Showing posts with label Hyper. Show all posts
Showing posts with label Hyper. Show all posts

Monday 7 December 2015

One of Thousands Autism

Some occasional visitors of this blog ask why if one drug helps their case of autism, another can be ineffective.

Perhaps it would be much more helpful right at the start to diagnose people with “one of thousands autism”, then people might better understand their situation,  and plan their way forward.

Autism is not a biological diagnosis, it is just an observational diagnosis.

Some readers have suggested “sorry, we don’t know” would be the honest diagnosis.

Several hundred autism genes and still counting

Some of these 740 genes linked to autism are shown here:-

There are existing mouse models covering 192 individual genes that can cause “autism”.

There are 18 known individual chemicals that can induce ‘autism” in mice

You may wonder how come there is a thimerosal-induced mouse model, but it exists.

There are dozens of rescue models, where scientists can make a mouse have “autism” and then reverse it.

Autism as an Adaptive Response

Any combination of what will likely become at least a thousand genetic and environmental factors can lead to what gets termed “autism”.  Autism is just the result of the brain’s adaptive response to those factors.

Certainly there are common pathways and downstream nexuses, where unrelated dysfunctions converge.

So in the end there will be a manageable number of clusters where most people’s autism can be located.

The thousand autisms will not require a thousand different therapies.

Sooner or later it will be necessary to stop calling it autism and start diagnosing each person’s biological dysfunction.  Only then can you treat it properly.

The efforts of the late Lorna Wing (autism as a “spectrum disorder”, ASD) and Barons Cohen (autism is not a disorder, it’s a friendly “autistic spectrum condition”, ASC) have certainly served to dramatically widen the number of people diagnosed, and even now wanting to be diagnosed, but have made actually treating it, very much harder.

We should start with what Knut Wittkowski, from the previous post, called Strict Definition Autism.  Apply what doctors call triage, start with those where you can make the biggest impact;  minimize cognitive dysfunction (mental retardation), self-injury, aggression and epilepsy.

Your one in thousands Autism

If you took a representative sample of 2015 diagnosed children with “autism”, who would it contain?

The following is based on what appears in previous posts and is not supposed to be definitive.

·        The largest category is probably misdiagnosed autism 

This would include people who are naturally late at developing speech, some people better diagnosed as ADHD, some people with Mental Retardation / Intellectual Disability, people who were deaf during key developmental periods and even people brought up in a cold, stimulus free environment like a 1980/90s orphanage in Romania.  Recall Leo Kanner's refrigerator mother ideas.

Quasi-autistic patterns following severe early global privation. English and Romanian Adoptees (ERA)Study Team.

·        Metabolic disorders that are likely not caused by a single gene

The big one here is mitochondrial disease, often triggered by some environmental event, like oxidative stress or an inflammatory response.  This includes the group that had a viral infection and then regress into autism, usually before the age of five.

There are other metabolic disorders like, cerebral folate deficiency, that are substantially reversible.

·        Then comes the large number of single gene dysfunctions that lead to symptoms that often include autistic behaviors

These vary from reversible to treatable.  Some well-known and not so well known, examples are:-

·        Smith–Lemli–Opitz syndrome (also SLOS, or 7-dehydrocholesterol reductase deficiency) which is in effect low cholesterol

·        Biotinidase deficiency

·        X-linked creatine deficiency

·        Pitt Hopkins

·        Rett Syndrome

·        Fragile X

All the above can be identified by genetic testing, but often are not.

·        Then comes “Dysmaturational Syndrome” which is Tourette’s Syndrome with autism “recovery” by 6 years old

This group accounted for about 5% of diagnoses in a large Italian study.   They do maintain their tics, but the autism features just fade away.

Now we are heading to what the “experts” call “Idiopathic autism”, which is the “we really don’t know”, catch-all category.

This group I will split into hypo/hyperactive pro-growth signaling pathways, based on the clever recent suggestion of Subramanian et al, from Johns Hopkins, we saw in an earlier post.

·        Hyperactive pro-growth signaling pathways

This group includes the textbook classic autism, with accelerated (brain) growth.  They can be identified by some of the following:-

·        Noticeably big head (and brain), maybe just at birth and maybe even Chiari 1 brain hernia (caused by no space for the growing brain)

·        High birth weight and muscular tone as a one year year old

·        Subsequent large drop down the percentiles on growth charts.

·        Hypoactive pro-growth signaling pathways

This group is smaller than the Hyperactive pro-growth category, but is sufficiently large to make most autism clinical trial pretty useless.

In many ways this hypo group are the entire opposite the hyper group, and what is good for them, may well be the opposite of what is good for the others.

This group will have small brains and I presume will have low birth weight. 

This does not mean they will be small as adults.

The hypo/hyper active growth refers to what is happening as the fetus develops and in the first year or two after birth. 

Implications for Clinical Trials and Therapies

It really is not good enough to carry out clinical trials on people, based solely on a DSM behavioral diagnosis of autism.  They are almost doomed to fail and indeed they almost always have failed.

Identify sub-types of autism, based on biological markers and then make trials on one sub-type vs another sub-type.  Then we might actually learn much more.

Some interventions that work in one sub-group should actually aggravate the autism of other sub-groups.  This should be entirely expected.

Autism researchers need to wake up, read other people's research and properly plan their trials based on the entirety of what we already know.  It is not rocket science; that is actually far more complex.  Planning trips to Mars is far more complex than what most autism researchers get up to. 

If you are going to compare therapies with other autism Mums/Moms and Dads, first check that your sub-type of autism is vaguely similar to their sub-type.  Otherwise you may be wasting your time/money and possibly doing more harm than good.


After receiving a diagnosis of autism, ASD or PDD-NOS, I suggest you ask the specialist to be more specific and help find you a biological diagnosis, rather than the observational/behavioral one.

If they cannot give you, at least pointers towards, a biological diagnosis, perhaps they should not be diagnosing  autism? Or just admit “I do not read the autism literature and so I know little more than you; but I get well paid as an autism expert, regardless”.