Mitochondria and autism:time to recalibrate

6 Jun

We all have heard a lot about mitochondria and autism in the past few months.    This message has been dominated for the most part by David Kirby.  Someone got some of the confidential court documents to him, and he leaked one to the public, and discussed another in a news story. 

So, it seems like we are stuck with the idea that “there are a lot more Hannah Polings out there” and “20% of autistics might have mitochondrial disorders” and “1 in 50” (or some such number) “are at risk.” Since the Polings aren’t releasing their information, the government isn’t releasing it’s information, the reasearchers can’t talk and haven’t submitted their paper yet,  we are sort of stuck.  There just isn’t any other specific information out there on people with mitochondria issues and autism.

Is this really the case?

As it turns out, no, this is not the case.  There are a number of descriptions of people with mitochondrial disorders and autism.   And, guess what, they present a different story than we have been fed so far.

We all know about the case study on Hannah Poling.    But, in terms of how many kids (and, presumably, adults) have mitochondrial disorders come from Dr. Oliveira’s group in Portugal.  People tend to use the estimate for autism+mitochondrial disorders from his work (about 4%), but they don’t look closely enough to see that he actually describes a few details on 11 individuals.  In addition,  Dr. DiMauro’s group discussed five individuals in their paper. Gargus of UCI discussed three brothers as well.  Most recently,  Tsao and Mendell discussed two individuals in this paper.

Total it up, and we have information on 22 individuals to consider when we ask the question, “what does autism look like in mitochondrial energy challenged individuals”?

Another way to put it, does mitochondria+autism=Hannah Poling?  Did they all undergo regression ?  Of those that regress, did they all appear normal before regression?   I want to know, because this is what we are being told: autism with mitochondrial disorders/dysfunction result in kids who look normal and then regress.

We get this from David Kirby, who makes statements like:

“That would mean some 190,000 Americans with mito issues who, after normal births and development, suddenly stopped talking and regressed into autism following some kind of childhood fever.”

He seems to be getting this from statements in Hannah Poling’s Rule 4c reports and discussions with the researcher who made them.  Statements (from the Rule 4c report) that describe Hannah Poling as having:

“an etiologically unexplained metabolic disorder that appear[ed] to be a common cause of developmental regression.” He continued to note that children with biochemical profiles similar to [Hannah Poling] develop normally until sometime between the first and second year of life when their metabolic pattern becomes apparent, at which time they developmentally regress.”

David Kirby also uses comments from the researcher stating that he is working on a study of 30 kids similar to Hannah Poling who all underwent regression.  In that as yet submitted study, only Hannah Poling is considered a definite case of vaccine injury.  There is another child whose regression did occur within 7 days of a vaccination.  Somehow, this “possible” case of vaccine injury morphs into a “definite” in the later sections of David Kirby’s blog piece.   I also find it odd that David Kirby claims that people are already preparing to challenge the idea that only 2 of the 30 are possibles.  This, even before the paper is submitted!

Given all the qeustions that are raised, I’d like to know more about what kids with mitochondrial disorders and autism look like.  Don’t you?

The Kids

Let’s first take a look at the DiMauro group paper.  DiMauro’s group discusses 5 kids.  Of those patient 5 had a fever at 14months and showed regression. “At 14 months of age, she had a viral illness with high fever, encephalopathy, regression of previous acquired skills, and significant acidosis. She gradually recovered and continued developing slowly.” Sound like Hannah Poling?  Consider however that she showed developmental delay by 6 months (along with a number of other problems). She did not appear “normal” as Hannah Poling is described before her regression.  Another big difference: Patient 5 had clear mitochondrial disorder.  She has 70% mtDNA depletion in a biopsy sample.  While she is described as “gradually recovered”, she never spoke and is significantly challenged in many areas.

And that is the closest example we get to Hannah Poling in these studies

Patient 3 in the DiMauro study is described as having “…neurologic deterioration during intercurrent illnesses and recovered gradually over several weeks.”  However, he doesn’t fit the “Hannah Poling” mold as he had clear impariments since early infancy.  

The other three patients in the DiMauro study did not have any mention of regression.   There is an Aspie, a PDD kid and a kid with excellent visual/spacial skills but delayed speech and language.

OK, so the DiMauro study doesn’t have “Hannah Polings”.  What about Oliveira?  He describes 11 kids with possible, probable or definite mitochondrial resperatory chain (MRC) disorder.   Of these 11, only 1 is noted as having an “autistic regression”.  (No, it is not noted if this was coincident with vaccination).

One interesting fact in the Oliveira paper: they were studying older kids.  All the kids (with mitochondrial disorder or not) were in the 11-14 year old ages.  Why do I find this interesting?  Because I read a lot of people postulate on the web that Hannah Poling no longer shows “biomarkers” for mitochondrial dysfunction and, thus, thet disappear with age.   People are trying to say, essentially, “A lot of older kids were probably ‘Hannah Polings’ but their tests won’t show mito dysfunction because they are too old” as in, “they were vaccine injured even though we have no proof.”   Since these same people tend to rely on Oliveira’s data to estimate the prevalence of mitochondrial disorders in autism, it seems a bit of a stretch.

In our search for more “Hannah Polings”, we seem to be striking out.  But, there are still two more papers to consider.

Tsao and Mandell describe two patients.  Both were globally delayed from “the early months of life”.  Neither child developed expressive or receptive language, and one never sat up or walked.  Again, these were not “apparantly normal” kids who went through regressions.

Gargus and Imtiaz describe three children, all siblings, who have “a weak mitochondrial defect and a recognized 15q inverted duplication” (we’ll discuss some genetics in another post). The older had poor eye contact and echolalia from early infancy. He developed stimming behavior at age 3 and, sadly, died after a one-day illness at age 5.

OK, sidetrack here.  The authors describe this as  “At age 5, after a 1-day illness, he died suddenly with respiratory arrest and shock, characteristic lethal presentation of a carnitine-deficient fatty acid oxidation”.  In other words, illness can be fatal to the energy challenged.  This is precisely why doctors recommend vaccinating people with mitochondrial disorders, or at least, their close family members.

Back to the paper, the younger twin bothers (monozygotic, monochorionic) hit their developmental milestones in their first year. However, they showed language delay and limited eye contact. One had a near-SIDS event at 4 months, and was the more “severely affected” of the two.

So, the kids in the Gargus study aren’t “Hannah Polings” either as they didn’t regress and showed signs of being “not normal” from early in life.  Now, I suspect people will latch on to the “near SIDS event” at 4 months and suggest that is connected to 4 month vaccines.  No mention of vaccination is made in the paper.

Discussion

There is a huge variation in the presentations of the individuals in the above studies, leaving one to ask, “what can we take away from all of this?”.   One answer is that the huge variation is precisely one of the take-away points: if you think that autism is a spectrum disorder, you shouldn’t be surprised that the mitochondrial energy challenged present as broad or broader of a spectrum.

Second, everyone keeps looking to mitochondria+autism=”must be regressive”.  It just isn’t so.  The “30 child paper” will apparantly concentrate on regressive kids, but the other papers already published do not.

The majority of the individuals described in the DiMauro, Oliveira, Gargus, and Tsao papers show no regression. Of those who do regress, they were not “developing normally” before the regression.

The Bottom Line

The bottom line: Hannah Poling does not appear to be a good representative of the kids with mitochondria issues and autism.   The individuals discussed in papers other than the Hannah Poling case study are very different from her.  Even the other kids in the paper that will concentrate on regressive autism are mostly not like her in one major aspect: they didn’t suffer vaccine injury.

Does that mean that we can’t and shouldn’t learn from Hannah Poling?  Absolutely not.  But, we need to have experts look at and understand all the kids with mitochondrial disorders and autism.  We need this to be a scientific investigation to arrive at real answers, not a series of public relations events to shape the public view.

14 Responses to “Mitochondria and autism:time to recalibrate”

  1. Kev June 6, 2008 at 20:12 #

    Nice one Sully. There’s so much more to this whole situation than is immediately apparent. It reminds me a lot of the early days of the MMR debacle – no science, scaremongering and bad assumptions.

  2. Joseph June 6, 2008 at 21:27 #

    There is another child whose regression did occur within 7 days of a vaccination.

    I would note that in a group of 30 children, let’s say they each are vaccinated twice in a given year, it would mean that one vaccination event in the group occurs every 6 days, in average (that same year). It’s not surprising that 1 or 2 children in the group would have regressions recorded within 7 days of vaccination.

  3. Ms. Clark June 6, 2008 at 21:35 #

    I’m not sure if the oft repeated information about Hannah Poling is accurate or detailed enough for us to know what “a Hannah Poling” looks like. Is Hannah Poling really even a case like the Kirby, Poling and Shoemaker version of “Hannah Poling”. How sickly and how developmentally different was she before she had the big problem with what looked like a chickenpox vaccine reaction? And as I remember mom says Hannah changed practically over night into an autistic child, while dad says it was like turning down a dimmer switch and the change took place over months. So which is it?

    There are too many contradictions in their story for me to just take their word for anything about it, and the parents seem to be unwilling to let the pertinent parts of her medical records speak for themselves.

  4. M Luján June 6, 2008 at 21:35 #

    Hi Sullivan
    You are talking about mitochondrial disorders.

    Please consider this partial evidence at mitochondrial dysfunction in autism
    : J Autism Dev Disord. 2004 Dec;34(6):615-23. Links
    Relative carnitine deficiency in autism.
    Filipek PA, Juranek J, Nguyen MT, Cummings C, Gargus JJ.
    Department of Pediatrics, College of Medicine, University of California, Irvine, CA, USA. filipek@uci.edu

    A random retrospective chart review was conducted to document serum carnitine levels on 100 children with autism. Concurrently drawn serum pyruvate, lactate, ammonia, and alanine levels were also available in many of these children. Values of free and total carnitine (p < 0.001), and pyruvate (p = 0.006) were significantly reduced while ammonia and alanine levels were considerably elevated (p < 0.001) in our autistic subjects. The relative carnitine deficiency in these patients, accompanied by slight elevations in lactate and significant elevations in alanine and ammonia levels, is suggestive of mild mitochondrial dysfunction. It is hypothesized that a mitochondrial defect may be the origin of the carnitine deficiency in these autistic children.

  5. Sullivan June 6, 2008 at 21:51 #

    Maria,

    the Gargus in the Filipek article is the same Gargus as in the post above.

    More to the point, the JADD article does not discuss the behaviors or history of the patients in the study, so we can’t use them to compare here.

  6. María Luján June 7, 2008 at 00:32 #

    Hi Sullivan
    I was not trying to compare the children in both studies; I was trying to present the point that there are biochemical findings that can not be explained by genetic mechanisms of known disorders in ASD. I wonder
    a- MAy be the biochemical findings in ammonia, lactate, alanine and carnitine correlated to some not known nuclear DNA mutation? or
    b-May be them adquired?
    From what I read Hannah Poling seems not comparable to classic mitochondrial disorders, with the known mtDNA mutations.
    In the report of Dr DiMAuro-for example- the 4 children with autistic spectrum disorders were associated with the A3243G mutation in the mtDNA tRNALeu(UUR) gene. Hannah Poling has a point mutation in other section of the mtDNA, the same as her mother, no heteroplasmy, why is she going to be similar if these children are so different between them, even when they carry the same mtDNA mutation?.
    “Dr. Shoffner performed genetic testing on both Hannah’s muscle and her mother’s leukocytes subsequent to our case report. Hannah (muscle mtDNA) and her mother (leukocyte mtDNA) were both found to be HOMOPLASMIC for the mtDNA T2387C transition mutation.
    Our analysis of this genetic finding in the mtDNA was significantly different than those of other physicians that I’ve seen in scientific blogs or commentary. I suspect it would have been fatal to both Hannah and her mother if this homoplasmic mutation was pathogenic since (as I am sure you are aware) the mutation is on the 16S ribosomal subunit which is highly conserved. Thus, this mutation probably represents a benign polymorphism rather than pathogenic mutation” Dr Jon Poling
    There is an interesting review on the topic of Mitochondrial Disorders in Children from Dr Koenig M.K. in Pediatric Neurology May 38(5):305-13 .

  7. S.L. June 7, 2008 at 08:03 #

    Kev,

    Great post. You know me & my interest on this topic. Very good questions asked here.

    I will tell you, of all the mito kids I know (those with and without autism), none had completely “normal development.” Some had only minor delays or health issues (which worsened with age for the most part), others had severe delays or health problems from birth or prior to 12 mos of age. I think there will be children who have regressions–but it will be interesting to see if there were any markers (as in delays or health disorders) prior to regression, and also regressions in relation to vaccines vs. regressions in relation to illness/fevers vs. regressions in relation to X (or even spontaneous).

    Every mito kid I know, when seriously ill (some with the common cold), suffers some type of regression. Sometimes very mild, i.e. the child is unable to speak very well while sick or cannot eat, and recovers immediately after illness. Others, regression can be very significant (of course, this is also dependent upon they type of illness and treatment) and may not regain skills. Our child (once suspected of mito) still has major issues when sick, she appears to “lose skills” (unable to take liquids, less speech, is much weaker, risk of seizures, etc.).

    I’ve yet to meet a parent who has a child with diagnosed mito who is anti-vaccine. Quite the opposite, they are petrified of diseases and of their child getting ill. Very sadly, sometimes it can only take a very “mild” (for the rest of us) sickness that can be fatal to someone with mito.

    Thanks again, this is a great piece.

  8. S.L. June 7, 2008 at 08:19 #

    Joseph & Ms. Clark:
    You each make great points.

    One more point: I think it’s been clearly explained that it’s not surprising to find mitochondrial dysfunction in autistics (likewise, it’s found in people with various diseases, after exercise, in aging…nearly all of us have some form of it–or will). The distinction between mito dysfunction vs. what mitochondrial disease must be understood before anyone make conclusions about there being SO many other “Hannahs.”

    You will find mito dysfunction in autistics (probably a very high %, if not all), but you will not find that same % of autistics with mito disease. In autism, the brain functions differently, so you will find altered mito function. It also helps explain the autistic people with hypotonia, even possibly seizures, feeding difficulties, GI problems, and so on.

    Additionally, this could be why some slight improvements *may* be seen following a DAN protocol. However, I would never give my child any supplement under that protocol, UNLESS the doctor (neurologist) were in fact treating my child for their mito dysfunction (not for, say, vaccine injury etc.). During our mito evaluation period, the geneticist placed our daughter on L-Carnitine. For the first 1-2 mos, we did see (what appeared) to be some improvement in strength. But, that affect seemed to fade as time went on. Having a negative mito result, the docs said it was our choice to keep her on or take her off. We were no longer seeing improvement, we saw no reason to continue the medicine (it also tended to give her diarrhea).

    It is one thing to give your child prescribed (we had an Rx for the L-Carnitine, which we picked up at our pharmacy–not some mail-order warehouse) medicine or supplement, in order to treat a specific mito deficit/dysfunction. It is another to use supplements in an attempt to “reverse” so-called “vaccine injury” or “high levels of mercury,” etc. If you have an autistic child and are concerned about mito dysfunction, speak to your pediatrician, have them run a metabolic profile.

  9. Kev June 7, 2008 at 08:24 #

    Sullivan wrote this one 🙂

  10. S.L. June 7, 2008 at 08:27 #

    Oops…I should have known, much better spelling than you, Kev (JUST KIDDING!).

    Thank you, Sullivan!! 🙂

  11. Kev June 7, 2008 at 08:29 #

    wahteva doo yew m34n 😉

  12. Sullivan June 8, 2008 at 05:33 #

    Hannah Poling has a point mutation in other section of the mtDNA, the same as her mother, no heteroplasmy, why is she going to be similar if these children are so different between them, even when they carry the same mtDNA mutation?.

    this is some of what I am planning on for the next post. A big question here is, how can we be certain that Hannah Poling has no heteroplasmy? The answer, I believe, is we can’t. Heteroplasmy (for the rest of the readers) is where the mitochondria DNA are different in an individual. The thing is, they can be different in a tissue or from tissue to tissue. So, if they did a skeletal muscle biopsy and didn’t see heteroplasmy, are we sure that in other tissues–say the brain–they would find the same?

  13. María Luján June 8, 2008 at 19:14 #

    This link
    points to the discussion of the care and problems with mtDNA confirmation (explained in the link)

    When a new mutation is found in the mt DNA of a patient with a mitochondrial defect, it is important not to assume pathogenecity until a firm link between the mutation and the cellular dysfunction has been stablished…the mt DNA evolves at a relatively high rate containing many polymorphic sites. Several criteria must be met in the criteria of pathogenecity-

    The criteria are
    -Presence of heteroplasmy
    -Clinical /Biochemical correlations and Family history
    -Single Cell PCR
    -Cytoplasmic Hibrid (Cybrid ) constructions.

  14. lacshmiybarra June 10, 2008 at 02:10 #

    Ms. DIva,

    You do not appear to understand the difference between acute encephalopathy and chronic encephalopathy. They are NOT mutually exclusive my dear.

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