Autism, a Dynamic Encephalopathy, Indeed

 

With a title like that, not many people will stumble upon this post with Google.

So, for the hard-core of readers, today I am going to develop an idea of Martha Herbert, the pediatric neuroscientist from Harvard, who writes a lot about autism.

Incidentally, most researchers do not like publicity, and particularly those looking at autism.  Martha, herself makes some side remarks as to why this is; as I suggested in earlier posts it dates back 10+ years to a certain Dr Wakefield.

“A further barrier to considering the body’s impact on the brain was the reaction to the work of Wakefield, who argued not only that there was a link  between  autism  and  vaccines  but  also  that  this  link was mediated through the gastrointestinal system. For the better part of a decade any attempt to discuss gastrointestinal or immune issues with autism was construed as a support of Wakefield’s vaccine hypothesis, and it was difficult to discuss, let alone get funding for, clinical or research observations about these problems.  One way around the essentially taboo character of somatic problems in autism was to treat them as coincidental symptoms. For example, one could  talk about gut problems provided one made  it clear that they did not cause the autism in the brain. Improvement after treatment of gut problems, which is often observed, would then be explained as a consequence of reduction of pain and discomfort, but not of any direct impact on core brain mechanisms generating autistic behaviors.”

Another fearless autism researcher, not shy to voice his opinions by blog and tweet, is Paul Whiteley, in Sunderland.   Paul is very much a believer in the role the gut/diet in autism, he and Paul Shattock are the driving force behind the gluten and casein free diet as a therapy for autism.  Given what Martha writes above, and the association between Shattock and Wakefield, is it surprising that the GCF diet remains on the fringes?  I know some parents who wholly endorse it.

Here is a link to one of Martha’s recent works, for Herbert fans:-

From Static Genetic Brain Defect to Dynamic Gene- Environment- Modulated Pathophysiology

Dynamic Encephalopathy

It was Martha who called autism a dynamic Encephalopathy.  Encephalopathy just means a brain disease.

What she means is that over time autism changes, day to day and year to year.  Just as during fever, autism symptoms may wane, other environmental provocations may cause flare ups.  With age come hormonal changes that will inevitably change the central hormonal homeostasis, I hope for the better, as generally is the case.

Other than being a fancy word, Encephalopathy, is probably a much better word than autism.  There are many types of Encephalopathy and there are multiple causes, it refers to a syndrome of global brain dysfunction; this syndrome can have many different organic and inorganic causes.  As with autism the hallmark of encephalopathy is an altered mental state.

 
Forget Autism think Encephalopathy

If you have not already opened up Wikipedia, I suggest you do.

http://en.wikipedia.org/wiki/Encephalopathy

From my desk research and primary research, I know that one factor behind this encephalophy is chronic inflammation, otherwise known as neuroinflammation.

At this point, we should look at what neuroscience can tell us about neuroinflammation

The Dana Foundation is a private philanthropic organization committed to advancing brain research.  Founded in 1950 and with $230+ million in assets I think they should be a good source.  Here  is an excellent paper, that is written for non-scientists. 

 Consequences of the Inflamed Brain

Among the many interesting insights are these:- 

 “Until recently the CNS and peripheral immune sys­tem were thought to operate independently.”

“However, new research has led to important advances in our understanding of how immune-related events in the periphery can influence CNS processes, thereby altering cognition, mood, and behavior, and these advances are suggesting that inflammation may have important long term implica­tions for the brain.”

 “Inflammation in the body can lead to inflammation in the brain”

“The same cytokines that participate in produc­ing the inflammatory response in the body also initiate the communication process to the CNS. They accumu­late in the bloodstream and thereby travel to the brain”

“They cross into the brain in regions where the barrier is weak, and they bind to receptors on the insides of the cerebral vascular blood vessels, thereby inducing the production of soluble mediators within the epithelial cells that can cross into the brain.”

“In addition, there are neural as well as blood-borne communication routes. For example, there are cytokine receptors on nerves, such as the vagus, that innervate peripheral immune organs, and these nerves communicate to the brain and are activated during infection.”

“During a normal infection, neuroinflammation and the resulting adaptive sickness behaviors persist only for several days. However, if these responses become exaggerated or prolonged, the outcomes may well become estab­lished, leading to cognitive impairment instead of brief memory disruption,”

 “… physiology can become pathology when a set of processes designed to be rela­tively brief becomes prolonged.”

“However, peripheral inflammation is highly complex and involves many immune cells and their products. Existing anti-inflammatory drugs often target only one of these. For example, non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, inhibit only a hor­mone, prostaglandins, leaving other actors in inflam­mation (cytokines, chemokines, etc.) untouched.”

“A second way that central neuroinflammation could be prolonged is less obvious. The CNS may come to over-respond to the same signal from the peripheral immune system. As noted above, microglia and the cytokines they produce when activated are at the core of the neuroinflammatory response that pro­duces sickness behaviors. If microglia were to become “sensitized,” which means they respond in exagger­ated or prolonged fashion, then sickness behaviors would become intensified and prolonged—pathology instead of physiology.”

“Most encouragingly, studies in numerous animal models show that the development and expression of chronic pain can be blocked with drugs that inhibit either microglial activation within the spinal cord, or the inflammatory cytokines that microglia produce.”

“In addition, microglia also can become sensi­tized without a prolonged peripheral inflammation. For example, aging appears to sensitize microglia so that microglia, particularly in the hippocampus, respond in exaggerated fashion to input. Thus, neuroinflammation produced by surgery, peripheral infection, and the like, is greatly exaggerated in aged subjects. Correspond­ingly, aging also augments the chances of depressive behaviors, cognitive impairments, and pain produced by peripheral inflammatory events. Encouragingly, however, some human studies show that inhibition of microglia and cytokines in the brain blunts such patho­logical outcomes.”

“Blockade of inflammation in the periphery and microglial activation/cytokine action in the CNS, may well become important therapies for a range of disorders not often thought of as mediated by these factors.”

Conclusion

There is nothing new to me in the Dana paper; this in itself is rather a shock.  If you have followed my blog from the start, you should also not be surprised; but I have never seen quite so much scientific good sense written in just four pages.  It tells me a lot and reassures me that I am on the right track with my cytokine blocking therapies, mast cell stabilization and somewhat far fetched, vagus nerve stimmulation ideas.

There are other science-based "inflammation control" therapies and I will be writing about them later.

P.S.  Why no Dean’s List for Martha?

Regular readers of my blog may have noticed that a small number of the several hundred researchers, whose papers are discussed here, are given a pat on the back and moved to the Dean’s List.  Why not Martha?

There is a good reason.  For many years Martha keeps going on about the “Fever Effect” in autism.  This is the strange phenomenon where autistic behaviours abate during fever, i.e. sickness associated with high temperature.  I myself witness this every time Monty, aged 10 with ASD, has a high temperature.  I think that conclusively solving this, might indeed tell us something profound about this wide phenotype of autism.

I think with the resources of Harvard, she should be able to figure this out.  Her TRANSCEND Program gives her a pool of research subjects.

Peter has just one mouse model of autism and, at the age of 10, he is getting a big to be called a mouse.

So Martha, put aside the MRIs and the calcium channelopathies, if you figure it out before me, you get on the Dean’s List.

If I can prove the underlying reason, I will put myself on the Dean’s List.

 

A Hypothesis: Vitamin D, Calcium, Milk, and the Autism Epidemic

by Seth Bittker

My name is Seth Bittker, and I am the father of a boy with ASD.  My son’s development was slow up until about 2 1/2 years of age.  Around this time, his milk consumption increased, and it began crowding out other sources of sustenance.  Within a few months he regressed, and we received an autism diagnosis soon after this.  Stopping his milk consumption was the first step in helping him get better.

Like some other parents of those with ASD children, I noticed that his behavior varies significantly with what he eats.  When he consumes large amounts of calcium fortified foods or beverages, his behavior gets worse: he becomes more autistic in a behavioral sense.  Since milk has a lot of calcium, and calcium fortified foods do as well, it seemed like there might be some connection to calcium and his symptoms.  Later based on a doctor’s recommendation we gave him supplemental vitamin D.  We did not notice much initially, but a few weeks later he developed hives, and he regressed.  Since supplementation with vitamin D increases absorption of calcium, it appeared that the bad reaction to calcium and vitamin D might be connected.  Based on these experiences and others, I eventually inferred that we should keep him on a relatively low-calcium diet and avoid vitamin D supplementation or fortification (milk as well as many other foods in the US are fortified with vitamin D).

I also concluded that my son was different from most others affected with autism as some have suggested that vitamin D deficiency is involved in inducing autism,[1] and he evidently did not have a deficiency based on the vitamin D trial even though vitamin D levels in his blood were relatively low.

But is he really different than others with autism?  If one examines the evidence from a number of genetic syndromes that are comorbid with autism, in many cases the cause is over-active calcium channels (effectively too much intra-cellular calcium).[2]  You can see this by looking at syndromes such as Timothy syndrome, Williams syndrome, and Sotos syndrome, which have high comorbidity with autism and seem to be caused by too much intra-cellular calcium.  In Williams syndrome the connection is through a gene which upregulates vitamin D.[3]  In some of these syndromes is it well known that supplementation with calcium and vitamin D are contraindicated.[4]

In addition there are certain biochemical markers that are typical in autism, and my son seems to have this same biochemical gestalt.  For example two types of immune system cells released by the thymus are called “Th1” cells and “Th2” cells, and Th2 cell levels relative to Th1 cells are much higher in the blood of those with autism than in controls.[5]  As Th2 is associated with extra-cellular immunity, this suggests that those with autism will be prone to allergies,[6] which fits with anecdotal observation.  In addition with autism we see elevated markers for oxidative stress and endothelial damage.[7]  Also those with autism typically have functional deficiencies of magnesium[8] and potassium.  By functional we mean the levels may not be low in the blood relative to controls, but there is a biochemical need for greater consumption.  To see the latter you can give somebody with autism a small dose of supplemental potassium, and the result is generally a reduction in autistic symptoms.  For more on this, see Peter’s work: http://epiphanyasd.blogspot.com/2013/08/potassium-may-play-important-role-in.html.

It turns out that vitamin D skews the immune system to produce elevated levels of Th2 cells.[9]  One can infer that it also produces functional deficiencies of potassium and magnesium as these minerals offset the effect of calcium on calcium channels and vitamin D increases the absorption of calcium.  In addition in high doses vitamin D causes oxidative stress and endothelial damage as we see in autism.[10]

Oral supplementation with vitamin D can cause other consequences as well.  Supplementation with significant doses of vitamin D early in life, results in more cases of allergies, asthma, and dermatitis later.[11]  Asthma, allergies, and dermatitis all feature high levels of Th2 cells like autism.[12]  Is it too much of a stretch to suggest that supplementation with vitamin D early in life, might result in more cases of autism later as well?

On looking at the data we can see that my son as well as most other babies in much of the civilized world received, and in many cases continue to receive, large oral doses of vitamin D starting from birth.  As a baby we gave him vitamin D drops, and he also occasionally received some formula.  Starting at one year of age he consumed increasing amounts of milk (fortified with vitamin D in many countries) as well as children’s multivitamins, which also contained vitamin D.   Here is a graph showing vitamin D content of various beverages:

 

We are giving babies today much more oral vitamin D than they would consume from human milk alone and also much more than they would have consumed in past decades through formula and food sources when vitamin D fortification was more restrained.  In fact based on nutrition data and caloric intake, a baby just out of the womb consuming Similac baby formula today will receive approximately 855 IU per day of vitamin D.[13]  I am 190 pounds.  If we assume that dose should be proportional to weight, which is a good baseline assumption for most vitamins, I should consume 16,245 IU per day of vitamin D.  This is a huge dose, and based on past experience I know it would have a devastating effect on my health.  Why should it not be the same for some subset of babies?

When and where vitamin D consumption by the young is high, is where autism rates are high.  For example, in the United States autism rates are high relative to much of the rest of the world and they rose gradually starting around 1980 as much of the population transitioned to lower fat milks, which increased consumption of vitamin D.[14]  Later rates rose again in the early 1990s as the amount of vitamin D in milk was increased significantly with no change in the label.[15]  Rates continued rising with the popularization of the Sippy Cup starting in the 1995.[16]  They rose further during the 2000s as the Institute of Medicine increased the supplementation recommendations for babies in 2003 and again in 2008.[17]

When looking internationally, the evidence also points to a role for oral consumption of vitamin D in inducing autism.  Cuba for example has extraordinarily low rates of autism.[18]  The Cuban Health Service does not supply vitamin D drops to babies.  Nor do they fortify milk or other foods with vitamin D in Cuba.[19]  The Amish also have very low rates of autism as well.  They do not provide vitamin D drops to babies, and the milk they consume comes straight from cows: no vitamin D is added.[20]  In the United Kingdom rates of autism are lower than in the United States.[21]  Fortification and supplementation are common in the United Kingdom, but at somewhat lower levels than in the United States.[22]

Vitamin D is also used as a rodenticide, and experiments in rats show that it is more deadly to male rats than female rats.[23]  Is it any coincidence that autism strikes many more males than females?  Babies who get most of their sustenance from formula also receive more vitamin D than those who receive vitamin D from human milk.  Not surprisingly autism rates are higher among those who are formula fed.[24]

Vitamin D’s involvement also explains why some with autism benefit from a “casein” free diet as such diets avoid milk, which has high calcium content and is fortified with vitamin D in many countries.  It also explains why low-oxalate diets are beneficial as well as ketogenic diets.  Oxalates cause excess calcium salts to precipitate in the body and ketones effectively remove excess calcium due to acidity.[25]  Both lower the calcium load.  Oral supplementation with vitamin D also explains why some with autism have a favorable reaction to chelation.  Chelation agents remove excess calcium at the same time as they remove other metals.[26]  So they also lower the calcium load.

So the evidence suggests that over-consumption of vitamin D by babies and toddlers may induce autism in a genetically susceptible subset of the population.  This explains the biochemistry of autism as well as the nature of the autism epidemic.  There are a number of other data points that fit with this hypothesis.  If you are interested in this topic, here is an ebook with a lot more detail: http://www.amazon.com/dp/B00GVB46ES.

I want to thank Peter for allowing me to be a guest blogger here, and I also want to thank you for reading this. How do you view this hypothesis?  Do you have observations that are relevant to it?  Are you aware of existing data that would help confirm it or refute it?

---

[1] http://www.medical-hypotheses.com/article/S0306-9877(07)00537-3/abstract

[2] For more on calcium channels and autism, please see http://www.autismcalciumchannelopathy.com/Genetic_Factors.html.

[3] http://www.ncbi.nlm.nih.gov/pubmed/6977721

[4]  http://www.fpnotebook.com/pharm/Vitamins/VtmnD.htm

 

[5] http://www.ncbi.nlm.nih.gov/pubmed/9627004

[6] http://www.sciencedirect.com/science/article/pii/S1380293397100057

[7] http://www.ncbi.nlm.nih.gov/pubmed/21651783 and http://www.ncbi.nlm.nih.gov/pubmed/16908745.

[8] http://mdheal.org/magnesiu1.htm

[9] http://www.jneuroinflammation.com/content/8/1/56

[10] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052582/ and Gross, David Ross, Animal Models in Cardiovascular Research, p. 316.

[11] http://www.direct-ms.org/sites/default/files/Hypponen%20Vit%20D%20allergy%2006.pdf

[12]http://www.nature.com/jid/journal/v133/n10/full/jid2013148a.html and http://www.ncbi.nlm.nih.gov/pubmed/10919498.

[13] http://nutritiondata.self.com/facts and www.nal.usda.gov/fnic/DRI/DRI_Energy/energy_full_report.pdf.

[14] http://future.aae.wisc.edu/

[15] FDA, M-I-92-13.

[16] http://www.nytimes.com/2013/08/11/magazine/

[17] http://www.ncbi.nlm.nih.gov/pubmed/12671133 and http://pediatrics.aappublications.org/content/122/5/1142.

[18] http://healthimpactnews.com/2013/study-evidence-that-acetaminophen-especially-in-conjunction-with-vaccines-is-a-major-cause-of-autism-and-asthma/

[19] http://www.ncbi.nlm.nih.gov/pubmed/12947458

[20] http://www.ncbi.nlm.nih.gov/pubmed/22513133

[21] http://www.bmjopen.bmj.com/content/3/10/e003219.full

[22] http://mpkb.org/home/food/vitamind/vitamin_d_supplementation_policy

[23] http://www.toxicologyinternational.com/article.asp?issn=0971-6580;year=2008;volume=15;issue=2;spage=143;epage=144;aulast=Kaur

[24] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1578554/

[25] http://www.news-medical.net/health/Ketogenic-Diet-Side-Effects.aspx

[26] http://link.springer.com/article/10.1385/BTER:83:3:207#

 


 

Future Science - Accurate Diagnosis of Autism Phenotype using Brain Biopsies grown from Skin Cells

 

This is a post for the scientists among you, that like to separate science from pseudoscience.

You may not be aware that in recent years some revolutionary science has been developed allowing you to create a brain biopsy from a sample of skin.  I was rather taken aback when I first read about it, but it is true.  Researchers are now creating their own artificial biopsies, on which to experiment.

I first read about this in work being done at Stanford, looking at Timothy Syndrome.  I did not really focus on the importance of what they had done.  Without physical samples, it almost impossible to develop medical therapies and you cannot take brain biopsies from living people.  Rats and other lab animals are never going to be an adequate substitute.   

Here is a link to Johns Hopkins, where there used the same technology to make a brain sample with Huntington’s disease.

Turning Skin Cells Into Brain Cells

The true potential of this technology is amazing.  Today, it is being used to create samples, with which researchers can carry out experiments.  In future, it could be used as a diagnostic tool, just like when somebody goes to the gastroenterologist and has an endoscopy.  The doctor takes a sample from your intestines and sends it to the lab for analysis; hopefully a few days later you get a call saying the sample had no cancerous biomarkers, or other nasties.

In the case of autism, the skin sample would be turned into stem cells and then neurons from specific parts of the brain could be made.  These samples would then be tested to reveal specific dysfunctions.  This is exactly what was done at Stanford to make samples of Timothy Syndrome, a rare condition nearly always comorbid with autism.

Stanford Research

“We developed a way of taking skin cells from humans with Timothy syndrome and converting them into stem cells, then converting those stem cells into neurons,” says Ricardo Dolmetsch.

He then identified an experimental drug that could reverse the effects.  This phenotype can be reversed by treatment with roscovitine, a cyclin-dependent kinase inhibitor and atypical L-type-channel blocker.

Roscovitine, also known as Seliciclib or CYC202, is an experimental cancer drug produced by a Scottish/American company called Cyclacel. Don’t expect it to be a cheap drug; Goldman Sachs is one of the main shareholders.

Ricardo is from Cali in Colombia and so I had better shift him to my Dean’s List post-haste.

Conclusion

At some, not so distant point in time, people with a lot of money will be able to identify the precise phenotype of their child’s ASD and then they will know exactly what the optimal treatment is.

Once this technology becomes established, maybe in 50 years, I think Psychiatrists will become an endangered species.  We will need a lot of neurologists and for many people with mental health problems, there will at last be the chance of a very precise diagnosis and a matching drug therapy, created and tested on “human” brain samples made from stem cells.

Hopefully by then, the American Psychiatric Association’s DSM nonsense will be relegated to the trash can (or dustbin, for British readers).  Patients with brain disorders will be diagnosed and treated by neurologists and supported by psychotherapists, psychologists, behavioural analysts and other professionals.

 

 

 

 

Autism Phenotypes

Hardly a week goes by without somebody mentioning to me a wonder treatment or even “cure” for autism; the latest one being the GAPS diet.

I think all such reports are worthy of investigation, but many lead to nowhere.

Why is this?




  

·       Medical science has failed to adequately define autism, so we are not all talking about the same autism

·        Many people putting forward theories have not read even the most basic (and not contested) autism research.  Some are even, apparently, qualified “doctors”.
 

Autism Phenotypes

What is not disputed is that autism has many sub-types (phenotypes). Researchers tell us 10-20% of cases referred to as autism have a known genetic defect (Fragile X, SLOS, Timothy syndrome etc.).  80% do not have a known genetic marker/cause.

Autism can be subdivided into regressive (when a child loses speech and other learnt skills) and non-regressive (early onset).  Even this can be a subjective judgment, since it effectively relies on parents to determine it, after the event.

Then you have cases of autism which clearly have nothing to do with Kanner’s classic version.  In this blog I showed how even cerebral malaria in a child can lead to the onset of autism.  This clearly is a case of brain damage caused by malaria; but to the observer, months later, it would probably be classed as regressive autism or childhood disintegrative disorder.

 

Testing for Autism

Researchers and doctors keep repeating that there is no test for autism.  This is not strictly true, but it does explain why so many different conditions are all lumped together as “autism”.

In fact, if you read the research closely, you will see that there are many tests for autism; although they may not be perfect.

The only way to know for sure that it is genuine autism is to examine the brain itself.  The only way to do this 100% accurately is via post-mortem analysis of the brain.  Recently, non-invasive methods have been developed to confirm the same findings of brain malformation that occurred prior to birth.

So the kind of autism that relates to tissue held in brain banks is best understood.  But what kind of autism would that be?  Well, it refers mainly to children and young adults who died prematurely.  They died from things like seizures or drowning.  What does that tell us?  This tells us that these people were most likely severely affected by autism.  The mild, social difficulties, type of autism is, fortunately, hardly likely to make it to the brain tissue bank.

If the person interpreting the MRI of a child’s brain knows what to look for, they may very well be able to identify this type of autism.  The expert here is Eric Courchesne.

A similar approach can followed using Electroencephalography (EEG) to identify autism; but it would be smart to cross check this with Eric.

Regressive vs. Early-Onset

Then you have the difference between regressive and non-regressive autism.  Here again, from my Dean’s List of researchers, we look at Paul Ashwood’s research to see that kids with regressive autism have HIGHER levels of inflammatory markers in their blood.  These include cytokines like interleukin 6, which can be inexpensively measured in most laboratories.  This tells us that perhaps regressive autism is an entirely different condition from non-regressive/early onset autism.  As I would expect, increasing cytokine levels were associated with more impaired communication and aberrant behaviors. 

Elevated plasma cytokines in autism spectrum disorders provide evidenceof immune dysfunction and are associated with impaired behavioral outcome

 

Lab Testing

We have seen earlier in this blog that some very expensive lab tests exist for autism, but their usefulness and integrity is highly disputed.  There are, of course, many hundreds of other tests that are entirely validated by medical science.  Many of these tests are cheap and available all over the world.

Hormonal Screening

We know from the research that about 30% of people with autism have high blood serotonin. A standard lab test is required.

We know that many have high levels of insulin-like growth factor (IGF-1).  A standard lab test is required.

Thyroid hormone levels and in particular a blunted response of TSH to TRH (i.e. central hypothyroidism) can help define further phenotypes.

The TRH test is now not widely used, but TSH, FT3 and FT4 are cheap tests.

Growth Hormone (GH) is also implicated in autism, along with IGF-1; there is a lab test to measure pituitaryfunction to see how well GH is being produced.

By screening for hormonal dysfunction, it would be possible to identify phenotypes that would most likely benefit from therapies targeting those defects, like NNZ-25266.

Pancreatic Dysfunction

It is reported by Joan Fallon, of Curemark, that 50+% of kids diagnosed with “US autism” seem to have a pancreatic dysfunction.  This can be tested for by measuring fecal chymotrypsin level.  The test measures how well your pancreas is working, and is a standard test for people with cystic fibrosis.  Since the US diagnoses far more kids with autism than other countries, it seems highly plausible that “US autism” includes many more phenotypes than, say, “French autism”.

I was quoted about $8 for a chymotrypsin test.

Ion-Channel Diseases (Channelopathies)

Many diseases like Parkinson’s disease, Spinocerebellar Ataxia and Timothy Syndrome are caused by faulty calcium ion-channels.

The Bumetanide autism therapy, undergoing trials in Europe, is based on another channelopathy, this time a faulty chloride transporter NKCC1.

It is clear from reports I have received, that Bumetanide therapy is totally ineffective in some children with ASD, but in other children, like my son, it is effective.

So some types of autism have certain channelopathies and other types have different ones or, quite possibly, none at all.  

Conclusion

My conclusion today is pure conjecture.  I imagine that possibly as few as a quarter of cases of “US autism” are actually “real” autism, that is with all the brain damage/malformation that is identified in those post mortem brain studies and which forms the basis of 90% of autism research.

The other three quarters may be something entirely different, just like the case of the mosquito that bit the child, produced cerebral malaria and then later the full symptoms of autism.  Within the three quarters may be food allergies, digestive enzyme deficiencies, gut disorders, mastocytosis, blood brain barrier defects, undefined calcium ion-channel diseases etc.

This would account for those occasional amazing “recoveries” and the apparent success, in some cases, of diets like GAPS.  Sadly, diet is unlikely to 100% fix brain damage.  If you are lucky enough to totally “recover”, you cannot have had brain damage in the first place.  It is evident that in some phenotypes of autism, diet can reduce autistic behaviours.  This can only be proved in trials, if biomarkers are established for that specific phenotype.

Most likely the only biological thing all these “autisms” have in common is oxidative stress and neuroinflammation; but only a non-medical scientist, like me, can say such a thing.