic dysfunction; and yet they respond to the same therapy.

I am actually all for continued genetic research, but those involved have got to understand its limitations, as well as its potential.

More on GABA

This post returns to the theme of the dysfunctional GABA neurotransmitter because the research indicates it is present in numerous of the above-mentioned conditions. 

·        Autism
·        Fragile X
·        Rett Syndrome
·        Down Syndrome
·        Neurofibromatosis type 1
·        Tourette syndrome
·        Schizophrenia
·        Tuberous sclerosis complex (TSC)
·        Prader-Willi syndrome
·        Angelman Syndrome

Based on feedback to me, we should add Pitt Hopkins Syndrome to the above list.

The GABA dysfunction is not the same in all the above conditions, but at least in some people, Bumetanide is effective in cases of autism, Down Syndrome and Pitt Hopkins Syndrome.  I suspect that since it works in mice with Fragile-X , it will work in at least some humans.

GABAA has already been covered in some depth in this blog, but I am always on the lookout for more on this subject, since interventions are highly effective.  It is complicated, but for those of you using Bumetanide, Low Dose Clonazepam, Oxytocin and some even Diamox, the paper below will be of interest.

Regular readers will know that in autism high levels of chloride Cl inside the neuron have been shown to make GABA excitatory rather than inhibitory.  This leads to neurons firing too frequently;  this results in effects ranging from anxiety to seizures and with reduced cognitive functioning.  Therapies revolve around reducing chloride levels, this can be done by restricting the flow in ,or by increasing the flow out.  The Na+/K+/Cl cotransporter NKCC1  imports Cl into the neuron.  By blocking this transporter using Bumetanide you can achieve lower Cl within the neuron, but with this drug you also affect NKCC2, an isoform present in the kidney, which is why Bumetanide is a diuretic.  Some experimental drugs are being tested that block NKCC1 without affecting NKCC2 and better cross the blood brain barrier. 

The interesting new approach is to restore Cl balance by increasing KCC2 expression at the plasma membrane.  This means increasing the number of transporters that carry  Cl  out of the neurons.

In the Modulation of GABAergic transmission paper there is no mention of acetazolamide (Diamox) which I suggested in my posts could also reduce Cl, but via the AE3 exchanger.  This would explain why Diamox can reduce seizures in some people.

The paper does mention oxytocin and it does occur to me that babies born via Cesarean/Caesarean section will completely miss this surge of the oxytocin hormone.  This oxytocin surge is suggested to be key to the GABA switch, which should occur soon after birth when GABA switches from excitatory to inhibitory.  In much autism this switch never takes place.

That would suggest that perhaps all babies born via Caesarean section should perhaps receive an artificial dose of oxytocin at birth.  This might then reduce the incidence of GABA dysfunctions in later life, which would include autism and some epilepsy.

Indeed, children born by Caesarean section (CS) are 20% more likely to develop autism.

Conclusions and Relevance  This study confirms previous findings that children born by CS are approximately 20% more likely to be diagnosed as having ASD. However, the association did not persist when using sibling controls, implying that this association is due to familial confounding by genetic and/or environmental factors.

So as not to repeat the vaccine/autism scare, the researchers do not say that Caesarean section leads to more autism, rather that the kinds of people who are born by Caesarean section already had an elevated risk of autism.  This is based on analysing sibling pairs, but I do not entirely buy into that argument.  They do not want to scare people from having a procedure that can be life-saving for mother and baby.

If you look at it rationally, you can see that the oxytocin surge at birth is there for an evolutionary reason.  It is very easy to recreate it with synthetic oxytocin.

Another interesting point is in the conflict of interest statement:-

Laura Cancedda is on the Provisional Application: US 61/919,195, 2013. Modulators of Intracellular Chloride Concentration For Treating An Intellectual Disability

Regular readers will note that in this blog we have known for some time that modifying GABAA leads to improved cognitive function.  I even suggested to Ben-Ari that IQ should be measured in their autism trials for Bumetanide.  IQ is much less subjective than measures of autism.


My conclusion is that while genetic testing has its place, it is more productive to look at identifying and treating the downstream dysfunctions that are shared by many individual genetic dysfunctions.

By focusing on individual genes there is a big risk of just giving up, so if you have Pitt Hopkins Syndrome, like Peter the Wild Boy, it is a single gene cause of “autism” and there is no known therapy.  Well it seems that it shares downstream consequences with many other types of autism, so it is treatable after all.

I also think more people need to consider that cognitive dysfunction (Intellectual Disability/MR) may indeed be treatable, and not just via GABA; so good luck to Laura Cancedda.


  1. Hi Peter, what do you think about the role of autoimmunity in autism or immune disorders? regards, Valentina

    1. Hi Valentina, in autoimmunity the body in effect attacked itself, like in Crohns disease and rheumatoid arthritis. Studies shown an increase in autoimmune disease in parents/grandparents of children with autism. I characterize my son's autism as being associated with an over-activated immune system. In other words his body over-reacts to minor immune attacks. Is this come kind of brain autoimmunity? You certainly could look at it that way. It seems that reducing this over-response is the key to some people's autism. But different things seem to work in different people, making it very difficulty to draw broad conclusions. It is no suprise that many people with ASD have asthma and older relatives have thyroid disorders, diabetes and arthritis.

    2. One recent study suggested excess antioxidants (endogenous or otherwise) retards the immune system and increases the spread of cancer since the immune system uses reactive oxygen species for killing bacteria, cells infected by viruses, as well as killing cancer cells, not to mention repairing damaged tissues from injury including strenuous exercise. Perhaps this is one of the vectors of antioxidants like NAC helping those with autism, rather than the conventional theory that reducing oxidative stress is solely responsible for improving ones symptoms. Just a contrarian viewpoint that I thought of that I don't necessarily believe myself (I think oxidative stress itself is one of the core problems in autism that correlate strongly with autism severity).

      There are many other ways of globally downregulating the immune system (rapamycin for example), but often with unintended side effects that are not good to have long-term as there is little sense in modulating auto-immunity with immunosuppressors if your child has to be a bubble boy the rest of their life.

      There was a paper I read a year or so ago that I can't remember the details off the top of my head, but that the group was working on a vaccine for allergies and immune disorders by targeting some specific novel proteins they found that help mount an exaggerated immune response.

  2. Peter, I agree, this minor immune attacks are playing a key role causing his body overreaction, it seems that addressing microglia could be a solution, what would you use apart from the classic supplements like probiotics and mct ?regards, Valentina

    1. Hi Valentina, the first thing to note is that there are vast variations within what is diagnosed as autism.

      The chart above shows that only in a minority of cases is IL-6, a key inflammatory cytokine, greatly elevated. In most people it is normal. It would be very useful to measure this. If it is normal then inflammation is quite likely not an issue, at least at the time of the blood test.

      If you are in the smaller group with moderately to severely elevated IL-6, there clearly is a problem, for 10% it is very big problem. Note that for 60% Il-6 is normal.

      Research using minocycline to reduce microglial activation in autism did not show much improvement. But in the people with normal IL-6 you might not expect an improvement. If you are in the 10% with highly elevated IL-6, then minocycline might well have an impact.

      You can also reduce microglial activation with PPAR gamma agonists, this includes Ibuprofen and the flavanol tangeretin (sold as a supplement called Sytrinol). I think in the 60% with normal IL-6, these therapies would not show any benefit.

      In the study connected to the above chart, they used Luteolin to normalize IL-6, but it takes quite a long time. Many peope try Luteolin / Neuroprotek/Lutimax and most do not seem to see any effect. This study suggests that 60% do not need it.

      So rather than spend lots of time and money on pills, probably better to do a blood test and measure IL-6.

      There are numerous other immunomodulatory therapies (TSO, steroids etc), but quite possibly most people with autism do not have this problem.

    2. Should i measure IL.6 in a common blood test? I have recently done him a blood test and lymphocytes count is normal again. He is on l carnitine since almost 4 months. Children with IL.6 elevated have severe autism or not necessarily?Valentina

    3. IL-6 is a standard blood test. I do not think high IL-6 necessarily means severe autism; it just means autism that can be easily improved by reducing IL-6. So elevated IL-6 will make whatever kind of autism you have worse. People with normal IL-6 probably do not benefit from the numerous "anti-inflammatory therapies" being proposed. I think people with high IL-6 probably have some visible symptoms (allergy, food intolerance etc).

  3. Peter, thanks for bringing some awareness for Pitt Hopkins. I have tried Bumantanide on my son with pitt hopkins who is 4.5... he defniitely reacted to it...I gave him the tiniest bit, (1/8 of a pill) but it made him too hyper...I tired a few times and each time I got the same result? What do you attribute this to? And is there anything I could do to help normalize the effect? Like maybe bumantanide with something else? Would love to hear your thoughts...thank you....

    1. It might be worth trying the tiny dose of clonazepam, as an alternative. The benefit is very similar to that of Bumetanide and its effect is also on GABAa.

      The dose is so small it is hard to administer, but this makes it very safe.

  4. So, just to ask a very personal question, was Monty a C-section baby?

    1. Yes, he was. I should point out that I do not think this is a major causal factor in him having ASD; however if in some cases it is a minor causal factor, then the idea of giving oxytocin seems interesting. The maternity units are already using oxytocin to help start or continue labor and to control bleeding after delivery.

      Autism is primarily genetic, but the numerous environmental factors can be influenced. Avoid maternal stress and inflammation during pregnancy (don't work) and have children while younger (against the trend). I suspect that measuring oxidative stress markers and progesterone level would also be useful.

    2. Have 4 kids. 3 with an autism diagnosis. All were C-Section (first kid was 10 pounds so obstretician suggested C-Section) and once you do one C-Section, all subsequent deliveries need to be C-Section. Also, they all had to deal with gestational diabetes and other things that could of been done much better during the pregnancy in 20/20 hindsight.

      I think the jury is still out on how idiopathic autism manifests itself, even though there is a growing list everyday of causal relationships between genes and their regulation that are associated with ASD's.

      With respect to C-Sections, one needs to ask the question of why was there a C-Section in the first place. If I child is very large to begin with, then that raises their risk of autism as well as having a C-Section as well. The question then goes to why is the child so large and in the case of my children, gestational diabetes tends to produce larger than average babies. So is it the gestational diabetes helping to contribute to autism or the C-Section itself as per the Ben-Ari hypothesis regarding oxytocin and the shift in KCC2 expression following a normal vaginal delivery.

    3. Tyler, you raise interesting questions. I doubt we will ever have definite answers.

      If there was a risk-free add-on to having a C-Section, i.e. a little oxytocin, to replace what would have been received naturally, why not take it? Nobody is ever going to do a clinical trial to prove how it affects ASD or epilepsy incidence. The same is true of numerous possible preventative interventions in medicine. It seems only in the case of cancer are these sometimes followed up, like the use of aspirin to reduce cancer reoccurring.

      In other areas of cancer and also Parkinson's and Alzheimer's, simple cheap ideas are not followed up.

  5. Hi Peter,to add to Tyler´s comment, my son also was born by C- Section and had to deal with gestational diabetes, I will give to nac a second chance for my son, the first time he was unwell, do I have to start with 1800 mg the first day and add methyl b12 500 mg?Valentina

    1. I would just use NAC, without B12 to start with. He should have enough B12 in his system.

    2. 3 times daily would be fine to start with nac or is too much?

    3. It might be possible that there is a specific sub-type of autism caused by gestational diabetes and type 2 diabetes.

      In California 1.3 percent of pregnant women have type 2 diabetes, and 7.4 percent have gestational diabetes, so 8.7% in total. But seems that only onset before 26 weeks of gestational diabetes increases risk of autism. This group is about 1.6%. So about 3% of pregnancies are linked to the circa 50% higher incidence of autism linked to T2/GD. So in all, about 4.4% of ASD in California is linked to maternal diabetes (T2 or GD).

      That is quite a big sub-type that could/should be considered separately.

      Perhaps these 4.4% will respond to the same treatments?

    4. would be incredible that these 4.4 subtype will respond to the same treatment, but the question is if this treatment should be different from the other types of autism. Valentina

    5. There are clear sub-groups in autism trials, so certainly people respond to certain therapies. Some sub-groups are genetically defined, but others may linked by events or the environment. So if you can define your sub-group, you can look at works in other people in the same sub-group. So someone with Fragile X would likely respond to watever helped someone else with Fragile X and not what helped the person with Rett Syndrome.

  6. Peter, I think I have a pretty good idea what was the trigger of my son's autism. I am trying to figure out which meds would address his subtype of autism the best, but I am having hard times understanding all the medical terms and conditions. Maybe you could help me to identify if he is hyper/hypo and what can be done to address it.
    I appreciate your help a lot. It's hard to concentrate with an active and rambunctious boy running around and trying to climb me every 5 seconds ;)

    When I was 7-8 month pregnant I had a flu shot that apparently I had a bad immune reaction to. I had developed pain in my wrists shortly before his birth (arthritis) and I was struggling with it all his first year. Steroids did not help, but I changed my diet and it seemed to keep the symptoms away. But after taking PEA just recently, I realized I still have a problem, because I could feel some warm sensation in my wrists and in other joints, it helped to take the inflammation away.
    I think that was the culprit of my son's problem. He had developed similar to mine autoimmune response to my flu vaccine and this inflammation messed up his developing brain even before he was born. The rest of 24 childhood vaccines "finished him off".
    He was born almost two weeks late, I was induced with oxytocin, but not the c section. Do you think oxytocin would be a good drug to try on him?
    What else would be beneficial in this type of autism (autoimmune disorder)?

    Thanks a lot for your time and for this blog. I wish I had more time and opportunity that read it all, but I am the only person taking care of my son 24-7, and it's hard to focus when he is bothering me all day long. I feel overwhelmed with the volume of the information and it's hard to choose the correct strategy at this point.

    Thank you for your help,


    1. Polly, one way to narrow things down is at the end of the following post:-

      Just look up you son's weight/height and other measurement you have (head circumference) at birth and in the first couple of years; then compare to the standard growth charts. Also the APGAR score. If he was big and strong that may suggest that hyper active pro-growth signalling, if he was small and floppy that might suggest hypoactive as being more likely.

      The approach of that paper is a simplification, you could be hypo on thing and be hyper the other. But it is much better than no approach.

      He is very young and I would be careful not to give him too many things. Oxytocin nasal spray is worth a try.

      For allergies you just need to find what is effective. I would see an allergist/immunologist, not a DAN doctor. You might find a mast stabilizer like Cromolyn Sodium is suggested.

  7. Thanks! Allergies seem to be under control now. I stopped the Periactin and his night time jerking had stopped, thanks God! I am so scared of him getting seizures. He does not have them now, once they start its a totally different game plan. I hope none of the new meds will trigger them, even though it seems like all of those meds have siuzures as a possible side effect. But I will still keep trying them, one at a time. It's better to take a risk and try a new thing, as much as I am against any drugs, that to watch your kid be non-verbal for the rest of his life. I know there are other problems besides speech with our kids, but it seems like without speech it's impossible to teach him anything, he still is not potty-trained, does not eat on his own, he is still acting like a baby and I do everything for him. Usually people teach these things when kids start talking, but our kid never started talking and we are still dealing with all those toddler age problems. I am not pushing him, because his mental health and happiness is more important that potty training and drinking from a cup. But at some point I want him to be a little more independent, and speech would help with that.
    He was growing fast until 2 yo. He was a 100 percentile in hights at the age of 18 months. But he never cared for food, never wanted to nurse as a baby, I had to pump and feed him from the bottle while he was sleeping, he never wanted food and would not eat while awake. Still not interested in food. Which is another reason ABA would not work for him, I can not use snack as a positive reinforcement. He is average hights now, but because of the lack of appetite he is underweight. Periactin was perfect for him, because it is supposed to increase the appetite and also would normalize his sleep. But because of its antihistamine properties, it is dangerous for us to use it right now, as it might trigger seizures. I want to start him on Bumetanide and clonazepam first.
    I am also giving him GHRH injections. Is it a good idea for a kid with a hyper active pro-growth signaling? I am also doing RAS injections that r supposed to balance the hormones. I did not see anything on those, except for better coordination and other physical attributes. He also has this "marble pattern" spots on his skin, all over his body and they seem to go away on these shots. I think they are related to growth hormones and he had those spots all his life. Not sure what they mean. No doctors could ever explain those spots to me.

    Thanks again for your answers! I hope my experience will help someone as well.

    PS I tried to do APGAR once, recently, and he was around a 100. But perhaps I answered incorrectly, as the questions are pretty subjective. Like whether you have a problem with potty training. I answered no, because it's not a problem for me to change him and I never even tried to train him, but now I think they meant if he is trainable or not, I did not try, but I think it would not be easy, because he is non-verbal. I do not want to add stress to him, because stress is one of the factors that increase autustic symptoms and I am trying to avoid it at all cost.

    PPS sorry, I meant not the APGAR score, but the autistic test score was a 100. His APGAR score was perfect, 9 out of 10, both one minute and 5 minutes after the birth. He was born perfectly healthy, easy 7 hour labor. The only problem he never wanted to eat. And still does not.

    1. It is pretty clear he has/had hyper active pro-growth signaling. He fits the "textbook" case of classic autism.

      I think GHRH injections are the opposite of what is needed. I would not use them. In the recent post the researcher suggested Gleevac, which reduces GH levels, but this is rather experimental. It may be late now.

    2. Thanks a lot, Peter! I will stop the GHRH immediately.
      Pantogam has an instant effect on him, so I hope that Bumetanide will help as well. I ordered two more packs from Mexico, they are called miccil there, like you said. Hopefully it will arrive soon.

      Thank you,


  8. This comment has been removed by the author.

    1. Danilo, both Bumetanide and very low lose Clonazepam are safe drugs. Several doctor readers are treating their children with these drugs. Bumetanide will cause diuresis and so you have to add back the lost potassium. So I add 250mg of potassium for 1 mg of bumetanide. You should test potassium levels in his blood. Some people seem to have no drop in potassium.

      The dose of clonazepam is so small the biggest problem is how to give such a small dose. In people who respond to this therapy you have the chance that at slightly above the cognitive enhancing dose you get anxiety. Most people are using about 0.025 mg a day. Since your son is very small I would try even lower perhaps 0.02mg, if you go too low it will do nothing.

      With bumetanide you need to try it for a month to know for sure if it helps. With Clonazepam, if he dose is right, you should see an effect after 3 days (it has a long half-life).

      In the PHS research they are looking at HDAC inhibitors in increase the expression of the TCF4 gene, this is epigenetic therapy. There are several well established HDAC inhibitors:-

      Sodium Butyrate (makes butyric acid in the intestines)
      Sulforaphane (from broccoli sprouts)
      Valproate (used for childhood epilepsy)

      In your position, I would ask my doctor to let me trial valproate syrup. It is given to many kids with autism, even without epilepsy. It might well change TCF4 expression.

  9. Dear Peter,

    Thank you very much for the prompt reply! I'll contact my doctor ASAP!

    Do you know if others with PHS tested these drugs?

    I want going to the doctors, that actually doesn't know anything regarding these protocols, with the much info possible...

    Thanks again.

    1. Danilo, HDAC inhibitors are being trialed in the research model but not yet in humans with PHS.

      There are safe HDAC inhibitors and it seems strange not to test the ones known to be very safe.

      Sulforaphane from broccoli has been trialed in autism by Johns Hopkins. You can buy broccoli powder, I use Super Sprouts brand from Australia, just 2.5ml of powder per day.

      Butyrate (500mg) is used by one reader who finds it has an impact in her son, but he does not have PHS. Butyrate may also help any GI problems that are present. It is sold as a supplement but many clinical trials are using it.

      Valproate is very widely used in autism, but I have no data on its use in PHS. It is sold in a liquid form or children and available very widely.

      Valproate is well understood by many doctors and so quite a good one to trial.

  10. Hi Peter,

    I studied a lot these days and I decided I'm starting this trial with my Son:

    1)Sulforaphane >> I'm preparing fresh broccoli sprouts by hydroponics and combine 20 gr of these with a little bit of Super sprouts powder, because I found an interestin clinical trial that demostrated the high absorbition of Sulforaphane by the combination of fresh and powder broccoli.
    I'm planning to give It to my son once a day, during the dinner.

    2) Butyrade>> I think 500mg per day of sodium butyrate could be sufficient, Btw I found that It half-life is very short (around 5 minuti) so I think to mix the butyrade with 500ml of water ( it is soluble) and give it to drink during all the day.

    The first cycle will be for 2 weeks of treatment with one week of stop.
    Depending from the observed result I will increase to 3-4 week with one of stop or decrease to 1 week plus 1 of stop.

    Peter, do you have any comment or suggestion regard my idea?

    Meanwhile I'm continuing with Q10 and omega 3 AL-ALA-DHA that I used from more than one year.

    Ps: I invite again the father with PTHS son that wrote on 20 october 2015 to share his experience with others, thank you!

    1. Danilo, the plan looks good. I think the actual effect of NaB is from the butyric acid it produces, so I would just take 500mg in one go.

      Here is an interesting paper for you:-

      Butyrate, neuroepigenetics and the gut microbiome: Can a high fiber diet improve brain health?

      To make more butyric acid you can eat sodium butyrate, but you can also increase its production in the colon by eating more fiber and/or adding a bacteria/probiotic that produces butyric acid by fermentation.

  11. Hi there… I had posted last week, but for some reason my post did not come through. I have a five year old son with Pitt Hopkins. He currently takes Minocyline which has helped with focus and attention and cognition, I believe, though difficult to measure since he has been on it since he was about 2 years old -- and since he is non verbal it is difficult to measure such things. Around his 4th birthday… he became increasginly more agitated, much more flailing and flapping and was having a very difficult time going to sleep. Some call this "wired but tired" … we started him on amantadine, an NMDA receptor antagonist as well as a subtle dopamine agonist and saw calm as well as some motor improvement within 3 days. We have tried the Bumentanide… it most definitely had an effect… he was screaming and hyper…. and I used a very very tiny dose. He urinated so much and developed dark circles under his eyes… that it scared me a little… so we took him off. It was clearly having an effect… but not exactly a desired effect. Per peters advice, I very much want to try clonazepam, but have had a hard time getting it. So next we tried the broccoli sprout powder… this also had an effect in increasing vocalizations.. that very day… perhaps 40 minutes or so after he took it… however the taste is strong and getting it down my son was a challenge… so I have ordered the powder in capsule form and am waiting for them to arrive from australia. Just today we started the sytrinol. Very vocal. again, noticeable within 40 minutes or so… he also seemed to have a bit better motor control… very subtle though… so I will continue with that and let you know how it goes. Lastly, my son is on the severe end of the spectrum with regards to stomach issues… every day since he was 2 weeks old we live to make sure he poops regularly. He is on 3 different probiotics, as well as the Miraysian that peter recommended-- I drop 3 of the little tablets in his juice and they dissolve easily! and are virtually tasteless! He also takes Betaine HCl, to increase his stomach acid and senna, a natural laxative to help keep things moving. Stay away from Miralax if you can… I believe in Europe you call it Movicol? It depletes magnesium and, I believe, can play a role in reducing seizure threshold… though Peter would know more about that then me.

    1. Hi anonymous, you can always buy empty caps online (very cheap!!) and fill them with broccoli sprout powder yourself. That is what we do, it saves loads $$££$$

    2. thanks! How much broccoli powder do you put in each cap? What size cap do you use?

    3. We fill 00 cap size, equivalent of about 1/3 of a teaspoon, which we found was the best dosage for our son (once a day for 2-4 days in a row, followed by 2-3 day break). Sorry not sure how much that would be in weight, but you might find your child does better with more or less than that anyway.

  12. Anonymous with 5yo son PTHS = Mr. John Doe.
    Hi John, what about minocyCline? How do you use it on you son? Please explain as much as possible, thanks!

  13. Hi Danilo, minovycline has been trialled in Fragile X and Angelmans... b/c PTHS is so rare, I look to other similar disorders to see what is helping. There is currently a trial of Minocycline going on in Spain for Angelmans... or perhaps it just ended. It is no magic pill, but I have taken my son off of it a few times and each time that faraway empty look in his eyes comes back... as if he is not in there...after 3-4 days without. We dose at 5 mg/ kg. he is 14 Kg so he takes 1.5 50 mg pills a day.

  14. Hi Peter,
    Hi John Doe.

    I just found these articles that seem a very good news!
    Please let me know what do you think about.

    Meanwhile I'm giving Broccoli sprounts fresh+powder and sodium butyrate to my son.. I'll post my first impression next 2-3 weeks of treatments...


  15. Hello John Doe,
    among all the treatments to which I subjected my son, I would advise the cranial sacral massage. Unfortunately mine are empirical observations, but I think it's worth groped; my theory is that by improving the circulation of the cerebrospinal fluid, it will help to purify the spurious produced by the defective TCF4. Please let me know if you need other info.



Post a comment