Wednesday, November 21, 2012

A Genetic Epidemic of Down Syndrome?

Over at Left Brian Right Brian, Sullivan (aka Matt Carey) is attempting to make an argument that there can be a genetic epidemic.  He says -
It’s a phrase that is heard a great deal in online discussions about autism: there are no genetic epidemics. Genes don’t change quickly enough for a genetic condition to see an increased prevalence over a single generation, right? Well, yes and no.
Before going on to suggest Down Syndrome might be a model for how a genetic epidemic might work.  But while it is true that Down Syndrome is caused by an underlying genetic mutation and that the number of people with Downs is increasing, it does not classify as a "genetic epidemic".

The main reason is that for the most part1 Down Syndrome is not an inherited condition.  A child does not have Downs because their parents passed along any sort of mutation.  Downs is caused by a mistake in cell division during the development of the egg, sperm, or embryo.  So while there is a genetic mutation responsible for the condition, the mutation is caused by some non-genetic factor.

Down syndrome (again, for the most part) doesn't run in families.  Having one child with Downs only slightly increases your chance of having a second child with Downs.

And a person with Downs in unlikely to pass the condition along to another generation because most people with Downs have problems with fertility.  Men with Downs are thought to be sterile and women are only fertile about a third of the time.  Although, if a person with Downs has a child, there is a significant chance that their child will inherit their condition.

So while Downs might be caused by genetic mutations (aka is "genetic"), it is not a "genetic epidemic" because the increasing number of people with Downs is not due to the mutations becoming more common in the gene pool.  What is causing the increasing number of people with Downs is due to a few social changes.

First, there is an ongoing trend for women to have children later in life and maternal age is a demonstrated risk factor for Downs (although, as a side note, I have never read a good explanation as to why exactly that is the case).  The risk of having a child with Downs increases with age, going from 1 in 1,600 when a mother is twenty to 1 in 1,000 at thirty and 1 in 90 by forty.

Second, people with Downs are surviving longer.  Down syndrome comes with a variety of related health problems and these problems can shorten a persons life.  About eighty years ago, people with Downs often didn't survive past their tenth birthday.  Over time that age has gradually increased so that today people with Downs can expect to live to 50 and beyond.

Finally, people today seem to be more willing to have a child with Downs.  Abortions of children with Downs is a contentious subject, but as life expectancy and quality of life for a person with Downs has been improving, there seem to be fewer abortions.

These three factors can explain the modest increase in the number of people with Downs that has been seen over the past several decades.

So, back to Sullivan's original argument, there is no "genetic epidemic" of Down Syndrome.  There isn't really even an "epidemic" of Down Syndrome - the growth has been modest and is what would be expected given the social trends listed above.

More importantly, there aren't that many similarities between Downs and autism -

In autism, there is no single mutation that can account for more than a small fraction of cases and yet having one child with autism does significantly increase the risks of having another child with autism.  Down Syndrome centers on a mutation on one chromosome while autism has been tentatively linked to many places across our genes.  So, from the little we know about the genetics of autism, the underlying genetics of autism and Down Syndrome are quite different.

Autism does not automatically come with medical conditions that shorten life expectancy.  And there is no prenatal test for autism2 and so there are no widespread abortion trend that is reversing.

Autism is growing much, much faster than Down Syndrome.  Over a twenty four year period (1979 to 2003), the number of people born with Down Syndrome grew by 31.1%.  Over the same time period, the number of case of autism grew from about 2-4 per 10,000 to 66 per 10,000 or about 1500%3.  If you take a more conservative time period (2000 to 2008), autism has grown about 160%.  Anyway you slice it, autism is growing significantly faster than Downs.

The only real link between Downs and autism is parental age, and that is a nebulous one at best.  Some studies of autism involving parental age show a small relationship with maternal age but not paternal age, some show a relationship with paternal age and not maternal, some show a relationship with both, and some show no relationship to either.

At the present time, the best that we can say is that there might be some relationship between maternal or paternal age and risk of autism.  Compare that to Down Syndrome where there is a clear link between maternal age and the risk of having a child with Downs.

So, not only is Sullivan wrong to suggest that there is a "genetic epidemic" of Downs Syndrome, he is wrong to suggest that there is any epidemic of Downs at all or that this tells us anything about what is going on with autism.

1. There are actually three different known types or styles of genetic mutations that can cause Down Syndrome. The most common one, trisomy 21, accounts for more than 90 percent of cases and is almost never inherited.  Another form, which is almost not normally inherited, involves a mutation of chromosome 21 where only some of the cells have the mutation and others don't.  The final form, called translocation Down Syndrome, can be passed from carrier parents to children.  However, only about 4% of Downs cases are these type and only about half of these cases involve inheritance.  Source

2. Well, technically, there are prenatal tests for some known genetic forms of autism, such as Rett Syndrome and Fragile X.

3. A large part of the growth in autism from the 1980 to 2000 is probably due to the condition being added t the DSM III and then its changes in the DSM IV.

Saturday, November 17, 2012

Diabetes More Common in US

In health news that is not related to autism, the CDC has published a report that the prevalence of diabetes in the United States has risen sharply over the past fifteen years.  This report estimates that 8.2% of the adult population suffers from diabetes in 2010, up from 4.5% percent in 1995.

Yes, you read that figure correctly - roughly 1 out of every 12 adults in the US now has diabetes.

The CDC gives a few possible reasons for the increase -
  1. Improved survival of people with diabetes.  Deaths among US adults with diabetes declined substantially over the same time period.
  2. An actual increase in the number of cases.  
  3. Changes in diagnostic criteria, demographics, and lifestyle.
  4. Enhanced detection.
The report also notes that  the increase of diabetes coincides with the increase in obesity across the United States, although it does not draw any firm conclusions from the association.

And just to drive the point home, here is a chart of how the prevalence of diabetes has changes over the past 15 years.  I think the trend is rather clear, don't you?

Thursday, November 15, 2012

Study : Fecundity of People With Mental Disorders

According to a recent study, people who have schizophrenia, autism, and anorexia nervosa have fewer children than the general population.  This isn't a particularly happy topic or one that I enjoy dwelling on, but it is a rather important topic to think about when trying to understand whether autism is becoming more common.

One the one hand you have the idea that autism is strongly genetic and runs in families but on the other you have the inconvenient fact that having autism greatly reduces your chances of having children.  You would think that those ideas aren't compatible, that the families who have a higher than normal number of members with autism would not keep going generation after generation as they would be "strongly selected against".

Of course the issue isn't really that simple as that.  There are many other factors involved that might be contributing to these families staying around such as extremely mild symptoms of autism, recessive traits, the relative rarity of autism, and the like that could explain both facts.

But still, even if both ideas are true and autism is strongly genetic and "strongly selected against", you would, at best, expect it to stay about the same prevalence.  It would look more like schizophrenia which is "genetic" (and environmental), runs in families, and is "strongly selected against" and still manages to stay at a relatively constant 1% of the population.

Yet with autism we have three ideas that really can't go together - that autism is strongly genetic, that autism makes you a lot less likely to have children, and that the number of cases of autism is growing fairly rapidly.  Although to be fair, all three of these statements are gross oversimplifications of the complex realities of autism.

Just food for thought.  The abstract of the study is below.

Fecundity of Patients With Schizophrenia, Autism, Bipolar Disorder, Depression, Anorexia Nervosa, or Substance Abuse vs Their Unaffected Siblings

Context  It is unknown how genetic variants conferring liability to psychiatric disorders survive in the population despite strong negative selection. However, this is key to understanding their etiology and designing studies to identify risk variants.

Objectives  To examine the reproductive fitness of patients with schizophrenia and other psychiatric disorders vs their unaffected siblings and to evaluate the level of selection on causal genetic variants.

Design  We measured the fecundity of patients with schizophrenia, autism, bipolar disorder, depression, anorexia nervosa, or substance abuse and their unaffected siblings compared with the general population.

Setting  Population databases in Sweden, including the Multi-Generation Register and the Swedish Hospital Discharge Register.

Participants  In total, 2.3 million individuals among the 1950 to 1970 birth cohort in Sweden.

Main Outcome Measures  Fertility ratio (FR), reflecting the mean number of children compared with that of the general population, accounting for age, sex, family size, and affected status.

Results  Except for women with depression, affected patients had significantly fewer children (FR range for those with psychiatric disorder, 0.23-0.93; P < 10-10). This reduction was consistently greater among men than women, suggesting that male fitness was particularly sensitive. Although sisters of patients with schizophrenia and bipolar disorder had increased fecundity (FR range, 1.02-1.03; P < .01), this was too small on its own to counterbalance the reduced fitness of affected patients. Brothers of patients with schizophrenia and autism showed reduced fecundity (FR range, 0.94-0.97; P < .001). Siblings of patients with depression and substance abuse had significantly increased fecundity (FR range, 1.01-1.05; P < 10-10). In the case of depression, this more than compensated for the lower fecundity of affected individuals.

Conclusions  Our results suggest that strong selection exists against schizophrenia, autism, and anorexia nervosa and that these variants may be maintained by new mutations or an as-yet unknown mechanism. Bipolar disorder did not seem to be under strong negative selection. Vulnerability to depression, and perhaps substance abuse, may be preserved by balancing selection, suggesting the involvement of common genetic variants in ways that depend on other genes and on environment.

Power RA, Kyaga S, Uher R, Maccabe JH, Långström N, Landen M, McGuffin P, Lewis CM, Lichtenstein P, Svensson AC. Fecundity of Patients With Schizophrenia,  Autism, Bipolar Disorder, Depression, Anorexia Nervosa, or Substance Abuse vs Their Unaffected Siblings. Arch Gen Psychiatry. 2012 Nov 12:1-8. doi: 10.1001/jamapsychiatry.2013.268. [Epub ahead of print] PubMed PMID: 23147713

Wednesday, October 31, 2012

What's Wrong With Diagnosing Yourself with Autism?

Self-diagnosis is the process of identifying a medical condition in oneself.  You look at signs and symptoms that you have and try to match them to a medical condition.  This process is prone to error under the best circumstances and potentially dangerous under worse ones.

In the autism community, there are some number of adults who have self-diagnosed themselves with a form autism.  They may refer to it using other phrasing, such as ASAN's "self-identif[ied] with the Autistic community", but it is really the same thing.  These people have looked at themselves and decided that, based on their behaviors, they have some form of autism.

The people will typically say that the self-diagnosis was a wonderful thing for them or how it changed their life.  And while, at first glance, it might seem like there is nothing wrong with this practice, it has been my experience that self-diagnosis is almost never a good thing for anyone involved.

In my opinion, if a person thinks that there is something wrong with them, they should not try and guess what it is themselves.  They should instead go talk with an unbiased professional who will be able be able to help them.  This is true for strictly physical problems and is doubly true for profound mental problems such as autism.

There are many reasons for this as a general statement, but here are some specific ones for autism.

1. Everybody has strengths and weaknesses.  Everybody has things that they are good at and other things that they struggle with - this is "normal" and expected.  So just because you have problems or struggle in some areas does not mean that you have a mental disorder.  Mental disorders are defined by their extreme behaviors - behaviors that are so far out of the realm of what is typically seen that they cause problems.

Autism is (currently) defined by profound impairments in three areas - communication, socialization, and repetitive/restricted interests and activities - that must appear in early childhood and that must act together to impair every day life.

For example, the ability to focus on a subject and become extremely knowledgeable is well within what is considered "normal".  You don't have autism (or a "trait" of autism) simply because you find a subject very interesting and can spend a lot of time learning about it.  It is only when the ability to focus turns into a constant fixation or obsession that you go from what is "normal" to something that isn't.

So, to be perfectly blunt, just because you are don't relate well to others and have some strong interests does not mean you have autism.  Along the same lines, just because a person is a "geek" or in some other technical profession doesn't mean that they are automatically on the spectrum somewhere.

It means that you have areas that you need to work on and improve in, just like everybody else.

2. It is hard enough for a "typical" person to objectively and accurately analyze and understand their own behaviors.  If you do actually have a mental disorder then that means that your ability to understand and objectively analyze your own behaviors will likely be impaired.  This is true not just in autism but most of the other major mental disorders such as ADD, schizophrenia, depression, and addiction, to name just a few.

To put that another way, if you are relying on your own opinions and observations about your behaviors and you do actually have a disorder then you will most likely be getting it wrong.

3. There are very few "objective" measures of autism and all of the reliable ones require a trained professional.  But there are some rather crappy ones that are promoted online by various that will likely give you the wrong idea.

Probably the most well know and most abused of these is the Autism Quotient.  The AQ is a meant to be used as a screening test in an appropriate setting with appropriate supports in place.  It is not meant as a test to see if you have autism.  Even if you get an extremely high score that will only raise your chances of having autism to like 1 in 10.  And the AQ cannot tell the difference between autism and other conditions such as schizophrenia.

I cannot count the number of times I have run across people who have decided that they have autism based on their own observations of their behaviors and their score on the AQ.  Some of these people might well have a form of autism but the numbers suggest that most would not.

4. Even if you do have some profound problems in the three core areas of autism, that does not mean that you have autism.  There are several other conditions, such as ADD,  schizophrenia and OCD, that overlap with autism and it can be difficult to tell them apart.  You have to consider the complete picture of all of the behaviors that a person has, when those behaviors appeared, as well as what behaviors are missing to be able to tell them apart.

This is why an objective, unbiased professional is critical to the process.  They should know not only what the different conditions look like and what the signs of each are but also how to tell them apart.  They will know the little things like an AQ isn't a diagnosis and that a high score could mean schizophrenia or autism.

Accurately determining what (if any) condition you have is absolutely critical for the next point.

5. You have to make sure that any treatments are appropriate for your condition.  If you taken it upon yourself to decide that you have a condition then you may use treatments that are completely inappropriate for your actual condition.  More importantly, if you have decided on the wrong condition, you could miss out on treatments that could really make a difference in your life.

If you have decided that you have a form of autism but also decided that you don't need any form of treatment, then I would ask why you think you have a disorder in the first place.  The point of a medical label is to identify a condition so that you know what you are dealing with and how to treat it.  A medical label is not an identity.

(And no, "the rest of the world needs to just accept who I am" is not a treatment.  Not that acceptance itself is bad or unneeded, but it will rarely be enough to give you back the ability to function in the world.  More on this in a bit.)

6. You have to ask yourself what a self-diagnosis of autism will actually do for you.  While at first glance it might seem like the label can help you make sense of your life, it really can't.  The autism label might provide a plausible sounding rationale for your behaviors but the label alone doesn't necessarily help you deal with or improve those behaviors.  For that you need an objective person who will be able to consider all aspects of the behaviors and help you arrive at an appropriate strategy.

And if you are just looking to use the label of autism as an ongoing justification for your actions and are refusing to change yourself in any way (i.e. you are in the "autism is just a difference camp"), then I have two little words for you - grow up.  You are supposed to change and adapt your behaviors in response to your environment, even when you would rather not and it is uncomfortable to do so.  Autism is not an excuse for behaving badly.

Just to be perfectly clear here, if you are disabled by a mental disorder then you are entitled to the same rights that everybody else is.  You are not less of a person simply because you have a disability.  You have the right to expect that others will still treat you as an equal and you have the right to expect that  accommodations will be made to help you function better.

But if you have the ability to change and improve yourself but choose not to because you think that you are defined by a medical label then you really do have a problem.  And the problem isn't that you have autism.

Which leads to the last and very unfortunate problem.

7. There are certainly many people in the world who do have autism, who struggle because of it, and who are able to speak about it publicly.  These people provide an invaluable service because they enable the rest of us to better understand what it is like to have autism.  I applaud their courage to speak out about their condition and am extremely grateful for the insight they provide.

But then there are a number of people who have self-diagnosed with autism and then rush to tell the word "what it is like" to have autism.  These people often spread inaccurate information about what autism is and what effects it can have on a person.  These people cause direct and lasting harm to people who actually do struggle with autism by giving a false impression of what autism is and by drawing attention away from people who are actually disabled by their autism and truly do need the help.

These people often encourage other people to self-diagnosis or "look into it" for themselves.  They are often the people who use autism as a justification for their actions and claim that it is the rest of the world who have a problem and not them.  These people certainly do have issues but, in my opinion, that problem is rarely autism.

So, for these reasons and quite a few others, if you think you have a serious mental disorder such as autism, please don't try and diagnose yourself.  Instead go get the help you need.  There is no shame is trying to get help when you need it and you have everything to lose and very little to gain from diagnosing yourself.

P.S. The practice of diagnosis shopping, i.e. going to multiple professionals until you find one that agrees with your self-diagnosis, is almost as bad as diagnosing yourself in the first place.  There is certainly a time when a second (or third or fourth) opinion is certainly a good idea but there is a clear difference between trying to find a professional who can help and going to multiple professional until you find one that agrees with you.

Monday, October 22, 2012

Temple Grandin: Autism Is Not My Identity

Temple Grandin on autism as an identity -

I am a scientist and college professor first and a person with autism second. Autism is an important part of me, and I do not want to change, but my career is my identity, not autism.
I get concerned when young kids come up to me and all they want to talk about is “their autism.” I would rather talk about their interest in animals, science, or history. They are becoming their label.

Go read the full article, there are many good points in it.

Saturday, October 20, 2012

The Sum of All Genetics

A interesting paper was published a few days back on the genetics of autism that suggested that the genetic component of autism is made up of not one or two large mutations but rather many small mutations that add together to increase risk.

As the paper put it -
For simplex families, who have only a single affected individual in multiple generations, approximately 40% of liability traces to additive effects whereas this narrow-sense heritability exceeds 60% for ASD individuals from multiplex families.
Or to put that another way, you can only blame genetic mutations for roughly half the risk of autism.  This idea isn't necessarily new but it is the first time that I have seen it presented so openly in a paper with the names of so many prominent autism researchers attached.

I'm not going to dig into the methods used in the paper because, quite frankly, I have no real understanding of the methods used to arrive at the result and so I don't have an opinion on whether the results fit the data.  If you want a good summary of the results in the paper, I suggest you read the write up over at Questioning Answers.

What I am going to point out is the excellent background section at the start of the paper.  The paper is open access, so I if you are interested in the genetic of autism I suggest you read at least that section.  I also wanted to point out two little bits from this section -
Beliefs about the genetic architecture of autism spectrum disorders (ASD) have changed dramatically over the past few decades. Early twin studies produced heritability estimates approaching 90% and, while no specific risk loci were known at the time, it was believed that liability was conferred by a handful of genes of large effect. Later, data on the distribution of ASD within families, together with results from linkage analyses, were interpreted to mean that liability arose from many genes. Recent work has definitively demonstrated the substantial contribution of de novo variation. Indeed multiple studies of rare single nucleotide and copy number variants (CNVs) have suggested that 15% or more of liability traces to de novo mutation, effects that are genetic but not inherited.
[D]espite a near-consensus that common and transmitted variation must confer liability, multiple genome-wide association studies have so far not revealed replicable common polymorphisms associated with ASD, and studies of rare structural and sequence mutations have largely failed to account for the anticipated risk associated with transmitted variation.
I may be reading too much into these statements, but it almost seems like the paper is admitting that the assumption that autism is primarily an inherited genetic disorder is flawed.  Of course, the data in the paper tries to save the idea by suggesting that the genetic risk for autism comes from tens, hundreds, or thousands of small inherited mutations which, when acting together, give a greater risk for autism.

And who knows, that idea may actually be true.  Maybe the genetic side of autism does in fact come from many small mutations acting together.  But here is the thing about science - it is all about the evidence.  An estimate from applying some fancy algorithm to an already over analyzed genetic data set doesn't tell us anything new.

Despite a "near-consensus" that there have to be common genetic mutations that are passed from parent to child that increase the risk of autism, the fact is that after years upon years of looking no one has found them.  All that has been found are some relatively rare inherited conditions and a bunch of non-inherited mutations that, when taken together, make up the minority of cases of autism.

In fact, I would say that the lack of findings despite the efforts to date make a pretty convincing case that such common mutations do not exist, the evidence of twin and other studies notwithstanding.  Maybe it is time to start looking in more promising areas such as epigenetics or the biology of autism?


Klei L, Sanders SJ, Murtha MT, Hus V, Lowe JK, Willsey AJ, Moreno-De-Luca D, Yu TW, Fombonne E, Geschwind D, Grice DE, Ledbetter DH, Lord C, Mane SM, Lese Martin C, Martin DM, Morrow EM, Walsh CA, Melhem NM, Chaste P, Sutcliffe JS, State MW, Cook EH Jr, Roeder K, Devlin B. Common genetic variants, acting additively, are a major source of risk for autism. Mol Autism. 2012 Oct 15;3(1):9. [Epub ahead of print] PubMed PMID: 23067556 DOI : 10.1186/2040-2392-3-9

Thursday, October 18, 2012

Genetics, Twins, and Autism

I think I may have mentioned this once or twice in the past but, at the risk of repeating myself, let me say it again.  I am somewhat skeptical about the idea that autism is a primarily genetic disorder consisting of hundreds of extremely rare mutations.

I understand the evidence that suggests that autism is "genetic".  I understand that twin studies suggest that something about being a twin greatly increases the risk of autism and that the risks are greater for identical than fraternal twins.  But what I don't understand is why the presumption is that genetics is the cause of the greater risk.  I don't understand why the other things that twins have in common - such as a shared prenatal and early childhood environments - are often ignored or overlooked.

For example, the existing evidence suggests that a fraternal twin has a greater risk of autism if their twin has autism than other, non-twin siblings do.  Fraternal twins are no closer genetically than other other siblings so the increased risk over non-twin siblings has to come from shared environmental factors.

And then there is the little fact that the genetics of even identical twins isn't as straight forward as you might think.  Yes identical twins start off with identical genetic material at the moment of conception, but after that point things can get a little murky.

As I think I have mentioned in the past, my identical twin daughters who both have autism each have their own set distinct set of mutations.  Under the standard assumption that identical twins are always genetically identical that shouldn't happen.  But clearly someone forgot to tell them that they shouldn't be like that.

 Just because identical twins start out with the same genetic code when they split from each other a few days after conception doesn't mean they will still be identical when they are born.  But if my little anecdote doesn't make you say hmm, then consider the following abstract of a study that was just published -

Monozygotic twins discordant for submicroscopic chromosomal anomalies in 2p25.3 region detected by array CGH.
Although discordant phenotypes in monozygotic twins with developmental disorder are not an exception, underlying genetic discordance is rarely reported. Here, we report on the clinical and cytogenetic details of 4-year-old female monozygotic twins with discordant phenotypes. Twin 1 exhibited global developmental delay, overweight and hyperactivity. Twin 2 had an autistic spectrum disorder. Molecular karyotyping in twin 1 identified a 2p25.3 deletion, further confirmed by FISH analysis on leukocytes. Interestingly, array-CGH was normal in twin 2 but FISH analysis using the same probe as twin 1 showed mosaicism with 1/3 of cells with a 2p25.3 deletion, 1/3 of cells with a 2p25.3 duplication, and 1/3 of normal cells. Genotyping with microsatellite markers confirmed the monozygosity of the twins. We propose that the chromosome imbalance may be due to a mitotic non-allelic recombination occurring during blastomeric divisions of a normal zygote. Such event will result in three distinct cell populations, whose proportion in each embryo formed after separation from the zygote may differ, leading to discordant chromosomal anomalies between twins. We also discuss that the MYTL1L and the SNTG2 genes within the reported region could probably relate to the phenotypic discordance of the monozygotic twins.
Makes perfect sense, right?

OK, the text is a little bit dense, so lets break it down a little bit.  In this study there is a pair of four year old identical twin girls who have different but related developmental disorders -

Twin 1 -
  • has global developmental delay (intellectual disability)
  • is overweight
  • is hyperactive
  • has a deletion at 2.25p3
Twin 2 -
  • has autism
  • did not have an overall mutation at 2.25p3
  • but did show signs of mosaicism, meaning that roughly -
    • 1/3 of her cells had a 2.25p3 deletion
    • 1/3 of her cells had a 2.25p3 duplication
    • 1/3 of her cells had a normal 2.25p3 gene
If that last bit about one twin having a deletion at 2p25.3 while the other has a partial deletion and a partial duplication of the same gene leaves you confused, you aren't alone.  I had to read the abstract a few times and look up what some of the terms meant before it started making sense to me.

I haven't read the full text of the study but there are a few things that jumped out at me.

First, genetics - even in the case of identical twins - is not simple.  Most people hear the word "identical" and jump to the conclusion that identical means exactly the same.  But as this abstract and other results have shown, identical twins aren't exactly the same.  You cannot assume that because one twin has a certain genetic mutation that her twin will have the same.

Second, just because you can point to developmental differences between identical twins and can find a mutation in one twin does not mean that the mutation is automatically the cause.  There has to be a mechanism related to the mutation that could cause the differences.

Third, when you find differences in the genetics of identical twins, the fact that there are differences might be more important than what the actual differences are.  Any mutation that is not shared has to happen after conception but before the fetus gets large enough that a mutation wouldn't be able to spread to the entire body.

Since these mutations cannot be inherited there has to be something in the prenatal environment that causes them (and please don't say random chance).  It seems, at least to me, that any factor that is strong enough to cause permanent genetic change would also be able to play havoc with the delicate developmental process of the fetus.

Finally, you have to look at the overall picture of the twins to see if the mutation is important.  In the study the twins both have different yet related developmental disorders - global developmental delay and autism.  Since these conditions are so closely related and since it can be difficult to tell the difference between the two (especially in four year olds), I think the fact that both twins are both developmentally delayed is more important than the subtle differences between the two.

The bottom line here is that presumption that autism is largely genetic rests heavily on twin studies but the genetics of twins isn't as straight forward as you would think.  When you add in the facts that there isn't an "autism gene" or even a small set of "autism genes" but rather hundreds of mutations that might each account for a very small number of cases and that even identical twins don't always share these rare yet presumed causal mutations, the genetic presumption starts to look a little weak.


Rio M, Royer G, Gobin S, de Blois M, Ozilou C, Bernheim A, Nizon M, Munnich A, Bonnefont JP, Romana S, Vekemans M, Malan CT. Monozygotic twins discordant for submicroscopic chromosomal anomalies in 2p25.3 region detected by array CGH. Clin Genet. 2012 Oct 15. doi: 10.1111/cge.12036. [Epub ahead of print] PubMed PMID: 23061379.

Thursday, October 11, 2012

State of Pennsylvania Backs Down on Autism Income Tax

On Friday of last week, the State of Pennsylvania backed away from from implementing its controversial autism copayment requirement for Medical Assistance.  In a released statement, Department of Public Welfare Secretary Gary D. Alexander said -
Oh shit, that didn't go over well.
Ahem, seriously, what he said was -
The department has always preferred the option of applying a premium to this program and will be working with stakeholders who have come to us in support of a premium as opposed to the co-payment.  Therefore, we have decided to delay the co-payment initiative, and families will not owe a co-payment for any services until further notice.

Stakeholders have clearly indicated to the department an understanding of the need for families to contribute to this program. With the delay, there is an opportunity to work with stakeholders to continue to pursue the premium from the federal Centers for Medicare and Medicaid Services. We look forward to working with them in achieving this shared goal.

Once a decision is reached, we will immediately inform any affected families.
Even though there is a bunch of nonsense in there about "stakeholders" begging asking to pay a premium instead of a copayment, the message is clear.  The copayment that would have caused economic hardship and potentially a loss of services for many families in Pennsylvania whose children have autism was stopped in its tracks, at least for now.

If you are living outside of the State of Pennsylvania or aren't a part of the informal parental networks in the state, you might wonder why the proposed copayments only lasted for about two short weeks before being yanked.

The answer is simple - the measure was stopped dead by the combined voices of thousands of families across the state.  Once the parents, families, and professionals who would have been impacted by the copayment became of aware of what was going on they mobilized and attacked the issue head on.  There was a march on the capital, a bill introduced in the PA House, calls to elected officials, and organized meetings about how to tackle the problems.

I think once the State of Pennsylvania figured out how seriously the autism community was taking this issue they decided it wasn't worth the fight.  It probably didn't hurt that elections are literally right around the corner either.

Sunday, September 30, 2012

State of Pennsylvania Imposes 5% Autism Income Tax

Families who have children with autism and live in the state of Pennsylvania have had a pretty good deal for a while now.  That's because Pennsylvania is one of the few states that has provided free medical coverage called Medical Assistance (MA) to children with severe disabilities, such as autism, regardless of parental income.  The really nice thing about MA is that it not only covered normal medical expenses but also paid for evidence-based autism specific treatments such as speech therapy, occupational therapy, and (most importantly) ABA.

The MA program isn't perfect by any means.  It involves a lot of paper work, a lot of red tape, and the only real way to navigate the system is by talking to families that have been in the system longer.  And when it comes to the autism specific therapies, another related group gets involved in managing your child's treatment down to having to approve each goal and method on your child's treatment plan.  So it isn't like MA is some sort of all you can eat buffet - each and every autism specific treatment has to be medically necessary, completely supported by the available evidence, and you have to be a strong advocate for your child's needs.

Then, each and every year, you have to reapply for  the benefits and most years you have to provide a new medical evaluation proving that your child still has autism.  Even though managed care side requires periodic evaluations and treatment plans and is almost involved in the day to day treatment of your child.  So once a year you have to spend several weeks trying to get a hold of the person assigned to your case (who changes constantly and is virtually impossible to get a hold of) and making sure that they have all of the paper work they need, haven't misplaced anything, and will process it all before the date when the services will be cut.

Or, in other words, the MA program is exactly like most other bureaucratic government run programs. But by and large the system generally works.  It can be a little bit of a pain to navigate, but once you learn what you need to do it works decently well.  After dotting each i and crossing each t, jumping through multiple hoops, and standing on your head while rubbing your stomach, you can access some rather decent services for your child and the only cost is your sanity.

Seriously, I don't have any major complaints with the system besides the bureaucracy and I am extremely grateful that it exists.  We would not have been able to afford even a fraction of the life-changing therapy that my children have received over the years without this system.  And just to be perfectly clear here, we have good private health insurance that covers a lot of my children's medical needs and I make a decent living.  So it isn't like we simply lack the means to provide these therapies but rather that these therapies are so expensive (40k+ per year per child) that even fairly well off families have no chance.

But now, in an effort to save a couple of bucks, the State of Pennsylvania has decided to impose a copayment on certain services provided by MA to families that earn more than 200% of the federal poverty level.  This copayment will be up to 20% of the cost of the services and capped at 5% of a families gross monthly income.  Since the base price of autism specific services is so expensive, all but the wealthiest families are going to hit that 5% cap.

At first glance this copayment might seem perfectly fair.  After all, no one really has the right to expect certain services from the government and most families whose children have autism receive far more benefits from the state than they pay in taxes.  But in reality what this copayment is going to do is mean that many children with autism are going to lose services because many families are not going to be able to afford the copayments.

Lets consider a few examples.

A single mother who has one child with autism will be hit with the copayment if she makes more than 30,260 per year.  At that level of income, she would be expected to pay about 1,500 per year in copayments or about 120 per month.  A family of five that earns more than 54,020 would be expected to pay 2,700 per year or about 225 per month.

I don't think I need to explain to other autism families about the financial burden that having a child with autism can cause.  Even if basic medical costs and the core autism specific treatments are covered (as is currently the case in PA), there are still very substantial out of pocket expenses that directly relate to autism each and every month.

And that doesn't even begin to take into account the financial opportunities that are lost to autism.  There are many families where one of the parents has to forgo working to take care of the children and there are many parents who are unable to take advantage of professional opportunities because of the limits that autism imposes.

I don't want to sound like I am complaining but this is reality of having children with autism.  I wouldn't trade my children for anything (except maybe versions of them that could talk and slept at night) but providing appropriate treatments and supports is very expensive to begin with.

So when the State of Pennsylvania comes in and tells me that they want 5% of my annual gross income because that's my "fair share", I just have to laugh.  My family, like most other autism families that I know, is already spending more than we can afford in an effort to give our children the best possible future.

No, what this new copayment is is basically a new income tax on families that can't really afford it.  To put this new tax into perspective, the existing state income tax stands at 3.07%.  This new income tax is going to more than double the effective state income tax, raising it to 8.07%.

If this new charge was really meant to be a copayment rather than a new tax then, it should work like other copayments work.  If any other insurance company came in and charged a premium for the plan and then, when asked about copayments, said  "it depends,  how much do you make" then they would likely loose most of their customers.

Lets not forget that the purpose of health insurance is to spread the cost around to everyone that participates in the insurance pool.  Everybody pays a premium, everybody has the same copayments, and the pooled premiums are used to pay for the health expenses.  Some people will have very few expenses and will pay in premiums than they get back in coverage and some people will have extreme expenses and will get far more back than they put in.

As a tax payer, I already pay my premiums on both the state and federal level (the MA program receives money from the federal government) in the form of income tax.  I am not against copayments as long as the amounts are reasonable and applied fairly.  But the way that this copayment is being implemented (more on that in a bit) makes it clear that it is a targeted charge on a very narrow group of people.

Of course the counter argument here is that I always have a choice and don't have to pay the copayment.  I could choose to not have the services for my children, I could choose to go with less expensive services, or I could choose to go with a different type of health insurance.

But all of these options are just illusionary and there is no real choice.

As a parent, I would be negligent if I did not do everything in my power to provide medically necessary services for my children.  As a consumer, I have extremely little ability to change the cost of services or to pick less costly services.  When you have to spend your time fighting to get any services let alone appropriate services, you have no ability to haggle over the price.  And as for a choice of health insurance, there is no choice.  The choice is between no services or Medical Assistance.

So basically the "choice" comes down to not having medically appropriate services for my children or paying an extra 5% of my gross income to the state every year.

The end result here is going to be one of two things.  Either a family will be able to afford this extra tax and continue services for their children or they will be forced to cut services for their children.  My family may be able to cut enough other things that we will be able afford this new tax and continue services but I suspect that many other families won't be able to do so.

I am sure that the State would disagree with me characterizing this copayment as a new tax.  In fact, they say that "targeting co-payments based on ability to pay will ultimately protect the safety net and allow us to continue to effectively serve Pennsylvanians now and well into the future."

The problem is that the State's own numbers belie their own assertion.

According to the numbers that they provide, providing these disability specific services costs taxpayers "approximately $700 million a year".  But the potential savings from this copayment are approximately $4.3 million per year or about 0.6% of the total spent.

When you put these numbers in terms of the entire yearly MA budget, the result is even more absurd.  The MA program cost $16 billion for fiscal year 2012-13, of which roughly $8 billion was spend on people with disabilities (all disabilities, not just autism).  So terms of the amount spent on all disabled people we are talking about 0.05% of the budget.  In terms of the entire budget we are talking about 0.03%.

I don't see how pushing 0.03% of the total expenditures back onto families will "ultimately" protect the system.  If the goal is to protect the system you might need to start were you actually are spending a noticeable amount of your budget.

But I can see how pushing that amount back onto families who are already financially struggling will result in a loss of services to disabled children.

And then there is the matter of how this copayment was announced (see if you can find it in there), how public comments on the copayment were basically ignored, the extremely short time period between announcing the copayments and them taking effect (about a month), and the fact that other ways that the State could better offset the costs that are already active.  For example, PA Act 62 requires certain private insurance to pay up to 36,000 per child per year for ABA services.  If that act were actually implemented and fully enforced that could save the State over $30 million a year.

There is also the little matter of implementation.  This copayment is supposed to become active on Monday, October 1st (yes, tomorrow)  for new families and a month later on Nov 1st for existing families but there is almost no information a family can use to figure out how much of a copayment that they will be hit with.  Under the new system, each provider will be responsible for independently collecting the copayment for their services and there is some magical and yet to be determined method for coordinating charges across providers to make sure that a family isn't overcharged.

My children have services spread out across three or four providers and I have absolutely no information about how they bill for services, how much of a copayment will be charged for each service, nor is there any system in place for me to question the charges.  So when (not if, when) I receive bills that total more than the 5% of our monthly income, do I pay the bills and try and get the money returned in the future or do I try to dispute the charge and constantly risk service disruptions and my credit rating?

In theory I could contact the state department that is responsible for the program but since they can't even get their phone system working well enough for me to be able to reach them via phone and the chance of an email or regular letter being answered  is about a million to one, I am not going to hold my breath.

And even when you do get a hold them their idea of customer service is somewhat lacking.  I once had the person assigned to my children's case tell me that she gives priority to children who have "real problems" and since my children just have autism they would just have to wait for her to get around to their case.

In other words, the actual implementation of this new copayment is likely to be a complete and utter mess and it is going to take a substantial amount to keep track of it all.  And that's just want families whose children have autism need, one more large problem to deal with.

Friday, September 14, 2012

Revisiting the Rhetoric About the Pertussis Epidemic

A few years back, I talked quite a bit about how pertussis (aka whooping cough) was becoming more common again and what the reasons for it might be.  Back then, the reason du jour in the mainstream media and certain parts of the autism world for the epidemic was that the more and more parents were refusing to give their children the pertussis vaccine which was leading to a decrease in herd immunity and allowing pertussis to make a come back.  This was the reason used in spite of the fact that there was evidence, even back then, that other factors played a larger role in the pertussis epidemic.

Well, lets fast forward to today and a study1 that was just published in the New England Journal of Medicine that suggests that the main cause of the pertussis epidemic is that the vaccine induced immunity doesn't last nearly as long as was previously thought.

The old idea was that the vaccine induced immunity gradually faded over the years so that a person who was fully vaccinated would only need a booster shot every 8-10 years or so to maintain their immunity.

The new idea is that the vaccine induced immunity starts fading quickly after the last vaccine dose.  According to the study, the odds of contracting pertussis increased an average of 42% per year.  So instead of needing a booster in ten years to maintain immunity, this finding suggests that the immunity is almost gone ten years out.

But that ten year figure assumes that the vaccine is at least 97% effective in the first year.  If, as other recent results have suggested2, the vaccine is much less effective than previously though, the immunity would fade even faster.  If the vaccine were 90% effective to start that would mean the protection would be cut in half in about four years and largely gone in six years.

These numbers are just approximations and are going to vary based on a large number of factors but I think the overall point is clear - the current pertussis vaccine isn't nearly as long lasting as was previously thought.  The data from the outbreaks going on around the country also supports this idea.  I'm not going to go into details but, as an example, roughly one third of the cases in outbreak in California in 2010 were in mostly vaccinated children from 5 to 7.

So the main reason that pertussis is becoming more common isn't that parents are refusing the vaccine but rather that the vaccine doesn't work as well as it was thought to.  While this reinforces the idea that vaccines play a critical role in protecting the population from serious illnesses it also serves as a reminder that vaccines aren't sacrosanct.  A vaccine should not be assumed to be safe and effective just because it is on the vaccine schedule.

This also serves as a reminder that we should wait for actual data and not jump to conclusions.

If you are interested in further reading on the subject there is the study abstract here and there are articles in Time, Web MDThe Wall Street Journal, ABC News, and CBS News.


1. Klein NP, Bartlett J, Rowhani-Rahbar A, Fireman B, Baxter R. Waning protection after fifth dose of acellular pertussis vaccine in children. N Engl J Med. 2012 Sep 13;367(11):1012-9.
PubMed PMID: 22970945. DOI: 10.1056/NEJMoa1200850

2.Witt MA, Katz PH, Witt DJ. Unexpectedly limited durability of immunity following acellular pertussis vaccination in preadolescents in a North American outbreak. Clin Infect Dis. 2012 Jun;54(12):1730-5. Epub 2012 Mar 15.
PubMed PMID: 22423127 DOI: 10.1093/cid/cis287

Saturday, September 8, 2012

Rare and Potentially Treatable Form of Autism

A group of researchers has identified a possible biological mechanism that might be responsible for a rare form of autism. In these cases, mutations of the BCKDK gene inactivates an enzyme that is necessary for breaking down certain types of amino acids.  These essential amino acids cannot be created by the body and can only be absorbed from food.

It isn't clear exactly how the absence of these essential amino acids leads to autism however there is some limited data from mice and anecdotal data from parents that providing appropriate supplements can restore the normal level of these amino acids and lead to improvements in the symptoms of autism.

If all of that sounds a little confusing, think of it this way.  A small genetic mutation prevents you from absorbing critical substances from your food and the long term lack of these substances causes autism.

If you are interested in more information about the subject, there is a good write up over on Questioning Answers, there is an article in Nature describing the finding, as well as the actual paper.  There is also some details about what the the BCKDK gene does and prior links to autism here and here.

At the risk of sounding like a broken record, I think it is going to become increasingly clear over time that many, if not most, cases of autism are going to caused by a process like this.  We are going to find that there are disruptions to critical biological processes that lead to the symptoms of autism and that by correcting these biological disruptions we will be able to help people recover from autism.

We are going to find that the behaviors of autism are a side effect (co-morbid, if you will) and that the real problem is the biological disruption and the damage that causes.  So instead of the brain being wired "differently" because that it is written into the person's genes, it wired differently because some process is preventing it from developing normally.

However, as I said before, a critical part of a model like this is that recovery will be a two step process.  Simply correcting the underlying disruption will not instantly remove the symptoms of autism.  It will take time for the body to recover from the damaged caused and it will take time for old behaviors to be unlearned and new skills to be learned.

But the important part is that autism can be successfully treated.  The key is going to be finding what the disruptions are in a specific person and finding a way of correcting those disruptions.

Wednesday, September 5, 2012

The End of Junk DNA

In case you were living under a rock today I thought I might point out the major genetic news of the day.  The idea that the majority of our genome (98%) is "junk dna" that does nothing meaningful because it isn't directly involved in creating proteins has been overturned.

According to a gaggle of papers released today (six in Nature alone), it turns out that this "junk" actually plays a very important regulatory role in controlling how and when the non-junk dna does its job. Or, as an article on Nature puts it -
One of the more remarkable findings described in the consortium's 'entrée' paper is that 80% of the genome contains elements linked to biochemical functions, dispatching the widely held view that the human genome is mostly 'junk DNA'. The authors report that the space between genes is filled with enhancers (regulatory DNA elements), promoters (the sites at which DNA's transcription into RNA is initiated) and numerous previously overlooked regions that encode RNA transcripts that are not translated into proteins but might have regulatory roles.
Or, as I would put it, the 2% of our DNA that was thought to be significant is only a small part of the picture.  What matters more is whether that small part is turned on or off and when these transitions happen.  There doesn't have to be a known mutation in a known gene for a part of the biological processes in a person's body to be messed up.  There are many things that can control how genes are turned on or off and today we learned of yet another major one.

There are news articles in all of the major outlets such as the NY Times, The Washington Post, The Wall Street Journal, and Business Week just to name a few.  And there is an excellent resource on the Nature site as well.

Time will tell what this means for people with autism but I predict a renewed interest in "junk" genetic mutations associated with autism.   Which will be a little bit of a shame, really, since the idea that autism is "genetic" has almost been put out to pasture.  First it was mutations are strongly associated with autism, that came up largely empty, then it was copy number variations are strongly associated which was another bust, now it is going to be junk dna causes autism.  I think this avenue of investigation is going to be a bust as well but at least it might get people looking at genetic regulatory mechanisms which is where I suspect the problem actually is.

I guess we will have to wait and see what happens.

Sunday, August 12, 2012

Study : Comparative RNA editing in autistic and neurotypical cerebella.

The topic of this new study is somewhat beyond my level of understanding but it is intriguing.  It seems to suggest that the expression of genes in the brain can be altered by a process that is susceptible to environmental signals and that this process is more active in the brains of some people with autism.

The abstract is below.

Comparative RNA editing in autistic and neurotypical cerebella.

Adenosine-to-inosine (A-to-I) RNA editing is a neurodevelopmentally regulated epigenetic modification shown to modulate complex behavior in animals. Little is known about human A-to-I editing, but it is thought to constitute one of many molecular mechanisms connecting environmental stimuli and behavioral outputs. Thus, comprehensive exploration of A-to-I RNA editing in human brains may shed light on gene-environment interactions underlying complex behavior in health and disease. Synaptic function is a main target of A-to-I editing, which can selectively recode key amino acids in synaptic genes, directly altering synaptic strength and duration in response to environmental signals. Here, we performed a high-resolution survey of synaptic A-to-I RNA editing in a human population, and examined how it varies in autism, a neurodevelopmental disorder in which synaptic abnormalities are a common finding. Using ultra-deep (>1000 × ) sequencing, we quantified the levels of A-to-I editing of 10 synaptic genes in postmortem cerebella from 14 neurotypical and 11 autistic individuals. A high dynamic range of editing levels was detected across individuals and editing sites, from 99.6% to below detection limits. In most sites, the extreme ends of the population editing distributions were individuals with autism. Editing was correlated with isoform usage, clusters of correlated sites were identified, and differential editing patterns examined. Finally, a dysfunctional form of the editing enzyme adenosine deaminase acting on RNA B1 was found more commonly in postmortem cerebella from individuals with autism. These results provide a population-level, high-resolution view of A-to-I RNA editing in human cerebella and suggest that A-to-I editing of synaptic genes may be informative for assessing the epigenetic risk for autism.


Eran A, Li JB, Vatalaro K, McCarthy J, Rahimov F, Collins C, Markianos K, Margulies DM, Brown EN, Calvo SE, Kohane IS, Kunkel LM. Comparative RNA editing in autistic and neurotypical cerebella. Mol Psychiatry. 2012 Aug 7.

doi: 10.1038/mp.2012.118. PubMed PMID: 22869036

Saturday, July 21, 2012

Read Between The Lines

A very interesting study was just released that showed that disruptions of the immune system can lead to the behaviors of autism, at least in mice.  There are quite a few write ups of the actual results, such as herehere, here, or here, so I won't try to add anything to these already good reviews.

Instead I want to go for gross oversimplification of the findings because the pattern it suggests is, in my humble opinion, a good guide to what autism actually is for many people.  Ready?

1. Mother's immune system is given a swift kick.
2. Child's immune system is thrown out of balance.
3. Child develops behaviors of autism later in life.

and, most importantly -

4. Correcting the child's immune system reduces the autistic behaviors.

Of course this is all in mice and doesn't automatically translate into humans.  But given all of the evidence of immune disruptions in autism I strongly suspect that we will see some effective evidence based therapies for autism that target these disruptions within the next ten years.

You can call this pattern anything you want but the key elements are that something is biologically out of balance in people with autism and that correcting the imbalance can lead to "recovery" from autism.

Read that last sentence again because I feel that it is the key to putting together all of the things we know about autism. Instead of the current idea that autism is a fundamental part of who a person is (i.e. it is written into their genetic code), this model suggests that autism is a state that a person's body is in. There is still room for genetic mutations in this model but these mutations are important insofar as they make it easier for a person to get into a disrupted state.

I could write pages and pages about how this model fits into what we know about autism but since I don't have that much time nor I am not under the delusion that anyone would actually want to read that, I will just quickly hit the highlights.

1. The "genetic" model of autism is a bust.  There is no single mutation or group of mutations that occur in any sizable part of the autism population.  The mutations that have been found can be significant for the people who have them but I think they are really just background noise in the larger discussion of what causes autism.

2. The number of people with autism is increasing rapidly.  There are a number of reasons for this increase but it isn't really possible to deny that there has a real and substantial increase in the number of people who have autism.

3. There are many, many, many biological disruptions that are seen in substantial subsets of people with autism.  I always have to laugh when people dismiss these disruptions as unimportant (or "co-morbid") because they only appear in like 30% of people with autism and then turn around and trumpet the latest genetic finding as significant when it appears in maybe 1% of people with autism.

4. There is substantial evidence from other related conditions, such as Retts, Fragile X, SLOS, Wilsons disease, and the group of conditions called inborn errors of creatine metabolism (just to name a few), that correcting the biology corrects the condition even when there are genetic mutations present.

All of these ideas fit nicely into the model of autism as a biological disruption.

You don't have to have some genetic mutation that is "causing" autism, all you need something strong enough to push a person out of equilibrium.  And something that is strong enough to do that could likely cause the random but almost unique mutations that are seen in autism.

The number of people with a specific genetic disorder isn't likely to change rapidly but biologically induced disorders certainly can and do.  If you want a model of that consider Pink's disease.  It came, it rapidly rose, and then, once the cause was found, it disappeared just as quickly as it appeared.

The same can be true for the autism epidemic if get our collective heads out of our asses and stop thinking of autism as some permanent thing and instead consider it as an imbalance that can and should be corrected.

(Before anyone decides to leave a less than polite comment suggesting that I am calling people with autism defective, calling them less than typical people, or wants to suggest that I don't like my children, don't waste your time.  I am not saying, implying, or suggesting anything of the sort.  If you want to interpret my words to mean that then you are certainly entitled to your opinion, but I will ask you to take your stupidity elsewhere.  Serious comments - even if you want to tell me I am completely wrong - are always welcome. )

Thursday, July 5, 2012

Study : Yet Another Immune System Abnormality in Autism

A new study has reported that a large number of children with autism may have an elevated level of interleukin-17A.  This isn't a new result but it is interesting because this time there appears to be an association between the level of IL-17A and the severity of autism - the more severe the case, the higher the level of IL-17A.

If you are interested in the subject I suggest you read the (open access) paper.  It has some good background material about other immune system abnormalities that have been found in autism.

The one thing that I would like to point out is that this elevated level of IL-17A was seen in almost half of even a moderate sized group children with autism - 22 out of 45.  Compare that size and number to what passes for significance on the genetics side of autism research where finding 3 or four children with similar mutations out of a group of thousands is considered significant.

The abstract is below.

Elevated serum levels of interleukin-17A in children with autism.
Al-Ayadhi LY, Mostafa GA.

The T-helper (Th)1/Th2 dichotomy dominated the field of immune regulation until interleukin (IL)-17-expressing T cells (Th17) were proposed to be a third lineage of helper T cells, the key players in the pathogenesis of autoimmune disorders. Autoimmunity to brain tissue may play a pathogenic role in autism. IL-17A is a pro-inflammatory cytokine that has been shown to play an important role in various autoimmune neuroinflammatory diseases. The aim of this study was to measure serum levels of IL-17A in relation to the degree of the severity of autism.

Serum IL-17A levels were measured by ELISA in 45 children with autism and 40 healthy matched healthy controls.

Children with autism had significantly higher serum IL-17A levels than healthy controls (P <0.001), with increased serum levels of IL-17A found in 48.9% of the autism group. Patients with severe autism had significantly higher serum IL-17A levels than those with mild to moderate autism (P = 0.01), and raised serum IL-17A levels were significantly more common in children with severe autism (67.9%) than in those with mild to moderate autism (17.6%), P = 0.001.

Serum IL-17A levels were raised in the group with autism, and the levels correlated significantly with the severity of autism. This is the first study to measure levels of IL-17A in relation to the severity of autism, to our knowledge. Further research, with a larger subject population, is warranted to determine whether the increase of serum IL-17A levels plasma has a pathogenic role in autism, and whether anti- IL-17A therapy could be useful.

Al-Ayadhi LY, Mostafa GA. Elevated serum levels of interleukin-17A in children with autism. J Neuroinflammation. 2012 Jul 2;9(1):158. [Epub ahead of print] PubMed PMID: 22748016.

Friday, June 22, 2012

Smear Blogging

Today must be my lucky day, my last post was the subject of a smear post written by the lord high smear blogger himself, Orac. Or, since he decided to get personal from the start, I think I should just call him by his real name, David Gorski. Gorski apparently didn't like the subject of my last post and decided to write one of his typical rambling rants about it, or as I like to call them, smear posts.

I call them smear posts because the good doctor doesn't like to confine himself to facts and talking about ideas. No, he seems to feel the need to editorialize about and impugn the character of everyone he writes about while impressing us with his brilliance. For example, I apparently don't understand science based medicine.

I was going to respond to his post with one of my own but after reading the comments on the his post I changed my mind.  I actually had to laugh at how inane some of these people are.

One particularly sad person took me to task for not thanking Gorski for plugging my blog and giving me a forum to correct my errors before telling me my "tone" was offensive.  According to this person, I defend child abusers.

Another explained to me that because I was having saying inappropriate things about MMS that I am one of its defenders.  And another one counted the number of words I wrote and decided that I spent too many words saying the wrong about MMS thing therefore I had to be defending it.  That was right before he said that I was "sampling the wares".

You really can't make stuff like this up.  I didn't think that my thoughts on MMS were unclear, but in case anyone didn't get the point, here it is from the top of the other post -
Now, let me be perfectly clear here. I see absolutely no reason to think that using this stuff will do anything to help my children's autism and I see a lot of potential for harm.
I can see why there is all of the confusion, that statement (and others like it) were totally ambiguous.  Or maybe, if you believe the post and the people making comments, I am really secretly an MMS sympathizer and my entire post was just a ruse.  Drat, they figured me out.

Like I said, I was going to respond to Gorski's points but, after reading some of the comments, I realized that it is completely pointless.  There is absolutely no point in engaging with these people because many of them are just fanatics.  Internet blowhards like Gorski exist because they can collect followers who feed into their desire to be important and because people will actually engage them.  If you can't see the huge ego staring out from behind Gorski's writing then you aren't paying attention.

I don't have any need or desire to prove to the world that mine's bigger than everyone else's.  You can take what I say and agree with it, disagree with it, or tell me I am an idiot, it is entirely up to you.  Gorski apparently thinks I'm an idiot and I really couldn't care less.

So, yea, good job David, you really showed me. Although, just between you and me, you really sound like an idiot when you say stuff like paying attention to differences in chemical composition is pedantry and it is the class of chemical that is more important.  Because I can totally see how that option fits into science based medicine.   After all, acetaminophen and ibuprofen are both pain relievers so they are exactly the same thing too, right?

But since I do care about accuracy, I will correct one potential mistake that I made in the last post.  The dose of chlorine dioxide in a single, uhm, serving of MMS might be higher than I thought it was.  I said that I though it was around 1 ppm and I based that on comments that I read around the internet.  According to Gorki, that dose is like 80 ppm and while I think that figure is probably wrong (anyone with a good knowledge of chemistry want to chime in?), I also think my figure is an under estimation.

However, even if you remove that one point, the rest of the post still holds true.  The hyperbolic rhetoric employed by people like Gorski and his ilk might be good for firing up the minions but it does nothing productive for the larger autism community.

Tuesday, June 19, 2012

OMG, Its Bleach! (Updated)

There are some days that the autism community drives me crazy.  It seems like it is impossible for any of the various factions to put aside their ideology and, just for once, communicate clearly and accurately about important issues.

Take for example the latest craze gripping the blogosphere - an autism "treatment" that goes by the name of "Miracle Mineral Solution", or MMS, that has been around for years but recently had a presentation at Autism One.

There were many presentations at Autism One that covered a wide range of subjects.  But which presentation does the remnant of the old neurodiversity movement focus on and hold up as the poster child of the conference?  MMS, of course, and how it is so dreadful that immediate action is needed to stop the horror.

The current coverage of MMS sounds awfully like the rhetoric about HBOT that was being spread by almost the same group of people several years back, so I spent some time looking at all of the current claims about MMS.  If you want to spare yourself some time and effort reading what follows, the best word to summarize the current claims is overblown.  Using MMS is, more likely than not, a bad idea but listening to all of the nonsense being said about it is also a bad idea.

Still here?  Well, don't say I didn't warn you that this was going to be a bit long.

If you haven't heard of MMS until now you are not alone.  I didn't know what it was until the stories about it started popping up all over the place.  According to the little bit of research I did, MMS is supposed to do many wondrous things by killing everything that it comes into contact with, except the things that it shouldn't, by summoning the magical scrubbing bubbles of ClO2.

Ok, that wasn't very clear or accurate, but I got as far as the word "Miracle" in the name and was immediately skeptical.  Miracle cures don't work unless you are Miracle Max.  But, if you seriously want to know the details of what this stuff is supposed to do, I suggest looking at here or at the presentation given at Autism One.

Now, let me be perfectly clear here.  I see absolutely no reason to think that using this stuff will do anything to help my children's autism and I see a lot of potential for harm.

The FDA said as much when they put out a warning about using it.  But, then again the FDA takes a dim view of anything claiming to have medicinal properties that has not gone through its review process, so harsh words from the FDA is not an automatic sign that a product doesn't work.

But I don't want to talk about the fact that MMS likely doesn't do anything helpful, that topic has been covered ad nauseam by many others.  No, what I wanted to talk about are the misleading statements such as  MMS is bleach, MMS is "industrial bleach (which means it's stronger)", and that using it is, as the (cough, cough) Thinking Person's Guide To Autism so nicely put it, "child abuse and tantamount to torture of autistic children".

The core of these claims is that giving MMS to your children is the same as giving them bleach and we all know that giving your child bleach is morally wrong.  And that line is both right, wrong, and completely irrelevant at the same time.

Just to set the ground rules, the standard that ANY treatment should be measured against is how well it works and how much damage it causes while working.  In a perfect world, all treatments would be both perfectly effective as well as perfectly safe.

We do not live in a perfect world.

In our imperfect world world, there are no perfectly effective treatments that have no side effects.  Almost every treatment to have some level of undesirable side effects to go along with any possible benefits.  So the goal of any treatment is to make sure the good that comes from a treatment outweighs the bad.

So for MMS, lets cut to the chase and assume that the stuff doesn't do anything good for you and look at the bad side to see if the harm rises to the level of torture.

The first claim on the harm side is that MMS is bleach.  Now, I don't know about you, but when I think of bleach, this is the stuff that comes to mind -

(Picture of bleach bottle removed) 

MMS is not the same as this stuff.

This stuff is (typically) a mixture of (roughly) 5% sodium hypochlorite while MMS is 28% sodium chlorite.  While the names sound quite similar, they are not the same thing nor do they have the same properties.  The best thing you can say is that they are similar chemicals that do similar things.

But most people aren't going to care (or understand) about the chemical differences between the two.  Most people are going to hear "MMS is bleach", make the automatic association to the stuff in the picture above, and react emotionally based on that.   As Wikipedia puts it "the solution of sodium hypochlorite [...] is so ubiquitous that many people just call it 'bleach'".

That is the first problem with the claims, the choice and usage of the word "bleach" almost seems designed to create confusion.  The structure of many of the references I have seen makes it seem like it is a reference to the stuff in the bottle above because the reference reads like "bleach" is a proper noun.

The say "MMS is bleach" the same way that a person would say "this bottle is bleach".

A better and less confusing way to rewrite the sentence is that MMS is a bleach to indicate that it is a bleach in the technical and more generic sense of the word.  As in (again, Wikipedia), a bleach is "a number of chemicals that remove color, whiten, or disinfect, often via oxidation."

So no, MMS is not bleach in the common use of the word, but you might be able to say that MMS is a bleach.

But then again, if you wanted to get really technical, the claim that MMS is a bleach is still partially wrong.  My chemistry is a little weak but, from what I understand, the sodium chlorite in MMS isn't a bleach by itself but needs to be combined with something else to form the actual bleach.   The same holds true for the stuff in the bottle; it isn't much of a bleach until the chlorine is separated from the sodium by some chemical reaction.

In the case of MMS, the real bleach is chlorine dioxide.  And, as I have learned over the past year of balancing the level of chlorine in a swimming pool and hot tub, not all forms of even chlorine are the same let alone bleaches that are different types.  For example, lithium forms of chlorine are about half as effective as sodium forms, even at the same concentration.

That last bit is kinda important, so it bears repeating.  The strength of a bleaching chemical is determined by the amount and type of bleach that is present in the final mixture, not by the initial concentration.  You can't assume that one form of a bleach (chlorine) is going to be equivalent to another, chemically different form of bleach (chlorine dioxide).  If you do even a little bit of research into the differences between chlorine and chlorine dioxide you would know that they aren't the same thing.

If all of that gets too technical, just go with what the FDA had to say about the process -
The product, when used as directed, produces an industrial bleach that can cause serious harm to health. The product instructs consumers to mix the 28 percent sodium chlorite solution with an acid such as citrus juice. This mixture produces chlorine dioxide, a potent bleach used for stripping textiles and industrial water treatment
Or basically, when used as directed, the end result is that MMS forms a chemical that can remove color, whiten, or disinfect, i.e. a bleach.

The FDA adds in additional "industrial" phrase, and that is true, chlorine dioxide is used in the textile as well as other industries.  But that also ignores the fact that chlorine dioxide is also used in making processed foods, in sanitizing water for human consumption, and (as sodium chlorite) in some personal care products.

Certain people also seem to be misreading the "industrial" word as meaning extremely strong instead of meaning the more literal meaning of used in industry.  Another example of the "industrial" uses of this product is making white flour - in some cases, flour is literally sprayed into the air in a room full of chlorine dioxide to remove the color (and all of the nutrients) from the flour.  If you ever wondered how flour turns white or why it has to be enriched after the fact it is because it was bleached.  So, if you eat white flour, you are possibly eating a food that has been bleached by the same bleach in MMS.

But lets forget about the "industrial" scare and the different types of bleach for a minute and talk about some of the other common uses of bleach.  Have you ever gone in a swimming pool or hot tub?  Then, chances are, you have gone swimming in bleach.  There is no difference between the chlorine in a swimming pool an the chlorine generated by a standard household bottle of bleach.  If you children have ever swallowed any pool water (I know mine do all of the time), they you have basically given your children bleach.

Other common household uses include personal care products such as toothpaste or mouthwash, sanitizing reverse osmosis water filters, and your everyday cleaners.  Do you let you kids eat off of a table after you just used a cleanser on it?  Congratulations, you probably just gave them some bleach.

And then there is the fact that many municipal water supplies (in the US at least) are sanitized using some level type of bleach.  There are detectable levels of bleach or bleach by-products (yes, those sometimes count as bleaches) in normal everyday tap water.

The point is that expose to or ingestion of bleaching chemicals is not some rare or horrific event.  It literally happens every day.  And, if you are really worried about chemical exposures, then you really should be more concerned about antibacterial soap, Bisphenol A, household cleaners, VOCs, and a host of other chemicals that children are being exposure to everyday.

Of course the counter argument here is that MMS is a "purer" form of bleach, and that is partially true.  You may be will be exposed to more of a bleaching chemical when you drink an MMS cocktail than when you shallow some water from an average residential swimming pool.  How much more (or less) depends on exactly how much MMS is used, what exactly it is mixed with, and how fluid much it is diluted in afterwards.

The target number that you are supposed to get to with MMS is 1 ppm (part per million) of chlorine dioxide.  Although since there are so many variables that determine the final amount of the bleaching chemical in the final mixture it would be pretty easy to make a mistake and make it far stronger than it should be.

For reference, residential tap water can contain up to 0.8 ppm of chlorine dioxide and a residential swimming pool typically has about 5 ppm of chlorine.

However, the variable strength of the mixture is one of the two large drawbacks to using MMS.  You should not need a degree in chemistry to be able to safely use an over the counter supplement.  The other drawback is, of course, that it is likely that drinking even a properly mixed MMS cocktail doesn't do anything good for you.

Regardless, assuming that you use the product "correctly", you would be exposed to not much more chlorine dioxide than is allowed in tap water and, on a ppm basis, less than what is in a typical swimming pool.  Again, my chemistry is a little weak, but I don't think that 1 ppm of chlorine dioxide is going to do much harm when tap water contains almost that much and a typical swimming pool contains 5 times that amount of a different type.

So, the idea that giving this mixture to a child is some sort of child abuse or torture is just plain silly.  If that level of exposure is torture, I would hate to see what these people would say about me letting my children spend hours in the pool everyday.

EDITED TO ADD : Ignore the crossed out text above, it is wrong. The bottom line is that even using a single drop of MMS is a standard sized glass is a little over six times stronger than pool water - roughly 32ppm.  And it gets worse the more drops that you use at a time or if you take it multiple times per day.  See this discussion for more details.

But lets side aside the whole "bleach" idea and look at what harm this stuff can do if you take it.  Remember, any treatment should be judged on the benefits it gives and the harm that it does.  Even if we agree that MMS doesn't do anything at beneficial, we can still look at the harm side to see whether it is just another pointless treatment or whether it is truly harmful.

If this idea seems contrived then just think of all of the mainstream treatments that are used every day that can have harmful side effects and yet give no real benefit.

 If you read the lists of potential side effects that are being published everywhere, this stuff sounds almost like straight poison.  But there is a difference between all of the theoretically possible side effects that are included in these lists and the ones that will happen on a regular basis.

So lets put these side effects into perspective.  The following items are "common" side effects from MMS, two drugs, and a supplement.  All of these things are commonly used yet have times that they are used when they might have few, if any, benefits.

See if you can figure out which one is which without peeking at the answers below.

1. Headache, nervousness, drowsiness, dizziness, heartburn, constipation, diarrhea, stomach pain, increased salivation, pain, especially in the arms, legs, or joints.

2. Nausea, vomiting, diarrhea, symptoms of severe dehydration,

3. Fever, nausea, vomiting, diarrhea, metallic taste, kidney and stomach damage.

4. Upset stomach, vomiting, diarrhea.

Figure it out?

The item in question are

1. Aripiprazole - a drug to treat irritability in autism
2. MMS
3. Zinc supplements
4. Amoxicillin, a commonly used antibiotic.

So, the side effects of MMS are very similar to those that can happen when using other common treatments.  Does that mean giving Aripiprazole to your child when it isn't clear that there will be benefits "child abuse"?  Does the medical profession's constant overuse of antibiotics qualify as torture?

Of course you can say that MMS doesn't have any potential benefits to offset the negatives.  You can say that all it does do is rid you of those couple of extra dollars that were floating around in your wallet.  But, in reality, you can't even say that.

There is a tiny little distinction in evidence based medicine that is commonly forgotten but is really important to the whole thing.

There are treatments that have evidence that show that they are effective.  These are the treatments you should, more likely than not, be using.

There are treatments that have evidence that shows that the treatment are not effective.  These are the treatments that, more likely than not, you should not be using.

And then there are the treatments that have no real evidence one way or the other.  You can say that these treatments don't have evidence that they work but you can't say that they have evidence that they don't work.  A lack of data is a lack of data - not evidence against the treatment.

I think it goes without saying but if you want to attempt to use a treatment from that last category, you should  do your homework and exercise extreme caution in doing so.  But, having said that, if you shy away from a possible autism treatment just because it is not completely supported by the evidence, then you don't have many treatment options to work with.

MMS clearly falls into that last category - there is nothing that says it works but there is nothing that says that is doesn't either.  So, if you are going to be one of the, uhm, brave souls to try it, you had best be very careful and be sure you understand exactly what it might do and the harm it could cause before even thinking about it.  And if you can't do the calculations to figure out what amount of sodium chlorite is needed with what type of acid to produce the required ppm of chlorine dioxide in your head then you shouldn't be using it.

In all seriousness, it is pretty likely that MMS doesn't do anything beneficial but it still has some very real side effects.  But, it is not as bad as everybody is making it seem.  MMS may be a type of bleach but it is a far cry from pouring pure, concentrated laundry bleach down a kids throat - which is what everybody seems to be implying.  And using it is certainly not a form of torture or child abuse.

And that is really the point of all of this.

A calm, non-emotional, and objective look at MMS shows that it likely does nothing that we want to do and it has some potentially problematic side-effects.  And that is the standard that should be used to judge ANY treatment for a child with autism - evidence based or not.

The standard should not be who can make the most absurd claims or who can get a nonsensical claim repeated the most.  It is in everybody's best interest to go for clear, accurate information and to forgo the polarizing rhetoric that seems to be far to common in the autism world.  These sorts of claims might be good for getting the troops all lines up and ready to go, but it does very little to actually help anybody.

So, how about we all turn down the rhetoric a little?

EDITED TO ADD: And in case you didn't get the point about MMS from what I already said above, here it is very simply put - don't use it.