Mitochondrial Disorders Common in the General Population, But What About for Autism?
August 12, 2008 by Kristina Chew, PhD
Filed under Health
An article in the July 31st American Journal of Human Genetics suggests that mitochondrial DNA (mtDNA) mutations are “common in the general population.” According to the study, one in 200 people has a DNA mutation that could potentially cause a mitochondrial disease in them or in their offspring. Mitochondrial disease is (according to the United Mitochondrial Disease Foundation (UMDF) ) a “devastating and often fatal disease, and mitochondrial disorders are at the core of many well known diseases and chronic illnesses, such as Alzheimer’s disease, Parkinson’s disease and autism spectrum disorders.” Mitochondria are the body’s main energy source; are in almost all of our body’s cells; and produce “more than 90 percent of the energy needed by the body to sustain life and support growth.” While symptoms and the severity of the disease may vary from person to person, symptoms include “difficulty breathing,” “uncontrollable seizures and/or digestive problems,” and not being able “to walk, talk, see or hear.” Mitochondrial disease has been linked to diabetes, cardiovascular disease, Parkinson Disease, Alzheimer Disease, various cancers, multiple sclerosis and lupus.
And, too, autism: 9-year-old Hannah Poling was the child in the case earlier this year in which the government conceded that vaccines had exacerbated her underlying mitochondrial disorder and led to symptoms of autism. In the wake of this announcement, the question of how common are mitochondrial disorders in autistic children keeps recurring, and also whether or not there is some subpopulation of mitochondrial autism. Dr. Jon Poling, a neurologist and the father of Hannah Poling, has argued that mitochondrial disorders “may not be rare at all among children with autism.”
Here’s the abstract for the study from American Journal of Human Genetics:
Mitochondrial DNA (mtDNA) mutations are a major cause of genetic disease, but their prevalence in the general population is not known. We determined the frequency of ten mitochondrial point mutations in 3168 neonatal-cord-blood samples from sequential live births, analyzing matched maternal-blood samples to estimate the de novo mutation rate. mtDNA mutations were detected in 15 offspring (0.54%, 95% CI = 0.300.89%). Of these live births, 0.00107% (95% CI = 0.000870.0127) harbored a mutation not detected in the mother’s blood, providing an estimate of the de novo mutation rate. The most common mutation was m.3243AG. m.14484TC was only found on sub-branches of mtDNA haplogroup J. In conclusion, at least one in 200 healthy humans harbors a pathogenic mtDNA mutation that potentially causes disease in the offspring of female carriers. The exclusive detection of m.14484TCon haplogroup J implicates the background mtDNA haplotype in mutagenesis. These findings emphasize the importance of developing new approaches to prevent transmission.
Again, mitochondrial disease is linked to a number of diseases, with autism spectrum disorder only one among them. Further, the symptoms of mitochondrial disorder are these, according to the UMDF:
loss of motor control, muscle weakness and pain, gastro-intestinal disorders and swallowing difficulties, poor growth, cardiac disease, liver disease, diabetes, respiratory complications, seizures, visual/hearing problems, lactic acidosis, developmental delays and susceptibility to infection
Aside from “developmental delays” (not further specified), these are not, in and of themselves, symptoms of autism, whose DSM criteria are here. Mitochondrial disease are linked to diseases ranging from Alzheimer’s to Parkinson’s to diabetes and many others, and autism spectrum disorder is only one among a list. Just how “common” mitochondrial disease is in autistic individuals, remains to be determined, and journalist David Kirby’s pronouncing the new study as “revolutionary” news in the Huffington Post seems characteristically overstated:
…..we can now assume that classic mitochondrial “disease” desrcibed [sic] in this study (via mutations in maternal mitochondrial DNA) and mild mitochondrial “dysfunction” found in Hannah and others (via mutations in paternal nuclear DNA) are both associated with increased risk for autism.
And we can also now assume that neither form of mitochondrial disorder is rare. Moreover, whether the low cellular energy originates in mitochonrial [sic] DNA or nuclear DNA mutations, either way it could confer increased risk for autism.
That would mean a significant number of children between the ages of 1 and 2 who are walking around right now, potentially vulnerable to autistic regression triggered by some acute immune stressor – whether vaccine related or not.
While Kirby has previously used the first person singular (”In April, I reported that”) in this latest post, in these paragraphs he uses the first person plural (”we can now assume”). No longer are Kirby’s statements to be seen as the speculations of one journalist; they are now, through the use of that “we,” converted into, it seems, the views of people in general and, indeed, the assumptions of people in general (and Kirby includes quotations from scientists and other experts, including the Executive Director and CEO of the UMDF, Charles A. Mohan, Jr., in his post). It thus seems that Kirby is expressing the opinion of people in general, and not only the assumptions that he has made, and presented with his usual rhetorical aplomb.
Say you’re the parent of a child “between the ages of 1 and 2 who [is] walking around right now” and (due to an underlying mitochondrial disorder) “potentially vulnerable to autistic regression triggered by some acute immune stressor”. At this point in the sentence, Kirby slips in mention of vaccines, though these are not mentioned in the UMDF’s summary of the study. Take a good long look at your child “walking around right now,” it is suggested; something may send them into “autistic regression,” Kirby writes, and offers the ominous image of a vaccine, a shot (did someone just write “triggered”?) to make his point.
Kirby ends his post with a further ominous statement:
It would appear that far more lives are at risk for far more diseases (well beyond autism) than we ever imagined.
While a recent study has found that, in a sample of 341 adults diagnosed with autism, atypical autism, childhood disintegrative disorder, and Asperger syndrome, “nearly twice of what is expected in the general population,” autism is not a “disease” that puts one’s life at risk. Epilepsy was the cause of death most reported among the cohort of individuals in the study, as Translating Autism notes in a review of it. It seems that, once again, Kirby is trying to make and even to rebrand autism, and here to suggest that it is a life-threatening condition, like cardiovascular diseases or cancer; to say he’s describing more and more of what might be the causes of autism, while having less and less to say about what autism is itself.
A company called Carantech, Inc. seems to be working on an animal model that could show how autism may be connected to the other serious medical problems that you mention. It is surprising that this animal model isn’t being discussed in the autism community. Their patent does a pretty good job of explaining their working hypothesis:
http://www.freepatentsonline.com/y2006/0130161.html
This potential animal model for autism may do more to “rebrand” autism than anything Kirby writes.
Warning: David Kirby is not a scientist. Not is he an objective journalist. He is someone looking for any and all evidence to support his agenda. I await scientists’ interpretations of the article.
Yes yes yes yes yes yes yes ……Autism and many other diseases are caused by mutations in the mitochondria. There are many chemicals and toxins that can cause mutations in the mitochondria. However, there are a few that are cause more problems that others. Wanna guess which is one of the worse? You guessed it, Mercury. Here is a nice piece for your consideration on this subject:
http://tinyurl.com/69s2n2
Mercury, cadmium, and other heavy metals have a high affinity for sulfhydryl (-SH) groups, inactivating numerous enzymatic reactions, amino acids, and sulfur-containing antioxidants (NAC, ALA, GSH), with subsequent decreased oxidant defense and increased oxidative stress. Mercury induces mitochondrial dysfunction with reduction in ATP, depletion of glutathione, and increased lipid peroxidation; increased oxidative stress is common.
Remember that old lady in the commercial who said “It’s not wise to mess with mother nature” Or how about that Indian crying on a horse by a polluted river? Guess we’ve lost our way and have forgotten about those folks with the help of the Bush Clan and big corporate America. For more info, visit one of my favorite sites http://www.bodyburden.org
From reading the abstract and the UMDF’s summary, autism is just one among many disorders mentioned, and the question remains, how common are mitochondrial disorders in autistic individuals, specifically?
I’m sure I’ve mentioned this before, but my daughter (3.5 and diagnosed with autism) has been suspected of having a mito disorder. Her symptoms aren’t serious enough yet and tests results are indicative enough yet to warrant biopsies and all that goes into a diagnosis. She has been sick with the same symptoms since birth and we’ve spent over 20k in medical bills. So she’s sick. Just not “sick enough” yet. I hate that “yet” word.
I’ve been reading quite a bit on immunization standards and children with metabolic disorders and how vaccine induced fevers can cause more harm than good in some of these kids. The thing is, we don’t know yet how many kids are affected by mito or metabolic disorders and what causes some to be full blown disease and others to just be underlying with no symptoms. How safe are the vaccines for these kids and what could they do to these kids if vaccinated on the current schedules? The obvious is there: more studies (not by pharmaceutical people or money) need to be conducted because no one knows. Which leads me to a question…
How do they do studies of vaccine safety? Is it on other children in our country, other countries? Is it disclosed that these vaccines are being “tested” for safety on these kids? I have no idea HOW the testing happens (if it does because NOT A SOUL will answer my question about safety studies on vaccine effects and long-term benefits of immunizations of newborns or babies under 12 months old.). So does anyone know how the testing happens? And to who? Is it animals or kids? Both? Like I wouldn’t want to buy products made off the exploitation of child labor in other countries, I would hate to think my child is being vaccinated with immunizations tested on children in other countries with less understanding of what they are being given. Are the studies honest in all ways to their subjects?
Hi Laura –
How do they do studies of vaccine safety? Is it on other children in our country, other countries?
Many tests are done with children from several countries, and most involve a very significant number of children. This is a very good thing in that it can help eliminate localized bias, and is a testament to the relative infrequence of serious and immediate side effects.
I have no idea HOW the testing happens (if it does because NOT A SOUL will answer my question about safety studies on vaccine effects and long-term benefits of immunizations of newborns or babies under 12 months old.).
Brstpathdoc attempted to respond to a similar question (I think by you) on a previous thread. It seems to me that the current system is quite good at identifying minor problems, or acute problems, but only those that occur within a relatively narrow timeframe; and those to which researchers can currently identify as having possible mechanisms of causing problems.
It is relatively simple to detect if a fever develops, or likewise if a person develops encephalopathy and dies within a few days/weeks of getting a particular vaccine. When patients are revisited a year or more after vaccination, the focus is generally on if the patient has a sufficient antibody response.
Some of the problem, in my opinion is that the papers I have read regarding tests usually do not track neurological disorders, both as a matter of not looking for such side effects, as well as having insufficient time frames for searching for such side effects. By way of example, a full testing for such side effects of a the current implementation of a Hep B shot would involve waiting a full three years before a correlation with autism diagnosis could be seen. Likewise with advanced dates for DTaP, Hib, or even rotovirus.
Further complicating matters is that changes to vaccines, or their schedules are usually studied in comparison to existing vaccines or existing schedules. So, for example, when DTaP was licensed, it was studied for side effects against the DTP. It was found, in fact, that immediate and dire side effects were much lower with DTAP than DTP. Many years after licensure and millions of doses later, we have evidence that the DTAP may be able to produce persistent changes to the immune system far above creating immunity to the desired diseases.
The benifits seem clear; I have little doubt that adding vaccines to a two month well visit checkup has resulted in a decrease in the number of deaths or sicknesses from a variety of diseases in the very young. The dirty little secret you won’t see acknowledged in many places is that we don’t have a good mechanism for weighing the risks of such changes up and above the known risks of becoming infected.
- pD
pD,
I appreciate your thoughtful response. I’ll have to go back and look for the response you referred to. It likely was me that asked about safety studies but I must have missed the response.
Thanks!
@Laura, Here’s the response from brstpathdoc (who is a doctor) about “adverse reactions”:
http://www.autismvox.com/amanda-peet-says-something-sensible/#comment-464144
I do remember your mentioning that about your daughter—-I’m looking up some other info on testing for vaccine safety and will post/comment on that.
One point to note is that scientists have to report any reaction or effect, regardless of how “rare” or in how small a population something occurs.
Also, there’s a popular misunderstanding of the term “adverse reaction,” as noted in Do Vaccines Cause That:
http://www.autismvox.com/a-loose-tooth-language-and-vaccines/
Ditto Albert. Ditto.
I look forward to your post/comment on the testing procedures. It’s something I hadn’t thought of until recently as I’m asking for further testing of vaccines…who are they testing them on and do they know they are being used as test subjects?
Also, the few safety tests I’ve seen have not had any long term safety studies done that I can tell, so the only way they are considering a reaction is if it is immediately obvious and allergic in nature. Also, the Hep B doesn’t seem to have any newborn safety studies that I can tell. My child’s doctors refused to believe it was the vaccines (particularly Hep B) that caused my daughter’s fevers that lasted several weeks, rash from head to toe, vomiting, diarrhea and dehdyration. She was hospitalized for care after each of her vaccines and yet the doctors would not acknowledge any reaction. Would scientists have a greater sense of integrity or insight? I hope so, but it worries me when a medical community does not (in our experience with our doctors and children’s hospital).
” . . . the question remains, how common are mitochondrial disorders in autistic individuals, specifically?”
One indirect way of answering that would be to figure out how common HHV-6 infections are in autistic individuals because mitochondrial dysfunction seems to be associated with HHV-6.
(HHV-6 has been suggested as a potential trigger for autism by the director of the HHV-6 Foundation.)
This abstract discusses HHV-6B and mitochondria:
http://tiny.cc/55Ius
Any effects of vaccines on mitochondria would be acute, within a few days to perhaps a few weeks. Mitochondria undergo continuous replacement, a few percent per day (but usually at night). The longest lifetime mitochondria are in the CNS. In rats they last about a month, in humans it is likely somewhat longer, perhaps a few months.
The mitochondrial mutations observed in this study were mainly hetereoplastic, that is cells contained both mitochondria with the mutation and mitochondria without the mutation. These mitochondria were in blood cells, which derive from blood stem cells which over a lifetime multiply many times more than do somatic cells. It is not rare for people to lose a genetic defect from their blood stem cells as they age. What that means is that the stem cells with the genetic defect didn’t continue to replicate and were replaced by blood stem cells without the defect. They allude to this in the article, suggesting that some mothers may have been heteroplastic for the mitochondrial defect and lost that heteroplasty over time. The reason this happens is because stem cells with the defect don’t replicate as well and so over time good stem cells out replicate them and eventually replace them.
If you did happen to have a mitochondrial defect that was heteroplastic, putting your cells under sufficient metabolic stress to challenge those defective mitochondria to the point of failure might be an excellent therapy strategy. If all the defective mitochondria in a cell are destroyed, the only ones left are the non-defective ones. Periodic infections and fevers might be a natural mechanism to do that.
Hi Daedulus2u –
The mitochondrial mutations observed in this study were mainly hetereoplastic, that is cells contained both mitochondria with the mutation and mitochondria without the mutation. These mitochondria were in blood cells, which derive from blood stem cells which over a lifetime multiply many times more than do somatic cells.
Interesting stuff, but I’m feeling confused again. The study seems to indicate they were looking for ten ‘common’ mutations that could lead to defective mitochonrdrial function. If the loss of such mutations isn’t rare, I’m struggling to figure out how these particular mutations could be identified as common causes; i.e., how are they identifiable if they are lost to regeneration?
This is reminiscent (sp?) of a discussion I had on this board previously regarding CNVs versus environmentally acquired mutations, I can see pretty easily how acquired mutations could be lost to new cell generation, but not how a more global mutation could fall to the wayside. Likewise, I’m having trouble with acquired mutations accumulating to such a point that they are identifiable as problematic mutations, and not everyday mutations that we all tend to have.
Can you give us some more insight?
Thanks
-pD
@h6
How’s how immuno-agent coming that was being worked on a few years back that was supposed to target some of this stuff (eg. HHV6) you discuss? If memory serves it was something like IGF1 in combination with DAPTA. Thanks for any info.
lcm,
The HHV-6 Foundation’s site says this about treatment for HHV-6:
“The Foundation is actively working with drug companies to spur an interest in the development of new treatments for HHV-6. The Foundation has also funded extensive in-vitro testing on natural compounds or compounds that are already approved for other conditions.
Although they are not FDA-approved for treatment of HHV-6 infection, many doctors treat HHV-6 encephalitis with intravenous ganciclovir (Cytovene) or foscarnet (Foscavir). Ganciclovir is also available in an oral form (Valcyte ). In vitro studies have shown that cidofovir (Vistide) which is also approved for CMV retinitis, is more effective than either ganciclovir or foscarnet (DeClercq 2003, Long 2003). However it is not known how well cidofovir crosses the blood brain barrier.
Both foscarnet and cidofovir must be administered with a great deal of hydration to avoid kidney toxicity. Typically a full liter of water is given by IV before each dose. Probenecid is given with cidofovir to protect the kidney.
Valcyte (valganciclovir) is an antiviral pill that is turned into ganciclovir in the body. Because it is better absorbed than ganciclovir pills, it causes much higher levels of ganciclovir in the blood. It is manufactured by Roche pharmaceuticals. The drug is primarily used to treat cytomegalovirus infections, which is most common in transplant patients, however it has been shown in uncontrolled studies to effectively treat co-infection of HHV-6 and Chronic Epstein Barr virus. Stanford University researchers are undergoing a trial of Valcyte in a subset of CFS patients with elevated antibodies to HHV-6 and EBV. They call this condition Virus Induced CNS Dysfunction. (See info on Stanford Trial of Valcyte in VICD.)
In an in vitro study at The Rega Institute funded by the Foundation, the influenza antiviral and Parkinson’s drug, amantadine, generated a reproducible inhibition of HHV-6 replication, albeit at relatively high (subtoxic) concentrations. Researchers at the Rega institute also found lamotrigine, an anti-epileptic drug, was effective against HHV-6B but not HHV-6A (Naesens et al, 2006).”
http://www.hhv-6foundation.org/treatment.html
And Carantech, Inc., the company I mentioned in my first post, lists a number of “antibody therapeutics” that they are exploring. (See the link above.)
It’s all up in the air. The sooner we know one way or another if HHV-6 in involved in autism, the better.
@h6
Thanks very much for all that h6. Much appreciated. Can the HHV6 Foundation do a study on the adults with ASD and see how many have HHV6?
lcm,
All I know about the HHV-6 Foundation’s interest in autism is what I read on April 5th in Kent Heckenlively’s post on Age of Autism:
“About six weeks back I was given the name of a woman who had approached Generation Rescue. She has a foundation which is working on the theory that the Human Herpes Virus #6 (HHV-6) is the cause of chronic fatigue syndrome. This woman’s foundation often talked with the world’s top virologists who privately tell her their belief that HHV-6 is also implicated in multiple sclerosis, autism, and seizures. She didn’t have time to pursue HHV-6 in regards to autism, but thought we should be made aware of the theory.”
Mr. Heckenlively’s autistic daughter apparently was started on ganciclovir, the experimental treatment, even before they got the test results for HHV-6.
On April 14th, Mr Heckenlivey wrote:
“After one blood draw went awry and we finally got a sample to Viracor [a company that performs HHV-6 tests], three weeks after starting on ganciclovir. On Friday I got the result back. It was 100 copies, a weak positive reading.
Curiously, though, she showed no antibodies to HHV-6, suggesting an immune system issue. This puzzled our virologist until I mentioned again to him our belief that autistic children are immune-compromised. He acknowledged my point, but I don’t think he believes me yet.
So, what are the possibilities? After three weeks on the medication maybe it’s done a pretty good job at knocking the virus down? That is a reasonable assumption and to me the most likely one. I’m seeing some clinical improvements, but she often seems to have an up and down cycle over a month, so I’m not breaking out the champagne just yet.”
Unless I’ve missed it, Mr. Heckenlively hasn’t written anything else about HHV-6 since then.
His blog:
http://www.ageofautism.com/legal/index.html
Don’t tell me vaccines don’t do damage. My 3rd child had DTaP and had neuro reaction – repetitive movements, not turning towards voice, etc. – luckily it didn’t last forever and he is fine now. But no more DTaP – ever! The reaction was somewhat subtle but Dr. did say had he continued to receive DTaP reaction may have become permanent, which, let me tell you, looked like autism to me.