JAMA Confirms that Mitochondrial Dysfunction at Play in Autism

From the Journal of the American Medical Association:

Mitochondrial Dysfunction in Autism

1. Cecilia Giulivi, PhD;
2. Yi-Fan Zhang, BS;
3. Alicja Omanska-Klusek, MS;
4. Catherine Ross-Inta, BS;
5. Sarah Wong, BS;
6. Irva Hertz-Picciotto, PhD;
7. Flora Tassone, PhD;
8. Isaac N. Pessah, PhD

[+] Author Affiliations

1.
Author Affiliations: Department of Molecular Biosciences, School of Veterinary Medicine (Drs Giulivi and Pessah, Mr Zhang, and Mss Omanska-Klusek, Ross-Inta, and Wong), Departments of Public Health Sciences (Dr Hertz-Picciotto) and Biochemistry and Molecular Medicine (Dr Tassone), School of Medicine (Drs Hertz-Picciotto and Tassone), and Center for Children's Environmental Health and Disease Prevention (Drs Hertz-Picciotto and Pessah), and Medical Investigations of Neurodevelopmental Disorders Institute (Drs Hertz-Picciotto, Tassone, and Pessah), University of California, Davis.

Abstract

Context Impaired mitochondrial function may influence processes highly dependent on energy, such as neurodevelopment, and contribute to autism. No studies have evaluated mitochondrial dysfunction and mitochondrial DNA (mtDNA) abnormalities in a well-defined population of children with autism.

Objective To evaluate mitochondrial defects in children with autism.

Design, Setting, and Patients Observational study using data collected from patients aged 2 to 5 years who were a subset of children participating in the Childhood Autism Risk From Genes and Environment study in California, which is a population-based, case-control investigation with confirmed autism cases and age-matched, genetically unrelated, typically developing controls, that was launched in 2003 and is still ongoing. Mitochondrial dysfunction and mtDNA abnormalities were evaluated in lymphocytes from 10 children with autism and 10 controls.

Main Outcome Measures Oxidative phosphorylation capacity, mtDNA copy number and deletions, mitochondrial rate of hydrogen peroxide production, and plasma lactate and pyruvate.

Results The reduced nicotinamide adenine dinucleotide (NADH) oxidase activity (normalized to citrate synthase activity) in lymphocytic mitochondria from children with autism was significantly lower compared with controls (mean, 4.4 [95% confidence interval {CI}, 2.8-6.0] vs 12 [95% CI, 8-16], respectively; P = .001). The majority of children with autism (6 of 10) had complex I activity below control range values. Higher plasma pyruvate levels were found in children with autism compared with controls (0.23 mM [95% CI, 0.15-0.31 mM] vs 0.08 mM [95% CI, 0.04-0.12 mM], respectively; P = .02). Eight of 10 cases had higher pyruvate levels but only 2 cases had higher lactate levels compared with controls. These results were consistent with the lower pyruvate dehydrogenase activity observed in children with autism compared with controls (1.0 [95% CI, 0.6-1.4] nmol × [min × mg protein]−1 vs 2.3 [95% CI, 1.7-2.9] nmol × [min × mg protein]−1, respectively; P = .01). Children with autism had higher mitochondrial rates of hydrogen peroxide production compared with controls (0.34 [95% CI, 0.26-0.42] nmol × [min × mg of protein]−1 vs 0.16 [95% CI, 0.12-0.20] nmol × [min × mg protein]−1 by complex III; P = .02). Mitochondrial DNA overreplication was found in 5 cases (mean ratio of mtDNA to nuclear DNA: 239 [95% CI, 217-239] vs 179 [95% CI, 165-193] in controls; P = 10−4). Deletions at the segment of cytochrome b were observed in 2 cases (ratio of cytochrome b to ND1: 0.80 [95% CI, 0.68-0.92] vs 0.99 [95% CI, 0.93-1.05] for controls; P = .01).

Conclusion In this exploratory study, children with autism were more likely to have mitochondrial dysfunction, mtDNA overreplication, and mtDNA deletions than typically developing children.

David Kirby: The Growing List of Professionals Recognizing the Vaccine/Autism Connection

From David Kirby:

The List Keeps Growing
By David Kirby

It’s getting harder to keep up with the list of scientists, doctors, and public health officials who now believe that a vaccine-autism connection is at the least possible, and should be researched further.

Earlier this week, Dr. Peter Fletcher, former Chief Scientific Officer at the UK Department of Health was added. Now, eight more prominent researchers have joined the group. (See list below – they are the last eight names added).

These are the authors of the new study, “Mitochondrial Disease in Autism Spectrum Disorder Patients: A Cohort Analysis,” who did chart reviews on Hannah Poling and two dozen other young people with autism and mitochondrial dysfunction.

In my opinion, it could well prove to be one of the most significant autism studies published to date. (My Huffington Post article on this is HERE:

Mito disorders, which might affect 7-to-30 percent of all children with ASD, can predispose kids to developmental regression following a stressful trigger. Such a trigger might come from a febrile infection – or it could conceivably come from a vaccine reaction, the authors wrote.

“There might be no difference between the inflammatory or catabolic (breaking down of tissue) stress of vaccinations and that of common childhood diseases, which are known precipitants of mitochondrial regression,” they said.

And then they wrote this: “Large, population-based studies will be needed to identify a possible relationship of vaccination with autistic regression in persons with mitochondrial cytopathies (cellular disorders).”

And so, they get added to the list.

The list keeps changing in other ways. For example, late last spring it listed, “all three presidential candidates” (Obama, Clinton and McCain). Soon enough, that will be changed to US President, Secretary of State, and a pivotal and potentially filibuster-busting Senator from Arizona.

Another change: Before, the list said, “Autism researchers at Johns Hopkins University Medical Center.” Now, those people can be named, along with their colleagues: Investigators at the Cleveland Clinic and Massachusetts General Hospital. I have also listed a Harvard scientist who sits on an advisory panel of the federal Inter-Agency Autism Committee (IACC).

It makes you wonder how long the term “fringe” can seriously be applied to people who believe that this debate is not over.

Finally, keep your eye on the draft National Vaccine Plan at HHS, especially this January - right around the time the nation gets a new HHS Secretary and, reportedly, a new Director of the CDC – both of whom could potentially be added to the list, as well.

-----------------------------------------------

In 2008, the following groups and individuals have advocated, or at least considered, further study of a possible vaccine-autism connection:

1) Presidenti-Elect Barack Obama,
2) Sen. Hillary Clinton, Secretary of State Designee
3) Sen. John McCain, Senior Senator from Arizona and pivotal minority vote
4) Dr. Julie Gerberding, Director of the CDC
5) Dr. Bernadine Healy, Former Director of the NIH and President of the American Red Cross
6) Rep. Brad Miller, (D-NC), Chairman of the Subcommittee on Investigations and Oversight of the House Committee on Science and Technology
7) Members of the HHS Vaccine Safety Working Group
8) Officials at the CDC’s Immunization Safety Office who drafted the federal vaccine safety research agenda, the National Vaccine Plan
9) Medical personnel at the Vaccine Injury Compensation Program of HHS, who ordered federal compensation to Hannah Poling for her vaccine-associated autism.
10) Members of the CDC’s Clinical Immunization Safety Assessment Network (CISA)
11) America's Health Insurance Plans (AHIP), the national association representing nearly 1,300 companies covering more than 200 million Americans
12) Research grant making officials at Autism Speaks
13) Dr. Douglas Wallace, Professor of Molecular Medicine at the University of California, Irvine, Director of the UCI Center for Molecular and Mitochondrial Medicine in Genetics, and member of the Scientific & Medical Advisory Board of the United Mitochondrial Disease Foundation
14) Dr. Peter Fletcher, former Chief Scientific Officer at the UK Department of Health
15) Dr. Jon Poling, prominent neurologist and father to Hannah Poling
16) Dr. Isaac Pessah, Professor and Chair, VM: Molecular Biosciences,
Director, Center for Children’s Environmental Health, University of California, Davis, and member of the Strategic Planning Workgroup for Autism Spectrum Disorders of the federal Inter-Agency Autism Committee (IACC).
17) Dr. Martha Herbert, Assistant Professor, Pediatric Neurology Director, Transcend Research Program, Harvard Medical School, and member of the Strategic Planning Workgroup for Autism Spectrum Disorders of the federal Inter-Agency Autism Committee (IACC).
18) Dr. Geraldine Dawson, Chief Science Officer, Autism Speaks, and member of the Strategic Planning Workgroup for Autism Spectrum Disorders of the federal Inter-Agency Autism Committee (IACC).
19) Dr. Jacqueline R. Weissman, Cleveland Clinic Lerner College of Medicine
20) Dr. Richard I. Kelley, Department of Pediatrics, Johns Hopkins University Medical Center and Division of Metabolism, Kennedy Krieger Institute
21) Dr. Margaret L. Bauman, Department of Pediatrics and Learning and Developmental Disabilities Evaluation and Rehabilitation Services (LADDERS), Massachusetts General Hospital
22) Dr. Bruce H. Cohen, Neurological Institute and Pediatrics Institute, Cleveland Clinic
23) Dr. Katherine F. Murray, Genomic Department of Pediatrics and Learning and Developmental Disabilities Evaluation and Rehabilitation Services (LADDERS), Massachusetts General Hospital
24) Dr. Rebecca L. Mitchell, Genomic Medicine Institute, Cleveland Clinic
25) Dr. Rebecca L. Kern, Department of Pediatrics, Johns Hopkins University Medical Center and Division of Metabolism, Kennedy Krieger Institute
26) Dr. Marvin R. Natowicz, Cleveland Clinic Lerner College of Medicine


“HONORARY MEMBER”:

HHS Secretary Designee Tom Daschel, who said in November of 2002: “Mercury-based vaccine preservatives actually have caused autism in children.”

Looking for Mitochondrial Disorders In Your Autistic Child

So there has been much, "How do i know if my child has a mitochondrial disorder" discussion these days. Here is a blurb from David Kirby on the biomarkers to look for that could point toward mito dysfunction. Discuss them with your doctor.

"1) Mark Blaxill sent this to me. It is a sample list of some of the higher estimates of mitochondrial imbalances in autism samples. Most of these are elevated relative to a reference range.


1. 47% (elevated serum creatine kinase, Poling et al)

2. 38% (elevated plasma aspartate aminotransferase, Poling et al) vs. 22% in controls

3. 28% (elevated plasma lactate/pyruvate ratio, Correia et al)

4. 20% (elevated plasma lactate, Oliveiro et al)

5. 17% (elevate plasma lactate, Correia et al)

6. 13-16% (two hyperlactidemia markers, Oliveiro et al)

7. 65% - Shoffner (I need to check this abstract – DK)

2) Another ASD doctor, who does not specialize in mito disorders, went back and looked at blood work from his patient caseload in Jan 08. A high lactate/low pyruvate ratio is one marker (though a child who squirms during a blood draw can have elevated levels, though Poling and others try to control for false negatives)

This is what the pediatrician found:

168 total visits (consecutive)
147 different patients (consecutive)
67 had blood lactate done in clinic and sent stat to the local hospital (45.5% of patients)
21/67 had a blood lactate above the normal reference range (31.3%)

Blaylock on Mitochondria and Vaccines

Mitochondria and Vaccines
From Russell L. Blaylock M.D.

As the person who first proposed the microglial/excitotoxin hypothesis (JANA 2003;6(4): 21-35 and J. Amer Phys Surg 2004; 9(2): 46-51) I feel I should explain the connection between microglia/excitotoxicity and mitochondrail dysfunction. My hypothesis was confirmed two years later by Vargis, et al in which they demonstrated chronic levels of inflammatory cytokines and chemokines as well as microglia and astrocytic activation in the brains of 11 autistics from age 5 years to 44 years, even though they never mentioned excitotoxicity as a final mechanism. I wish to address the mitochondrial issue, which has become of major interest with the appearance of the Hannah Poling’s case.

In my original hypothesis, later expanded in a number of other articles, I explained that when the systemic immune system is overactivated, the brain’s special immune system, consisting of microglia and astrocytes, also becomes activated. The microglia normally remain in a quiescent state called ramified microglia. Upon activation, they swell, assume special immune receptors in their membranes and move within the extracellular space. In this activated state they act as immune presenting cells and can secrete a number of inflammatory chemicals, such as IL-1, IL-2, IL-6, IL-12 and IL-18, TNF-alpha, chemokines, complement and two excitotoxins called glutamate and quniolinic acid. They also generate a number of powerful free radicals and lipid peroxidation molecules.

A number of studies have shown that when you use powerful immune adjuvants, as used in vaccines (especially when combined), this inflammatory/excitotoxic reaction within the brain is maximized. With the first vaccine (or natural infection) the brain’s microglia are in a semi-activated stated called primed. If you re-vaccinate the animal or person within 1 to 2 months, these primed microglia overreact intensely, pouring out even higher levels of the excitotoxins, inflammatory cytokines and free radicals. Each subsequent set of vaccinations worsens this process.

These inflammatory/excitotoxic secretions damage the developing brain, which is undergoing its most active development at the very time the child is receiving 24 vaccines. This vaccine schedule exposes the child to a priming HepB vaccine at birth, 6 vaccines at age 2 months, then 5 vaccines at age 4 months, 7 vaccines at 6 months and finally 8 antigens at age one year. Each successive multi-dose barrage of vaccines intensely activates the brain’s microglial system and the microglia activate the astrocytes, which also secretes, inflammatory cytokines, free radicals and excitotoxins.

Experiments in which this pattern of immune stimulation is simulated using a vaccine adjuvant, demonstrate that it produces significant disruption of brain development. The greatest damage in these experiments is to the cerebellum and frontal lobes, which is also the primary sites of damage in autism. Further, food allergins also act as brain microglial activators, thereby worsening and prolonging the original immune/excitotoxic effect produced by the vaccines.

So, how does mercury play into all this. Mercury in extremely small concentrations (nanomolar concentrations) can activate microglia, trigger excitotoxicity and induce significant mitochondrial dysfunction. Blocking the glutamate receptors (that trigger excitotoxicity) also blocks most of the neurotoxic effect of mercury at these concentrations. That is, most of lower-dose effects of mercury in the brain are secondary to excitotoxicity. The mitochondria produce most of the energy used by neurons and a number of studies have shown that suppressing mitochondrial function by itself is not enough to alter brain function, but it is enough to magnify excitotoxic damage. That is, it is the excitotoxicity that is disrupting brain function and development.

A newer study has shown conclusively, that mitochondrial activation using a vaccine adjuvant not only suppresses mitochondrial function but that the damage cause by this mitochondrial suppression is actually produced by excitotoxicity. Blocking excitotoxicity completely blocks the microglial-induced neurotoxicity and mitochondrial damage cause by the vaccine.

A great number of studies have shown that activating the systemic immune system repetitively worsens neurological disorders caused by other things and can initiate neurodegeneration itself, that is prolonged. The inflammatory cytokines interact with glutamate receptors to dramatically increase excitotoxic damage. We know that autistic children have elevated CSF and blood levels of glutamate, which confirms the presence of the excitotoxic process.

Basically, what we see is a process triggered by sequential, massive vaccination that primes and then activates the brain microglial/astrocytic system, triggering the release of massive amounts of inflammatory cytokines, chemokines and excitotoxins. This suppresses the mitochondria and the resulting energy loss further worsening the excitotoxic damage. Because of continued immune activation systemically, both by food allergies and natural infections, the brain’s immune system remains in an active state, leading to suppression of brain pathway development and neural function. This is why the change in the vaccine policy beginning in the mid-1980s, triggered the epidemic of autism. The mercury just aggravated the process.

I warned a number of people and published my warning, that removing the mercury from vaccines would not stop the high incidence of autism, because it was just part of the picture. We must also appreciate that there are a great number of sources of mercury besides vaccine-mainly environmental and from dental amalgam.

For more information on this mechanism you can read my original articles on my website –www.russellblaylockmd.com. Also I have written more papers on my website under the heading -Information. All the information is free. I have several newer articles appearing in Medical Veritas and the Journal of Alternative Therapeutics in Health and Medicine.

Russell L. Blaylock, M.D.

HT: Sophia Lauren

WaPo Reports on Mitochondrial Disorders and Autism

Another article on John Shoffner's presentation.

I would like to call attention to the fact that mitochondrial disorders are not purely of genetic origin, but also the result of toxic injuries from ingredients found in vaccines like thimerosal and aluminum and also pesticides and medications like AZT.

I am of the opinion that one of the reasons that HHS didn't give Jon Poling a hearing on his daughter's autism/vaccine injury claims, and just conceded that her mito disorder plus vaccines triggered her autism, was that they knew he would be able to prove the whole process was started by her vaccines. His multiple hit theory that her first round of shots gave her the mitochondrial disorder and her last interacted with them to trigger the autism is probably right, and they know it, so best to keep part one of the process underwraps and still try to get away with calling it a 'rare genetic condition' even if they had to admit to the last part.

The media is apparently not ready to report that these mitochondrial dysfunctions that interact with vaccines to cause autism as in Hannah's case, can themselves be triggered by an earlier round of shots, but I am sure that someone will get bold and report it soon.

Things are changing faster and faster as Kent Heckenlively so eloquently expressed when he compared the fall of the 'no link' party line and it's CDC proponents to the exponentially speedy fall of communism.

BRING ON THE CONGRESSIONAL HEARINGS!

UPDATE: Boyd Haley, Ph.D. Chemistry Department Chair at the University of Kentucky checks in.

"The research of Dr. Jill James showing lower reduced glutathione levels in autistics is a very strong indication that these children are suffering from oxidative stress. Dr. Woody McGinnis has research that indicates this also. Low glutathione can be caused by many toxic insults , including viral, bacterial and heavy metal or organic toxicants. Old men with muscle wasting disease have low glutathione levels which can be treated with some effectiveness with melatonin according to a past publication. Melatonin reportedly (Dr. Bernie Rimland) was one item that helped many autistics. Basically, I think that treating glutathione production by appropriate (and I don’t know what that is at this time) supplementation and removing any toxicant involved would be the best approach towards improving these children." - Boyd Haley

and

"Regarding “the cause for mitochondrial disorders quest” just google or medline ‘mercury effects on mitochondria’. Researchers have made careers looking for genetic causes of mitochondrial disorders in certain patients without ever eliminating the likely possibility that these individuals are mercury toxic or toxic with some other heavy metal. Trust me, not one single genetic screen of individuals with mitochondrial disorder will have included a survey of the number of dental amalgams the individuals had---and mercury from amalgams accounts for about 80% of the total mercury body burden. Now, consider that 85% of dentists have abnormal porphyrin profiles that indicate they are mercury toxic as do a large percentage of autistic children. The site of inhibition of the porphyrin profile is on the inner mitochondrial membrane---so mercury is in the mitochondria and doing biological damage on porphyrin (or heme) synthesis and WE DON’T KNOW ALL OF WHAT ELSE IT IS DOING. But we do know that in tests both the citric acid cycle and the electron transport system (ETS) are dramatically inhibited by low levels of mercury." - Boyd Haley

Muscle Weakness Found in Some Autistic Children
By Serena Gordon
Washington Post
Sunday, April 13, 2008; 12:00 AM

SUNDAY, April 13 (HealthDay News) -- New research suggests that muscle weakness in a child with autism may point to an underlying genetic defect that's causing mitochondrial disease, which means the muscles don't get the energy they need.

Conversely, it's possible that the mitochondrial disease may also play a role in the development of autism, perhaps by preventing the brain from getting the energy it needs to perform properly, the researchers noted.

"In large studies of kids with autism, about 20 percent have markers of mitochondrial disease in the blood," explained Dr. John Shoffner, an associate professor of biology at Georgia State University and president of Medical Neurogenetics.

Shoffner recently completely a retrospective analysis of 37 children with autism spectrum disorders and found that 65 percent of these children -- children who had been referred to him because their doctors suspected additional problems -- had mitochondrial defects.

He was expected to present the findings April 13 at the American Academy of Neurology's annual meeting, in Chicago.

Mitochondria are found in every cell of the body, with the exception of red blood cells, according to the United Mitochondrial Disease Foundation (UMDF). Mitochondria are vital to survival, because they make oxygen available to cells and metabolize food into energy for cells to thrive. Defects in mitochondria can lead to cell injury, or even cell death, according to UMDF.

Symptoms of mitochondrial disease depend on which body system is affected but may include muscle weakness, loss of muscle control, poor growth, heart disease, diabetes, developmental delays, an increased risk of infection and more.

Shoffner said that the mitochondrial energy production system is the only one in the body that requires two genomes to work -- genes inherited from both the mother and the father, and genes exclusively from the mother. "To make this system work, it requires a lot of genes. Hence the opportunity for lots of problems," said Shoffner, who added that there are several hundred known mitochondrial disorders.

Twenty-four (65 percent) of the children included in this study had genetic defects in their skeletal muscles. However, that doesn't mean that 65 percent of children with autism likely have mitochondrial disease. This was a select population of kids with autism, ones that had specifically been referred, because their doctors suspected a problem.

But, Shoffner pointed out that as many as one in five youngsters with autism spectrum disorders have shown signs of mitochondrial disease.

"If you're talking about 20 percent of kids with autism, that's a whole lot of children, and may represent an important segment of the autism spectrum disorder population. And we may be getting a foothold into the underlying cause of autism spectrum disorders," he said, adding, "This is a really important step forward that lets us put effort into understanding the mechanisms of disease."

"This study is a call to action. We need to know what is the real prevalence of mitochondrial conditions in children with autism," said Geraldine Dawson, chief science officer for Autism Speaks. "The more we can identify these subgroups of kids, the more we're going to parse apart the many forms of autism. This gives us clues to etiology."

"If we find that mitochondrial disease is a prevalent condition, having a better understanding of the kinds of symptoms that children may show if they have it might be helpful for parents," she said.

Shoffner said these findings may also open up new avenues of research into potentially more effective treatments for the future.

...

SOURCES: John M. Shoffner, M.D., associate professor, biology, Georgia State University, and president, Medical Neurogenetics, Atlanta; Geraldine Dawson, Ph.D., chief science officer, Autism Speaks; April 13, 2008, presentation, American Academy of Neurology annual meeting, Chicago

Neurologist Finds that More Than 60% of His Autistic Patients Have Mitochondrial Disorders

"Shoffner wanted to see if he could identify the underlying genetic mechanisms that might explain this link.

He evaluated genetic samples and clinical information gathered on 37 children diagnosed with autism who had been evaluated at his clinic for mitochondrial disease.

They found more than 60 percent of these children had mitochondrial defects."

Now this is not a random sample and is much higher than the Portuguese study (20%), so until these numbers start to settle to a smaller ball park than 'between 20 and 60 percent' in studies with better sampling, we should not hold too closely to this number. But if they do end up settling near Shoffner's experience, it will be safe to say that CDC's claims of 'rare' are really, really wrong and probably criminal.

New autism finding hope
Date: 13/04/2008

CHICAGO, April 13 (Reuters) - U.S. researchers have found a genetic link between autism and a muscle-weakening disorder known as mitochondrial disease, they said on Sunday, in a finding that may open new avenues of research into the causes of autism.

"Recent studies have suggested that as many 20 percent of patients with autism have markers for mitochondrial disease," said Dr. John Shoffner, a neurologist and geneticist at Medical Neurogenetics in Atlanta, who presented his findings at the American Academy of Neurology meeting in Chicago.

"There has really not been much work done so far to push that issue," Shoffner said in a telephone interview.

Mitochondrial diseases are a set of genetic disorders in which energy-producing structures in cells are impaired. The disease is often triggered by an illness, such as a high fever, which can result in severe muscle weakening.

Shoffner wanted to see if he could identify the underlying genetic mechanisms that might explain this link.

He evaluated genetic samples and clinical information gathered on 37 children diagnosed with autism who had been evaluated at his clinic for mitochondrial disease.

They found more than 60 percent of these children had mitochondrial defects.

Shoffner said the finding needs to be confirmed in other studies, but it does help to validate the hypothesis of a link between the two conditions in a subset of patients.

"This is a fundamental first step," Shoffner said in a telephone interview. "This gives us a great foothold for moving forward with this population -- asking better, more precise questions."

GEORGIA CASE

No one knows what causes autism, but researchers think it is likely that several genes contribute.

Some autism advocates have seized on the case of a Georgia girl with a rare mitochondrial disease and autism-like symptoms who won federal compensation in a case arguing a vaccine led to her condition.

Government health officials say there is no scientific evidence to suggest that vaccines cause autism, which is part of a spectrum of disorders that can have relatively mild symptoms or can severely disable a child by interfering with speech and behavior.

Shoffner said most children with autism spectrum disorders do not have recognizable abnormalities in mitochondria, but a group of these children have significant defects.

"We are opening avenues of additional research into autism spectrum disorders and new ideas about what might be causing these disorders to develop," he said.

The U.S. Centers for Disease Control and Prevention estimates that about one in every 150 U.S. children has autism or a related disorder such as Asperger's syndrome, which is marked by mild social awkwardness.

Several studies have suggested that genes involved with communication pathways in the brain may contribute to autism, and Shoffner thinks it is possible that cells with impaired ability to convert food into energy may play a role.

"It certainly sits at a very important place in cellular metabolism that can significantly alter neuronal (nerve cell) development," he said.

The United Mitochondrial Disease Foundation Checks In on Autism

How exciting would it be for Mito docs to show up at Autism One and start talking with DAN docs. When two different parts of medicine figure out they are connected, that is when real connections and discoveries take place.

So glad that everyone is ignoring the IOM's recommendation to stop looking into this line of inquiry.

Isn't it about time the IOM retracts their 2004 decision? They are starting to look a little silly at this point.

UMDF Statement on the Connection Between Mitochondrial Disease and Autism

PITTSBURGH, April 11 /PRNewswire-USNewswire/ -- The United Mitochondrial Disease Foundation released the following statement from its executive director and CEO, Chuck Mohan, in light of the National Vaccine Advisory Committee's (NVAC) meeting of its Vaccine Safety Working Group and recent published reports of possible links between mitochondrial disorders and autism.

"Recent published reports about the potential links between mitochondrial disorders and autism demonstrate the urgent need for more research into mitochondrial disease, a devastating and often fatal illness.

"Mitochondrial dysfunction has also been implicated in Alzheimer's Dementia, Parkinson's disease, Huntington's disease, heart disease and diabetes.

"Mitochondrial disease is not rare. Researchers estimate that every 15 minutes a child is born with mitochondrial disease or will be diagnosed with mitochondrial disease by the age of 10. Most affected children do not live beyond their teenage years.

"The National Institutes of Health currently spends about $11.8 million on research into mitochondrial-related research -- with only about one third of that earmarked for primary mitochondrial disease research. That is less than 1/1000 of one percent of NIH's $29B annual budget. That is why the United Mitochondrial Disease Foundation supports the effort by the National Institutes of Health to place mitochondrial disease research on an NIH roadmap.

"Mitochondrial disease deprives the body of energy making it difficult to function properly. It can affect any organ of the body and at any age. The brain may be impaired, vision may be dim, muscles may twitch or may be too weak to allow the body to walk or write, the heart may be weakened, and the ability to eat and digest food can be compromised.

"Finding the cause of and cure for mitochondrial disease would not only alleviate the suffering of families around the world, it would also unlock the door to a world of scientific knowledge and could help lead the way to possible treatments for many other diseases."

Jon Poling: Mitochondrial Dysfunction Not Rare In Autism

Dr. Poling suggesting medically defining "Mitochondrial Autism". I have been calling it "Poling Syndrome".

No matter what it is called, "what Hannah has" has been determined by HHS to be a vaccine injury. It is time for the medical community to define it, find what the percentage of kids with it are, screen for it and catch it before it descends into the "symptoms of Autism".

And if the medical authorities won't hear it from me, hear it from Jon Poling:

"As a neurologist, I have cared for those afflicted with SSPE (a rare but dreaded neurological complication of measles), paralytic polio and tetanus. If these serious vaccine-preventable diseases again become commonplace, the fault will rest solely on the shoulders of public health leaders and policymakers who have failed to heed the writing on the wall (scribbled by my 9-year old daughter)."

Reform the vaccine schedule before everyone abandons it.

Father: Child's case shifts autism debate
By Jon S. Poling
For the Journal-Constitution
Published on: 04/11/08

Autism in the U.S. has reached epidemic levels, at 1 in 150 children. Dr. Julie Gerberding, director of the Centers for Disease Control and Prevention, has recently upgraded autism to "an urgent health threat." The most contentious issue of the autism debate is the link to routine childhood vaccines. My daughter's case, Hannah Poling v. U.S. Department of Health and Human Services, has changed this debate forever. Hannah has pointed us in a new and promising direction —- the mitochondria.

On Nov. 9, 2007, HHS medical experts conceded through the Department of Justice that Hannah's autism was triggered by nine childhood vaccinations administered when she was 19 months of age. This concession was granted without any courtroom proceedings or expert testimony, effectively preventing any public hearing discussing what happened to Hannah and why. Contrary to some reports, the Special Masters, "judges" who preside over the "vaccine court," did not issue a decision.

Four months later, on March 6, with trepidation my wife, Terry, and I stepped forward to announce this news —- providing hope and awareness to other families. The HHS expert documents that led to this concession and accompanying court documents remain sealed, though our family has already permitted release of Hannah's records to those representing the almost 5, 000 other autistic children awaiting their day in vaccine court.

Mitochondria key

To understand Hannah's case, it is important to understand mitochondria, which act like batteries in our cells to produce energy critical for normal function. Because the government's concession hinged on the presence of Hannah's underlying medical condition, mitochondrial dysfunction, some claim the decision is relevant to very few other children with autism. As a neurologist, scientist and father, I disagree.

Emerging evidence suggests that mitochondrial dysfunction may not be rare at all among children with autism. In the only population-based study of its kind, Portuguese researchers confirmed that at least 7.2 percent, and perhaps as many as 20 percent, of autistic children exhibit mitochondrial dysfunction. While we do not yet know a precise U.S. rate, 7.2 percent to 20 percent of children does not qualify as "rare." In fact, mitochondrial dysfunction may be the most common medical condition associated with autism.

Biological markers

Although unlikely, if the Portuguese studies are incorrect and mitochondrial dysfunction were found to be a rarity occurring in less than 1 percent of all autism, it would still impact up to 10,000 children (250,000 worldwide), based on current estimates that 1 million people in the U.S. (25 million worldwide) have autism. If, on the other hand, the research showing that 7.2 percent to 20 percent of children with autism have mitochondrial dysfunction is correct, then the implications are both staggering and urgent.

Autism researchers do not currently understand whether mitochondrial dysfunction causes autism or is simply a secondary biological marker. Autism clearly has many different causes, and should really be separated into multiple autism(s). I propose that we clearly identify and research the subpopulation term of "mitochondrial autism," which is distinguished by its unique biological, but not genetic, markers.

Based on what we know now, it is time to follow the prestigious Institute of Medicine 2004 report regarding autism and vaccines:

"Determining a specific cause (for autism) in the individual is impossible unless the etiology is known and there is a biological marker. Determining causality with population-based methods requires either a well-defined at-risk population or a large effect in the general population."

A paradigm shift

When the IOM report was published, mitochondrial dysfunction defining an autistic subpopulation was not firmly established. Today there is no doubt that mitochondrial dysfunction represents a distinct autism subpopulation biological marker. I urge health officials and the IOM to embrace their own report and pursue this breakthrough in the science of autism. National public health leaders, including those at CDC, must now recognize the paradigm shift caused by this biological marker with regard to their current position of dispelling a vaccine-autism link.

In light of the Hannah Poling concession, science must determine more precisely how large the mitochondrial autism subpopulation is: 1 percent, 7.2 percent, 20 percent?

Based on the 2004 IOM analysis, if the mitochondrial autism subpopulation is found to be relatively uncommon, then all conclusions from prior epidemiological studies refuting an autism-vaccination link must be discarded. New studies then need to be performed exclusively with the mitochondrial subpopulation. If mitochondrial autism turns out to be common, then we could re-analyze the data from prior studies to determine if these studies were powered sufficiently based on a predicted effect size. If not powered appropriately, the conclusion refuting an autism-vaccine link would again have to be rejected. These statistical concepts are basic.

The current vaccine schedule, co-sponsored by the CDC and the American Academy of Pediatrics, injures a small but significant minority of children, my daughter unfortunately being one of those victims. Every day, more parents and some pediatricians reject the current vaccine schedule. In an abundance of caution, meaningful reform must be performed urgently to prevent the re-emergence of serious diseases like polio or measles.

Need for research

As a neurologist, I have cared for those afflicted with SSPE (a rare but dreaded neurological complication of measles), paralytic polio and tetanus. If these serious vaccine-preventable diseases again become commonplace, the fault will rest solely on the shoulders of public health leaders and policymakers who have failed to heed the writing on the wall (scribbled by my 9-year old daughter).

The mitochondrial autism scenario that my daughter has so eloquently painted has the CDC and public health experts logically cornered. Denial and fear tactics won't close Pandora's Box. Whether we find that mitochondrial autism is rare or common, there is urgent research left to be done to fully understand the interrelationship of vaccines, autism and mitochondria.

Reform of the vaccine schedule will be an important part of the solution, whether vaccines play a major or minor role in autism. Our public health agencies and programs need a reconstruction plan. Day one of the reconstruction hopefully starts at the Vaccine Safety Advisory Committee's Working Group, to be held at HHS headquarters today in Washington.

Dr. Jon S. Poling is a practicing neurologist in Athens and clinical assistant professor at the Medical College of Georgia.

Julie Gerberding Admits on CNN that Vaccines can Trigger Autism

This weekend Julie Gerberding, the head of the CDC, appeared on Dr. Sanjay Gupta's show, House Call, and explained that vaccines can trigger autism in a vulnerable subset of children. This is the claim that parents like me have been making since at least the 80's, and have been dismissed and even mocked for making it.

But no one in the main stream media seems to have noticed. Not even CNN. Not even Dr. Gupta who was sitting right in front of her.

[Video updated 4/2/08]





Apparently, if you dress in soft pink and speak in dulcet, reassuring tones, you can indict yourself in the biggest international health crisis of the times and not even your interviewer will notice.

It is time for Dr. Gerberding to be forced to give cogent answers to the difficult questions that it is her responsibility to truthfully address. From all I have seen, it will take an act of Congress to do it.

I am joining Hannah Poling's parents in calling for the immediate release of the Poling case documents, and calling for congressional hearings into the autism cases in the Vaccine Injury Compensation Program.

This obfuscation and double speak must end.


*For more on this interview, read these:

An Invitation to Julie Gerberding to Help Her Find the Missing Information on Autism

Wait! Did Julie Gerberding Just Admit that Vaccines Trigger Autism!?

Wait! Did Julie Gerberding Just Admit that Vaccines Trigger Autism!?

I think that she did!

She could not have talked around it or downplayed it more... but she said it.

I only saw the video on CNN's web site, but Kirby found the transcript of the whole show.

I am gonna dig through the transcript and get back to you.. in the mean time:

UPDATE: She did. Let's go to the tape.

CNN, CDC, and Some Truth
Posted March 29, 2008 | 02:20 PM (EST)
Huffington Post

It was a big morning in Atlanta today. In case you missed CDC Director Dr. Julie Gerberding this morning on CNN's "House Call with Dr Sanjay Gupta," it was rather interesting:

If I have read the transcript below correctly, Dr. Gerberding is saying that, yes, in some mitochondrial disorder cases, vaccines can be the trigger that causes "symptoms that have characteristics of autism." So, Dr. Gerberding admits a link -- but then denies that it is a link to autism.

The only problem with this line of argument is that I know for a fact that Hannah, as well as the kids in the new unpublished mito study were, as one doctor told me, "plucked right from autism clinics. They all have autism, there is no question of that."

JULIE GERBERDING, DR., CDC DIRECTOR: "Well, you know, I don't have all the facts because I still haven't been able to review the case files myself. But my understanding is that the child has a -- what we think is a rare mitochondrial disorder. And children that have this disease, anything that stresses them creates a situation where their cells just can't make enough energy to keep their brains functioning normally. Now, we all know that vaccines can occasionally cause fevers in kids. So if a child was immunized, got a fever, had other complications from the vaccines. And if you're predisposed with the mitochondrial disorder, it can certainly set off some damage. Some of the symptoms can be symptoms that have characteristics of autism."

So, complications from vaccines can set off damage that causes characteristics of autism (just not autism itself). I don't believe I have ever heard that from a CDC official before, though that doesn't mean they never said it.

At the same time, this language does not quite jive with what Director Gerberding told reporters just over three weeks ago on a conference call:

"Let me be very clear that (the) government has made absolutely no statement about indicating that vaccines are a cause of autism. That is a complete mischaracterization of the findings of the case, and a complete mischaracterization of any of the science that we have at our disposal today. So I think we need to set the record straight on that."

I guess it all depends on what the meaning of the word, "cause," is.

The CNN interview this morning with Sanjay Gupta continues:

GUPTA: Are we ready to say right now that childhood vaccines do not cause autism?

GERBERDING: We can say absolutely for sure that we don't really understand the causes of autism. We've got a long way to go before we get to the bottom of this.

GUPTA: And you are comfortable saying that with everything we know?

GERBERDING: I'll never be comfortable with everything we know. I mean, I think we have to have an open mind about this. We know that there is very little chance that something related to a vaccine is going to cause a serious problem for a child.

Amid the usual "vaccines save lives" answer to questioning if it's possible that childhood vaccines could cause autism, there is some new and interesting rhetoric in the CDC Director's statements:

To wit:

"Set off some damage"

"Have an open mind"

"We don't know"

"Get to the bottom" of vaccines and autism.

"Ill never be comfortable"

"Very little chance" - instead of "there is no evidence"

"Something related to A vaccine" - (as opposed to several vaccines at once)

This seems like news to me, but I could be wrong. At the least, I think it is interesting, and worthy of follow up, should anyone in the media be able to talk with Dr. Gerberding. For some reason, she doesn't return my calls.

More on Mitochondrical Disorders from the Clevland Clinic

Since the Poling's press conference three weeks ago, we have been hearing from health authorities like Julie Gerberding and Anne Schuchat that Hannah's mitochondrial disorder was genetic and rare.

David Kirby's most recent article let us know that the CDC has known since at least March 11th that Hannah's case is not at all rare, and famed The Cleavland Clinic here informs us that mito disorders are not all genetic, but can be caused by toxins.

Which leads us back to the same question as always in dealing with CDC officials... are they incompetent, or are they liars?

I have put the relevant pieces of information in bold.

Myths and Facts About Mitochondrial Diseases

Myth
All mitochondrial diseases are known by acronym abbreviations (e.g., MELAS, MERRF, NARP, LHON).

Fact
Acronyms were commonly used when these disorders were first described. Today, the naming of mitochondrial disorders is evolving. Mitochondrial disorders are currently named by any of the following methods:

* By acronym descriptions (still in use although most people with a mitochondrial disorder do not have an "acronymic-named" disorder)
* By a name based on a person who described the disease
* By a name based on a specific genetic mutation
* By a name based on a microscopic description of tissue, or
* By a name based on the deficient enzyme

It is important to note that the labels given this disorder do not, in and of themselves, predict the long-term outcome or alter treatment.

Myth
Mitochondrial diseases are inherited only from your mother.

Fact
The current thinking is that most mitochondrial diseases are the result of one or more complex inheritance patterns. Most mitochondrial diseases are the result of mutations (changes) in DNA located in the nucleus of the cell. Only mitochondrial disorders caused by mutations in the mitochondrial DNA (a specific structure in living cells, located outside the nucleus) are inherited exclusively from mothers.

Another source of mitochondrial disorders that affects a large percentage of patients is poorly functioning mitochondria that become that way because of:

* another disease process (including other chromosomal disorders)
* exposure to toxins or viruses
* other inherited genetic mutations that are not disease-causing until "triggered" by some other genetic factor

Myth
Mitochondrial disease is a childhood disease.

Fact
Although mitochondrial disorders are commonly seen in infants and children, they can occur at any age.

Myth
An individual with mitochondrial disease has mental retardation, growth problems, and/or seizures.

Fact
Only some individuals have these developmental problems. Patients' symptoms can range from extremely mild to severe, can involve one or more body systems, and can emerge at any age. The brain, muscles, heart, liver, nerves, eyes, ears, and kidneys are the organs and tissues most affected. Most patients' symptoms fluctuate over the course of their illness -- patients at some times experience no or few symptoms, and at other times have many and/or severe symptoms. Even family members with the same disorder can experience vastly different symptoms.

Myth
Since mitochondrial diseases are incurable, no treatments can be given to these patients.

Fact
Even though these disorders are long term and incurable, treatments are available. Early treatment of symptoms can reduce their impact and limit further disability. Avoiding certain medications and stressful situations that worsen symptoms is also helpful. Certain medications and supplements may improve mitochondrial disease-related symptoms -- just as they do for other incurable diseases -- such as diabetes and emphysema.

Myth
Patients with mitochondrial disease all have elevated lactic acid levels in their blood.

Fact
An elevated lactic acid level, along with other symptoms, typically does indicate a mitochondrial problem and requires further investigation. However, elevated lactic acid levels are not seen in all types of mitochondrial diseases. In making the diagnosis, your doctor will look for other signs of mitochondrial disorders in blood, urine, and spinal fluid samples.

Myth
A muscle biopsy is the "gold standard" for diagnosis of mitochondrial disease.

Fact
Although the muscle biopsy is a powerful diagnostic tool, it should not be considered a "gold standard." Examination of a biopsy includes microscopic evaluation, enzyme testing, and genetic testing. Although all U.S. labs that offer muscle biopsy meet strict laboratory guidelines, there is no agreed-upon standard approach for enzyme testing. Furthermore, a muscle biopsy with full analysis costs well over $10,000 and poses both surgical and anesthetic risks. In some patients, the diagnosis can be made based on clinical symptoms and a positive blood test (identifying a genetic mutation) or a combination of clinical findings and other non-invasive testing -- in either case, a muscle biopsy is not necessary. Finally, since biopsy results usually do not alter the long-term outcome or treatment considerations, some specialists and patients choose to treat without the need for a muscle biopsy.

Myth
A muscle biopsy is a muscle biopsy no matter where and how it is done.

Fact
Muscle removed for biopsy can be tested in many ways. For example, enzyme testing can be done on either ground-up muscle or on mitochondria extracted from muscle. Testing on extracted mitochondria is performed in only a few medical center laboratories and must be performed immediately. This procedure is known as a "fresh biopsy." In an alternative procedure, called a "frozen biopsy," the muscle is quickly cooled and stored at -80 degrees Celsius for testing at an outside facility. The scientific community is currently debating the advantages of testing "fresh vs. frozen" mitochondria. Some evidence indicates that the "fresh biopsy" may be the superior method. Other types of mitochondrial testing of the muscle biopsy may need to be conducted; a limited number of laboratories offer such testing.

For additional information on mitochondrial diseases, contact:

The United Mitochondrial Disease Foundation
8085 Saltsburg Road, Suite 201
Pittsburgh, PA 15239
412.793.8077
www.umdf.org

The Mitochondrial Medicine Society
www.mitosoc.org

HT: MomResearch

The Study That FINALLY Got The CDC to Pay Attention

Last night we learned from David Kirby that the CDC is actually waking up to the vaccine/autism connection because of the recent revelation of previously missing middle man Mr. Mitochondria.

Here is the study that was the slap in the fact that has been so badly needed for so long:

Epidemiology of autism spectrum disorder in Portugal: prevalence, clinical characterization, and medical conditions

Guiomar Oliveira MD PhD, Centro de Desenvolvimento da Criança, Hospital Pediátrico de Coimbra; Assunção Ataíde BSc, Direcção Regional de Educação do Centro Coimbra;
Carla Marques MSc, Centro de Desenvolvimento da Criança, Hospital Pediátrico de Coimbra; Teresa S Miguel BSc, Direcção Regional de Educação do Centro, Coimbra;
Ana Margarida Coutinho BSc, Instituto Gulbenkian de Ciência, Oeiras; Luísa Mota-Vieira PhD, Unidade de Genética e Patologia moleculares, Hospital do Divino Espírito Santo, Ponta Delgada, Açores; Esmeralda Gonçalves PhD; Nazaré Mendes Lopes PhD, Faculdade de Ciências e Tecnologia, Universidade de Coimbra; Vitor Rodrigues MD PhD; Henrique Carmona da Mota MD PhD, Faculdade de Medicina, Universidade de Coimbra, Coimbra; Astrid Moura Vicente PhD, Instituto Gulbenkian de Ciência, Oeiras, Portugal.
*Correspondence to first author at Hospital Pediátrico de Coimbra, Av Bissaya Barreto, 3000-076 Coimbra, Portugal. E-mail: guiomar@hpc.chc.min-saude.pt

The objective of this study was to estimate the prevalence of autistic spectrum disorder (ASD) and identify its clinical characterization, and medical conditions in a paediatric population in Portugal. A school survey was conducted in elementary schools, targeting 332 808 school-aged children in the mainland and 10 910 in the Azores islands. Referred children were directly assessed using the Diagnostic and Statistical Manual of Mental Disorders (4th edn), the Autism Diagnostic Interview–Revised, and the Childhood Autism Rating Scale. Clinical history and a laboratory investigation was performed. In parallel, a systematic multi-source search of children known to have autism was carried out in a restricted region. The global prevalence of ASD per 10 000 was 9.2 in mainland, and 15.6 in the Azores, with intriguing regional differences. A diversity of associated medical conditions was documented in 20%, with an unexpectedly high rate of mitochondrial respiratory chain disorders.

David Kirby Drops Another Bomb: Autism Risk May Be 1 in 50

Of the thirty kids with regressive autism that were screened, 100% of them had the same biochemical imbalances as Hannah Poling.

All 30.

100%

Hannah is in no way, rare.

"The biochemistry of 30 children was studied intensively, and in each case, the results showed the same abnormalities as those found in Hannah Poling, participants said. Each child had moderate elevations or imbalances in the exact same amino acids and liver enzymes as Hannah Poling."

And... (I can't even believe that I am typing these words) on the conference call that Kirby is writing about the CDC was discussing adjusting the vaccine schedule to make it safer.

Keep reading...

UPDATE: Kirby offers bullet points to help us wrap our heads around all the info here:

I realize my Huffington essay was rather long and complicated. Here is a brief synopsis of just SOME of the larger points raised in the piece. I will probably alter this a little, but it hits most of the main topics. Please feel free to circulate - DK

● Up to 1 in 50 children (2%) may have a genetic mutation that puts them at risk for mitochondrial dysfunction.

● Up to 20% of all children with autism may have an underlying mitochondrial dysfunction

● Children with mitochondrial dysfunction are more likely to regress into autism between the ages 1 and 2 years, if they have fever or illness from viral infections or vaccines.

● The CDC is aware of this difficult situation and is taking measures immediately to address the current national vaccine schedule.

● The genetic susceptibility for mitochondrial dysfunction in autism is inherited through the father, not the mother, as previously thought, and is not rare at all.

● The DNA mutation might not be enough in itself to confer cellular dysfunction, and many doctors believe there is an environmental trigger as well.

● They note that thimerosal, mercury, aluminum, pollution, pesticides, medicines and prenatal alcohol exposure have all been shown to damage mitochondria.

● Other doctors believe that a corn-byproduct based diet in America has put children in a constant inflammatory state, thus making the DNA mutation more pathogenic.

● While some children with mitochondrial dysfunction regress into autism following fever and illness from a viral infection; other kids, like Hannah Poling, clearly regress following a reaction to vaccines.

● The exact percentage of people with vaccine induced autism is unknown. But even a 1% rate could mean 10,000 Americans with vaccine related autism, at a cost of many billions of dollars for lifetime care.

The Next Big Autism Bomb, Are 1 in 50 Kids At Risk?
Posted March 26, 2008 | 09:30 PM (EST)
David Kirby
Huffington Post

On Tuesday, March 11, a conference call was held between vaccine safety officials at the US Centers for Disease Control and Prevention, several leading experts in vaccine safety research, and executives from America's Health Insurance Plans, (the HMO trade association) to discuss childhood mitochondrial dysfunction and its potential link to autism and vaccines.

It was a sobering event for all concerned, and it could soon become known as the Conference Call heard 'round the world.

The teleconference was scheduled by a little known CDC agency called the Clinical Immunization Safety Assessment (CISA) Network, a consortium of six research centers working on "immunization-associated health risks," in conjunction with the CDC's Immunization Safety Office and the health insurance lobby -- whose companies cover some 200 million Americans.

The hot topic of the day was mitochondria - the little powerhouses within each cell that convert food and oxygen into energy for use by the body. Recent news events have implicated mitochondria in at least one case of regressive autism, following normal development.

Some researchers on the call reported that mitochondrial dysfunction is probably much more common than the current estimate of 1-in-4,000 people. The potential implications for autism, then, are staggering.

"We need to find out if there is credible evidence, theoretically, to support the idea that childhood mitochondrial dysfunction might regress into autism," one of the callers reportedly told participants.

"THE CLOCK IS TICKING"

One person on the call (those interviewed for this article asked to remain anonymous) told me that, "the CDC people were informed, in no uncertain terms, that they need to look into this issue immediately, and do something about it." The clock is ticking, they were told, and if they don't respond, the information will be made public.

Still, the doctor said, he was enormously impressed by the "seriousness" with which CDC officials treated the possibility of a link between mitochondria, autism and possibly vaccines as well.

In the recent landmark Hannah Poling case, filed in Federal "Vaccine Court," officials conceded that Hannah's underlying mitochondrial dysfunction was aggravated by her vaccines, leading to fever and an "immune stimulation that exceeded metabolic reserves."

But on March 6, CDC Director Dr. Julie Gerberding claimed that Hannah's case was a rare, virtually one-of-a-kind incident with little, if any relevance to the other 4,900 autism claims currently pending in the court -- or to any other case of autism for that matter.(There were conflicting accounts about whether Gerberding was on the call or not).

Since then, however, Dr. Gerberding and other CDC officials were made aware of a Portuguese study, published last October, which reported that 7.2% of children with autism had confirmed mitochondrial disorders. The authors also noted that, "a diversity of associated medical conditions was documented in 20%, with an unexpectedly high rate of mitochondrial respiratory chain disorders."

"Apparently, the Portuguese study really got their attention," one of the participants said. "It's a highly significant finding. And it's worrisome enough to definitely look into. I think the CDC people know that."

They also know that some reports estimate the rate of mitochondrial dysfunction in autism to be 20% or more. And the rate among children with the regressive sub-type of autism is likely higher still.

Vaccine safety officials on the March 11 call may have been open to discussing mitochondria and autism, but they were probably highly unprepared for what was to come next.

One doctor reported his findings from a five-year study of children with autism, who also showed clinical markers for impaired cellular energy, due to mild dysfunction of their mitochondria.

The biochemistry of 30 children was studied intensively, and in each case, the results showed the same abnormalities as those found in Hannah Poling, participants said. Each child had moderate elevations or imbalances in the exact same amino acids and liver enzymes as Hannah Poling.

All thirty children also displayed normal, healthy development until about 18-24 months of age, when they quickly regressed into clinically diagnosed autism (and not merely "features of autism"), following some type of unusual trigger, or stress, placed on their immune system.

Researchers explained on the call that some data show that mitochondrial dysfunction can convert into autism "in numbers that make it not a rare occurrence," one participant told me. They explained this as "a distinct syndrome; not a mixed bag at all. Every kid had mild mitochondria dysfunction and autistic regression."

Another surprise came when one researcher announced an "inheritance pattern" that linked each case through the genetics of the father: In families where two cousins had autism, the genetic link was always through the father.

This unexpected discovery would clearly implicate nuclear DNA inheritance, and not mitochondrial DNA, which is inherited only through the mother.

Gerberding and others had previously insisted that Hannah and her mother, Teri Poling, both had the same single point mutation in their mitochondrial DNA. CDC officials asserted that Hannah had a pre-existing disease, a rare genetic glitch in her mitochondria, that may well have manifested as "features of autism" on its own, perhaps even without an environmental trigger.

"It's not in the mitochondrial DNA, and it's not rare," one participant confirmed. In fact, he said, many people probably carry the nuclear DNA mutation that confers susceptibility to mitochondrial dysfunction, they just don't know it.

1-in-50 GENETIC RISK?

On the call, speculation on the prevalence of a genetic mutation that could confer mild mitochondrial dysfunction in the general population ranged from about 1-in-400, to a staggering 1-in-50, or 2% of all Americans.

There was talk about the urgent need to do mapping studies, and find the locus of this gene. Some of the researchers said they want to test all 30 children for the actual DNA mutation. There was some expectation that they might discover that the mutation goes back generations, so parents and grandparents might be tested as well.

One belief is that a particular mutated gene may have become prevalent over the centuries, because of selective advantage. Mild mitochondrial dysfunction reportedly has been associated with intelligence, because it can increase activity of the brain's NMDA receptors. A large number of receptors can produce increased intelligence, but it can also increase risk of brain disease, one doctor explained to me. It's possible that increased receptor activity acts in same way.

But not everyone agrees that mitochondrial dysfunction is a purely inherited affair. Some researchers believe that, while a susceptibility gene for mitochondrial problems certainly exists, some type of environmental trigger, or "adversity," as one doctor put it, is needed to turn the mutation into a dysfunction.

The medical literature is replete with studies on mitochondrial health and the adverse impact of mercury, aluminum and other toxins. Even AIDS drugs like AZT and prenatal alcohol consumption can damage mitochondria and impact cellular energy.

The mercury-containing vaccine preservative, thimerosal, for example, "can definitely kill cells in vitro through the mitochondria," one teleconference participant told me. "And some people are beginning to suspect that the dose of hepatitis B vaccine given at birth might be interfering with proper mitochondrial function in certain children."

While the cause of mitochondrial dysfunction is up for the debate, so too is its potential effect on regressive autism.

All the researchers I spoke with agreed that, in many cases, there was an underlying, asymptomatic mitochondrial dysfunction, aggravated by some other stressful event imposed on the child's immune system, resulting in autism.

Such "metabolic decomposition" occurs when a child's system simply "cannot meet the energy demand needed to fight the stress of illness," one doctor explained.

But what causes the stress? That is a very big question.

Apparently, in only two of the 30 cases, or 6%, could the regression be traced directly and temporally to immunizations, and one of them was Hannah Poling. In the other cases, there was reportedly some type of documented, fever-inducing viral infection that occurred within seven days of the onset of brain injury symptoms.

All 30 of the regressions occurred between one and two years of age, at a time when the still-developing brain is particularly vulnerable to injury.

But if a significant minority of autism cases was caused by mitochondrial dysfunction aggravated by common childhood illnesses, then shouldn't we see fewer cases today than, say, at the beginning of the 20th Century? And wouldn't developing countries likewise show far more prevalence of autism than the United States?

Not necessarily, some experts said. They noted that many viral infections are still quite prevalent in modern-day America, and many children still get these types of viral infections about once a month, on average.

If that is the case, then why doesn't every child with "mito" dysfunction regress into autism? Surely, they must encounter viral infections during their yearlong window of neurological peril.

Again, not necessarily: Some doctors said it would depend on the severity of the dysfunction, the type of virus encountered, and perhaps other factors that are still not understood.

But at least two of the 30 kids with mito deficiencies were pushed over the edge into autism by their vaccines, and some researchers feel the number is probably much higher than that in the larger population.

"Vaccines, in some cases, can cause an unusually heightened immune reaction, fever, and even mild illness," one participant said. "A normal vaccine reaction in most kids would be very different in a kid with a metabolic disorder. We know it happened to at least two kids in this study, and I'm certain there are many more Hannahs out there."

One theory currently in circulation about what happened to Hannah and other children like her, is an apparent "triple domino effect." According to this hypothesis, it takes three steps and two triggers to get to some types of autism, and it goes like this:

STEP ONE: Child is conceived and born healthy, but with an underlying nuclear DNA genetic susceptibility to mitochondrial dysfunction, inherited from dad.

TRIGGER ONE: An early environmental "adversity" occurs in the womb or during the neonatal period, perhaps caused by prenatal exposure to heavy metals, pollutants, pesticides and medicines. Or, it occurs in early infancy, through environmental toxins, thimerosal exposure, or even the Hepatitis B vaccine "birth dose." This trigger results in:

STEP TWO: Child develops mild, usually asymptomatic mitochondrial dysfunction (though I wonder if the ear infections and eczema so common in these cases might also be symptoms of mito problems).

TRIGGER TWO: Child, now with an underlying mitochondrial dysfunction, suffers over-stimulation of the immune system beyond the capacity of his or her metabolic reserves. This stress is either via a viral febrile infection, or from multiple vaccinations, as in the Poling case. This trigger results in:

STEP THREE: Acute illness, seizures, encephalopathy, developmental regression, autism.

Such a scenario might help explain why autism has increased right along with the addition of more vaccines to the national schedule.

And it might help explain why autism rates are not plummeting now that thimerosal levels have been significantly reduced in most childhood vaccines.

It's possible that exposures from the flu shot, and residual mercury left over in other vaccines -- perhaps in synergistic effect with aluminum used as an "adjuvant" to boost the immune response - might "contribute to the toxic mix that causes childhood mitochondrial dysfunction in the first place," one of the doctors said.

But like many hypotheses, this one has competition. Some researchers believe that the modern American diet is largely to blame for an increase in the number of children whose underlying mitochondrial dysfunction is "triggered" into autism by febrile infections.

The answer, they hypothesize, is corn.

The American diet has become extraordinarily dependent on corn oil and corn syrup used in processing, these experts contend. They say that corn oil and syrup are inflammatory, whereas fish oil is anti-inflammatory. Could our diet be a factor in making this mutated gene become more pathogenic? It's a biochemical defect that leads to biochemical disease, supporters of this theory say: The gene itself becomes more of a problem.

WHAT NOW?

This information raises so many questions it makes your head swim.

First and foremost among them: What to do about vaccinating children with known mitochondrial dysfunction?

In many respects, these kids should be first in line for vaccination, to prevent some illnesses that might trigger an autistic regression during the window of vulnerability. On the other hand, with multiple vaccinations, such as the case with Hannah, there is also a risk of overtaxing the immune system, and likewise triggering regression into autism.

What's needed most urgently, if possible, is a quick, affordable and efficient method of testing children for low cellular energy, perhaps before vaccination even begins.

There was some discussion on the conference call about altering the vaccine schedule in some way, to lower the risk of immune over-stimulation in susceptible children. Certainly, pressure will grow for a change in the schedule - the question is how, when, and if such changes will be made.

Some of the suggestions may not be popular among public health officials. They include:

1) Establishing a maximum number of vaccine antigens to which any child could be exposed on any given day.

2) Permitting the option of separating out the measles-mumps-rubella (MMR) live virus combination vaccines into three distinct "monovalent" shots.

3) Not giving the varicella vaccine (chicken pox) on the same day as the MMR injection - the CDC recently withdrew is recommendation for the Pro-Quad MMR+Varicella vaccine because it doubled the risk of seizures.

Another option is to create new "recommendations for administering multiple vaccines to children who have fallen behind in the recommended childhood immunization schedule," according to the website of the Institute for Vaccine Safety at Johns Hopkins Bloomberg School of Public Health.

Hannah had missed some shots and her doctor decided to "catch up" with the schedule by administering five shots, containing nine vaccine antigens, at once. But some autism activists have pointed out that giving five shots in one day is not that uncommon.

Moreover, they claim, many children regressed into autism following normal vaccination, when the parents religiously adhered to the official schedule.

According to the Johns Hopkins site, "Additional research is needed to determine if other children with autism, especially those with 'the regressive form' of autism, have the same or similar underlying mitochondrial dysfunction disorders."

It adds that, "the advisory groups who make recommendations regarding vaccines will undoubtedly examine this case carefully and make decisions regarding the potential need for changes."

That day may come sooner than you think. It was just announced that, on April 11 in Washington, DC, the National Vaccine Program Office at HHS will convene a meeting of the National Vaccine Advisory Committee's Vaccine Safety Working Group. The Working Group was established to go over the CDC's Immunization Safety Office draft research agenda, and to, "review the current vaccine safety system."

The meeting is open to the public, and I have my seat reserved. But I honestly don't envy the Working Group's very tricky task at hand.

It remains to be seen how all this plays out. And many important questions still lie ahead.

For example, if mitochondrial dysfunction turns out to be as common as 200-per-10,000, and autism is now at 66 per 10,000, did anything bad happen to any of the other 134-per-10,000 children, apart from autism (i.e., ADD, ADHD, speech delay, etc.)?

Moreover, if 10-20% of autism cases can actually be traced to an underlying mitochondrial dysfunction, then what about the majority of autism cases where this did not come into play?

And, if 20% of autism cases are mito related, and 6% of those cases regressed because of vaccines, that would mean that at least 1% of all autism cases were vaccine related. Some estimates of autism go as high as a million Americans - that would mean 10,000 people with vaccine-triggered autism, and billions of dollars in the cost of lifetime care.

(While we are on the subject, isn't it time to fund a study of vaccinated and unvaccinated children, to settle this debate once and for all?)

Finally, the goals of the CISA Network, (which convened the teleconference) are rather progressive and far reaching. It remains to be seen how well the Network fulfills its stated mission, which includes:

Conduct research into "the role of individual variation" on vaccine injury;

"Empower individuals to make informed immunization decisions;"

Help policy makers "in the recommendation of exclusion criteria for at-risk individuals," and;

"Enhance public confidence in sustaining immunization benefits for all populations"

Let's see how long it takes before Network members hang out the proverbial banner: "Mission Accomplished."

Mito/DNA/Autism/GFCF/Glutamate Thoughts From A Food Process Engineer

Now THIS is the kinda thing I was talking about in my fantasy "Responsible Government" piece. Medical professionals hearing the mito/autism news and applying their understanding from other fields to the autism problem! It even has autism gene theory with, get this, real world application that can be of use for helping kids today!

Except in my fantasy she would not have to be posting this to a CNN site, because NIH would have called her when she sent it into them months ago.

Another fascinating Dr. Gupta comment:

Dr. Gupta,

Here is what I wrote to the NIH in January. It still sums up my thoughts. It should be noted that one of the genes for autism discovered last year codes for a MITICONDRIAL aspartate/glutamate carrier.

I am a former food process engineer who believes, because recent studies have implicated genes which code for glutamate synapses in ASD, we should investigate the effects of both INGESTED and INJECTED excitatory free amino acids (glutamic acid and aspartic acid) on children with these autism genes.

If excitatory free amino acids affect ASD children, it would explain both the impact of GF-CF diets AND a vaccine link. Vaccines have free glutamic acid added to preserve the virus. I have created and attached a chart showing where free glutamic acid comes from. It is found in extremely high amounts in processed wheat and dairy products so much so that food manufacturers use these two items routinely to produce free glutamic acid in foods but with a clean label.

Consequently, a child may not improve on a GF-CF diet alone, because it doesn’t limit all potential sources of free glutamic acid like soy. Children are tested at birth for PKU and phenylalanine is limited until the brain is hardwired by the age of 7. Why not treat the predisposition for autism similarly and limit the glutamic and aspartic amino acids in the diets of children with autism genes?

ASD also includes errors of metabolism for sulfur containing amino acids like cysteine. Cysteine is converted to taurine and glutathione by the liver. Taurine regulates heartbeat and osmotic balance as well as bile production and was found to be low after a seizure. In ASD, symptoms include arrhythmias, digestive disorders and a high rate of epilepsy, suggesting that taurine production may be compromised. Glutathione levels are also lower in ASD leading one to conclude that possibly, cysteine metabolism may be responsible for the myriad and seemingly unrelated additional symptoms of ASD. It should be noted that glutamate interferes with the handling of cysteine. When cysteine metabolism is compromised, homocysteine levels may increase. The lower levels of glutathione may put ASD individuals at risk of mercury poisoning, since glutathione helps eliminates mercury from the body.

It should be noted that the NMDA receptors that respond to both glutamate and aspartate are found in the amygdala - part of the limbic system involved in the perception of taste and smell as well as fear. Activating the amygdala in ASD, causes gaze avoidance. ASD children may also over-react to smells and tastes and face to face encounters can overwhelm them with fear. Limiting excitatory amino acids that target the amygdala may help.

Japan consumes more MSG, and fish (a dietary source of mercury) than nearly any other country. Compared to the amount of mercury consumed in fish and the amount of MSG consumed in the diet, the MMR contribution was probably small compared to a typical Japanese diet. In Japan, the MMR vaccine was stopped in 1993. Autism rates still increased. Perhaps in Japan, the diet plays more of a role in autism than the vaccines. Children from other countries with a lower consumption of fish and MSG may find a stronger correlation between vaccines and autism.

New research studies into ASD should include people who are sensitive to the food additives MSG and aspartame. MSG-sensitive persons have reported a distinct lessening of symptoms by using taurine, ibuprofen, CoQ10, Vitamins B6 and B12, carbohydrate, foods high in butyric acid like butter, and Magnesium. Perhaps they share some of the same genes that predispose a child to ASD. New treatment studies should look into these easily available, inexpensive and relatively safe compounds.

Based on what I have observed, here are my recommendations:

1. Treatment of ASD?

REMOVAL of excitatory amino acids (glutamate, aspartate) from VACCINES.
Glutamate and aspartate restricted diet (similar to treatment for PKU) in addition to GF/CF diet.

Supplementation of taurine, glutathione, vitamins B6, C, magnesium, CoQ10.
Increased carbohydrate.

Labeling of free glutamic and aspartic acid on food labels.
Glutamate blockers, anti-histamines and leukotriene blockers for children already suffering or getting vaccinated.

We should calm their surroundings, encourage quiet tasks and less-threatening contact to enhance communication. We need to give them space and not overwhelm them.


2. Diagnosis of ASD?

Test for autism genes preferably AT BIRTH like PKU.

Tests for aspartic acid, glutamic acid, glutathione, taurine, cysteine, homocysteine.


3. Risk factors for ASD?
Autism Genes
Sensitivity to excitatory amino acids
Low taurine, Low glutathione
Sulfite Sensitivity
Vaccination with glutamic acid as a preservative
Damage to the microglia
Overactive immune system
Junk food diet
Aspartame in medications or vitamins or foods
Multiple food allergy


4. Biology of ASD?

Excess CNS sensitivity,

Inability to handle sulfur-containing amino acids,

Overactive immune response linked to Nerve Growth Factor


5. Other areas of ASD research?

Common genes in Alzheimer’s, Parkinsons, ALS, MS, and excitatory amino acid sensitivity.

Study persons without ASD who suffer from overactive CNS or neurodegenerative disease and sensitivity to excitatory amino acids. See if they share same genes.

Could Alzhemier’s sufferers simply be ADS children whose brains were hard-wired before damage by the environment?


Thank you for this opportunity to share my ideas on this very important topic,

Please see this webpage that clearly shows why a wheat and dairy based processed food diet may be very harmful to a child sensitive to excitatory amino acids:
http://www.msgtruth.org/avoid.htm

HT:Here in HP

Dr. Poling Responds To Autism/Vaccine Nay Sayers

Dr. Stephen Novella on his blog NeuroLogica has posted his evaluation of the Poling case and why he believes it does not support the vaccine autism connection.

Dr. Jon Poling has responded as seen on The Age of Autism countering the arguement and expanding on the information that has been available publicly on the case.

It is a discussion between two neurologists and I will need to read them each 5 times before I can even begin to comment on the conversation.

But I will note two things.

First, I am impressed that Dr. Poling lists his potential conflicts of interest at the end of his letter. I think that every medical professional should do that as a part of their signature (For example I would sign Ginger Taylor, B.S., M.S., Mother of regressive autistic child who suspects vaccines had a causal relationship to ASD, Has Google Ads on her autism blog).

Second, for all of his in depth analysis of the medical facts in this case, Dr. Novella failed to correctly discern the sex of the child in question. He refers to Hannah several times as "he" and "the child", never as a female. He criticizes David Kirby's articles about the case, but did not read them thoughtfully enough to see that Mr. Kirby was clearly talking about a girl.

I will reserve this space for further comment as I come to understand this case further.

I will post both pieces:

Has the Government Conceded Vaccines Cause Autism?
Published by Steven Novella

No. But David Kirby and other anti-vaccinationist ideologues and members of the so-called mercury militia would like you to think so. For background, the Autism Omnibus refers to a set of hearings before the Vaccine Injury Compensation Program regarding claims by about 5000 parents that their childrens’ autism was caused by vaccines. These claims are primarily based upon the various hypotheses that the MMR vaccine, or thimerosal in some vaccines (but not MMR), or the combination of both, is a cause of autism.

So far there have been hearings, but only one final decision. In November the US government settled one case in favor of the petitioner. This is the case those who have supported the failed hypothesis that vaccines cause autism now point to as admission that they were right all along (or at least as a means of stoking the flames of fear about vaccines.) But the US government did not admit vaccines cause autism - they conceded one case that is highly complex and not necessarily representative of any other case and cannot be reasonably used to support the vaccine/autism connection.

David Kirby, author of Evidence of Harm, wrote a highly misleading article the other day in the Huffington Post on this issue. Orac has already done an excellent job of tearing down Kirby’s claims. He points out that legal cases are often decided for legal - not necessarily scientific - reasons. That the government only conceded that “compensation is appropriate.” That is all - they conceded nothing about the larger question of vaccines and autism. Orac also points out that if this case were a concession of a connection why would the petitioner’s lawyers settle and give away a case that could win them all their other cases?

David Kirby has also written a follow up article, where he publishes verbatim the US government’s decision. Kirby asks his readers:

If you feel this document suggests that some kind of link may be possible, you might consider forwarding it to your elected representatives for further investigation.

But, of course, if you feel that this document in no way implicates vaccines, then let’s just keep going about our business as usual and not pay any attention to all those sick kids behind the curtain.

I think Kirby is hoping that most people will not have the patience or medical background to read and understand the entire document, and that they will come away with a vague notion that there must be something to all this vaccine fear-mongering. What does the document really tell us?

To summarize the case history, the child in the case appeared normal and healthy, except for chronic otitis media, until about 20 months of age at which time he had a series of vaccines according to the routine vaccination schedule. Two days later the child had a fever to 102.3, was lethargic, irritable, and would arch his back when he cried. The child then developed a rash. It was later determined that the child had: “encephalopathy progressed to persistent loss of previously acquired language, eye contact, and relatedness.” The child regressed and developed symptoms similar to those of autism spectrum disorder. However, the child does not have autism - he has a regressive neurological disorder that includes blood and muscle abnormalities not seen in autism, and any clinical resemblance to autism is not a reflection of a common cause.

Six years after symptoms began the child also developed partial temporal lobe epilepsy that required treatment.

During this time the child also had an extensive workup, which discovered:

A CSF organic acids test, on January 8, 2002, displayed an increased lactate to pyruvate ratio of 28,1 which can be seen in disorders of mitochondrial oxidative phosphorylation.

A muscle biopsy test for oxidative phosphorylation disease revealed abnormal results for Type One and Three.

In February 2004, a mitochondrial DNA (”mtDNA”) point mutation analysis revealed a single nucleotide change in the 16S ribosomal RNA gene (T2387C)

It if often difficult or impossible to draw firm conclusions from a single case, so I will lay out what I see as all the possible alternative hypotheses to explain this information.

1) One possibility is that the child was perfectly normal prior to the vaccines, which caused an encephalitis (inflammation of the brain) which caused brain damage, including the later seizures. The metabolic disorder and mutation may be a red herring and have no bearing on the child’s clinical condition.

2) The mitochondrial disorder predisposed the child to have a reaction from the vaccines, resulting in encephalitis. The subsequent neurological regression was due to some combination of the vaccine-induced encephalitis and the underlying mitochondrial disorder.

3) The child’s mitochondrial mutation is the primary cause of their neurological regression, but that this regression was exacerbated by the vaccine-induced encephalitis (this seems to be the US government’s conclusion).

4) The child has a mitochondrial encephalopathy which is the sole cause of all of the child’s neurological signs and symptoms. The reaction to the vaccines may have played no role at all in the subsequent regression, and the child’s current neurological condition is exactly what it would have been had they never been vaccinated. It is even possible that the encephalitis was merely the first manifestation of the mitochondrial disorder and the timing after the vaccines was merely coincidental.

That lays out the spectrum of possibilities in this case. At this point in time we do not have (or at least I am not privy to) sufficient scientific information to say definitively where along this spectrum the truth lies. The US government’s decision was based partly on this uncertainty - erring on the side of compensating the child and family.

But we can discuss the plausibility of each scenario. Kirby dismisses anything resembling option 4, but his dismissal is naive and unjustified. In fact the patient’s clinical syndrome resembles what is called a mitochondrial encephalopathy - with increased lactic acid, abnormal muscle biopsy, neurological regression, appropriate age of onset, even seizures. It is probably not a coincidence that the child has a point mutation in a gene that has been previously linked to these very mitochondrial disorders. Kirby incorrectly argues:

While it’s true that some inherited forms of Mt disease can manifest as developmental delays, (and even ASD in the form of Rhett Syndrome) these forms are linked to identified genetic mutations, of which T2387C is not involved. In fact little, if anything, is known about the function of this particular gene.

This is misleading. Kirby refers to “this particular gene” which makes me think that he believes T2387C is a gene. It’s not - it describes a point mutation (at location 2387 a thymidine has replaced a cytosine). The gene is the 16S ribosomal RNA gene. Mutations in this gene have been identified to cause mitochondrial encephalopathy. So Kirby is just wrong. It is true that I could not find that this specific mutation has been identified before, but that is common in genetics - a disease is linked to point mutations in a specific gene (or perhaps specific regions of a gene) but most or all families identified have their own specific mutation.

This makes option 4 very plausible - it would be an incredible coincidence if this child just happened to have a mutation in a gene that was known to cause their exact constellation of neurological signs and symptoms and yet the mutation was not the sole or primary cause of those symptoms.

But it does not rule out option 3 - that the mitochondrial disorder was the primary cause of the child’s neurological disorder but that a reaction to the vaccines worsened the ultimate symptoms. Therefore the government’s decision was reasonable - but is absolutely not a concession about any claim made by the petitioners concerning a link between vaccines an autism.

It does, however, make any hypothesis resembling option 1 or 2 extremely unlikely. Further testing regarding the physiological effects of this child’s specific mutation would be helpful, and such testing may be under way but I could find nothing published to date. It is theoretically possible that the identified mutation does not cause a change in the gene product or mitochondrial function, and is therefore just a coincidence. But this is unlikely given the clinical features in this case are a good match to known mutations of that gene.

Kirby, however, apparently wants to wring as much fear and confusion out of these events as he possibly can. So now he speculates wildly that maybe children diagnosed with autism really have this mitochondrial disorder combined with vaccines (he has to keep vaccines in the loop). Given the rarity of such mutations, and the fact that there were specific features in this case that would likely be uncovered in the routine evaluation of a child with autism (like an elevated lactic acid), it is highly unlikely that there are many children with vaccine-triggered mitochondrial encephalopathy mimicking autism out there.

It has been found that some children with autism have mitochondrial dysfunction - one study found that 7.2% of subjects with autism had “definite mitochondrial respiratory chain disorder.” Poling et al, in response to this child’s case, did a retrospective study of children with autism and with other neurological disorders and found that “Aspartate aminotransferase was elevated in 38% of patients with autism compared with 15% of controls.” Such findings are preliminary - the only conclusions that can be drawn is that the association between autism and metabolic disorders requires further investigation. However, these studies did not look at the incidence of suspicious mitochondial mutations in autism, and these findings may not be relevant to this case.

Kirby also wildly speculates that perhaps the evil toxins in vaccines caused the mutation in the first place. He writes:

Use of the AIDS drug AZT, for example, can cause Mt disorders by deleting large segments of mitochondrial DNA. If that is the case, might other exposures to drugs or toxins (i.e., thimerosal, mercury in fish, air pollution, pesticides, live viruses) also cause sporadic Mt disease in certain subsets of children, through similar genotoxic mechanisms?

Among stiff competition, this is perhaps the most absurd and scientifically ignorant thing Kirby has every written. AZT does NOT cause a genetic disorder. AZT blocks DNA replication (it blocks the copying of DNA) - that is its mechanism as an anti-retroviral drug. In patients it can also block mitochondrial DNA replication, thereby causing mitochondrial depletion. This results in there being too few mitochondria (the energy factories of cells) in some cell populations and causes dysfunction in tissue that is especially susceptible to the effects of this dearth of mitochondria. This is a side effect of AZT and also other retrovirals because of sustained use at doses designed to inhibit DNA replication. This does result in some effects that are similar to mitochondrial genetic disorders - because both result in insufficient mitochondrial activity. But that is the only similarity. AZT does not cause a disseminated somatic mutation, which is the incredible analogy that Kirby is making.

What Kirby is suggesting is that in infants and toddlers toxins can cause the same point mutation in millions of different cells throughout the body. Toxin-induced mutations do not cause genetic diseases, unless they occur in a germ cell in which case a mother or father can pass the mutation onto their children. If it occurs in the womb then large cell populations may be affected (whatever cells derive from the cell that had the mutation). But in a child a point mutation would affect only one cell and any cells that derive from it. A toxic mutagen would cause different random point mutations in different cells. This could not cause the mitrochondrial encephalopathy in this child. It can increase the risk of cancer, because cancer can develop from a single mutation in a single cell that causes it to become neoplastic.

Conclusion

This is a unique and idiosyncratic case that raises more questions than it answers. In my opinion as a neurologist, with the information provided, the child has a mitochondrial encephalopathy. The role of the vaccines is unclear, but at worst a rare vaccine reaction exacerbated the underlying mitochondrial disorder. This case has no clear implication for the larger question concerning vaccines and autism, which is likely why both sides agreed to settle.

Yet those who insist, despite the evidence, on claiming that vaccines or mercury are linked to autism are likely to add this permanently to their litany of misinformation and fear-mongering.

Note: I am searching for any follow up information pertinent to this case and will post any addendum here.

DR. JON POLING TO DR. STEVEN NOVELLA ON AGE OF AUTISM

PolingsBy Dr. Jon Poling, father of Hannah Poling.

OPEN LETTER TO DR. STEVEN NOVELLA
IN RESPONSE TO "Has the Government Conceded Vaccines Cause Autism?"

Dr. Novella,

Thank you for generating interesting discussion regarding my little girl, Hannah Poling. I would like to give you additional information in order to generate further productive discussions on this matter amongst the neurology community. This information should assist you, Dr. DiMauro, and Dr. Trevethan, who have also commented publicly, to formulate better theories as to the significance of Hannah’s mitochondrial dysfunction in relation to her autism.

1. Mito Dysfunction or Mito Disease? Chicken or Egg?

To begin with, I would like to point out that the spectrum of mitochondrial dysfunction is probably considered more broad and complex than the spectrum of neurobehavioral abnormalities seen with autism. Dysfunction of the mitochondria, specifically dysfunction of the oxidative phosphorylation pathway, most likely contributes, but may not be the cause of many diseases—including Parkinson’s disease, Friedreich’s Ataxia, Alzheimer disease, etc. Thus, it is probably incorrect to refer to mitochondrial dysfunctional and mitochondrial disease interchangeably. Indeed, the role of the dysfunctional mitochondrial are yet to be clarified in these diseases. Thus, I will refer to Hannah’s metabolic condition as a mitochondrial dysfunction, not a mitochondrial disease.

2. Mito Genetic Finding? Mito mtDNA ‘red herring’ ?

ADDITIONAL GENETIC TESTING NOT AVAILABLE IN THE J CHILD NEUROL CASE REPORT: 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. It is unlikely, but possible, that the mutation is significant to Hannah, but in such a case, it must work in concert with other nuclear genes to cause her mitochondrial dysfunction. To our knowledge, this point mutation has not been reported in cases similar to Hannah’s.

3. Encephalitis? Metabolic Encephalopathy? Or “Regressive Encephalopathy with Features of Autism Spectrum Disorder”

The other interesting term you used was encephalitis rather than encephalopathy. We are not sure that she had an “-itis” but we did clearly document a regressive encephalopathy based on not only our parental reporting, but also based on the pediatrician’s documents, affidavits from other family members, and the growth curve measurements (injury pattern). Early on in the regression we did note back arching (opisthotonus), fever, and disrupted sleep. Although fever occurred a lumbar puncture was not performed.

An interesting developing story in autism research is the immune/inflammatory connection. In her senior resident thesis, Dr. Anne Comi, a former JHU colleague, along with Dr. Andy Zimmerman, reported, the increased prevalence of autoimmune disease in families of autistic offspring. Interesting, Hannah also has a maternal family history of autoimmune disease. Dr. Carlos Pardo, another one of my former chief residents, along with Andy and Dr. Vargas, published a beautiful study in the Archives of Neurology, demonstrating neuroinflammation on autopsy of brain samples and inflammation cytokine markers in the CSF of individuals with Autism. The interesting thing was that inflammation was demonstrated in autopsy specimens from adults as old as 44 years of age. The conclusion was that further research would be required to determine if inflammation was a primary disorder in autism or; alternatively, if inflammation and microglial activation was secondary to neurodegeneration. Dr. Sudhir Gupta at UC Irvine has a nice model of how the two pathways of neuroinflammation and mito dysfunction may not be mutually exclusive. This remains to be seen; however, study of mitochondrial dysfunction and neuroinflammation hold the promise of treatment development. The two avenues of research deserve funding at the highest levels.

4. How many Hannah Polings are out there?

The short answer is that nobody knows. However, there is emerging data to suggest that she is not alone.

Dr. Shoffner will be presenting his experience with 37 patients with combined autism and mitochondrial dysfunction at the AAN meeting in Chicago this April. 65% of his referrals are positive for mitochondrial dysfunction. Of course, his yield is subject to referral bias as a mito expert, so the prevalence of mitochondrial dysfunction in Autism is surely less than 65%.

The best estimate to date of the prevalence of mitochondrial dysfunction in autistic patients comes from Oliviera et al. in a population of 120, 5 of 69 (or 7.2%) showed mitochondrial dysfunction. If this is generalized to the US estimate of 1 million patients with ASDs, then the number of kids like Hannah could be 72,000! Isn’t this worth further study?

Dr. Shoffner furthermore advocates, along with us, that vaccination is important even for kids with mitochondrial dysfunction. I would argue that you should not give nine at one time and that none of them should contain Thimerosal (mercury).

5. Thimerosal—On or Off the Table?

I don’t want to dwell on mercury, as this theory is not why HHS conceded Hannah’s case (imo). Dr. DiContanzo just wrote an interesting blog about how his opinion of mercury in vaccines has changed (http://drugs.about.com/b/2008/03/08/mercury-in-vaccines-and-autism-the-burden-of-proof-may-shift.htm).

My opinion is that mercury is a potent neurotoxin. Therefore, don’t inject it into kids! Interestingly, basic research studies have shown that Thimerosal toxicity occurs through mitochondrial pathways. Officials point to the large epidemiology studies as proof that there is no link between thimerosal and autism. However, these studies are not powered to disprove the null hypothesis when considering that the mitochondrial autistic population may be just a small percent of the case totals. Remember that while the CDC sponsored Verstraten study is hyped as a negative study, it DID find a statistically significant increase in childhood tics in those exposed to higher doses of thimerosal.

6. Hannah was destined to regress? Or was she?

Some experts have already stated that ‘mitochondrial disease’ is degenerative so the vaccine reaction was just the start of an inevitable decline. This was neither the opinion of Dr. Richard Kelley at KKI nor Dr. John Shoffner. In fact, the markers that led us down the mitochondrial trail (inc AST but not ALT, low serum bicarbonate, and slight increased CK, increase in the alanine to lysine ratio on PAA) are no longer present. Furthermore, in our pilot study (unpublished but mentioned in the J child neurol paper), Dr. Frye (the statistician for our study and also a child neurologist) found a non-significant trend that AST decreased toward normal with increasing age. With further studies we hoped to examine the hypothesis that this abnormality may be representative of a developing/immature biochemical pathway present in some children.

7. Triple Hit Hypothesis—#1Underlying genetic susceptibility #2Insult must occur during specific developmental period #3 A certain vaccination or combination thereof is the environmental trigger (?vaccine component like thimerosal ?direct immune stim/fever reaction ?live virus reaction?)

The implication is that Hannah’s type of autism requires a genetic susceptibility and properly timed insult to manifest disease. We have not subjected Hannah to another muscle biopsy or re-examined ox phos functional assays that were published in the paper. I can inform your readers though that the serum biochemical markers have resolved, growth resumed and continues along a normal trajectory, and there have been no other episodes of regression since 2000. We are however left with autism and later in 2006, epilepsy.
It is recommended that studies be initiated immediately to screen siblings of cases to identify biochemical markers so as to identify potential screening tests.

I agree with the mainstream that my daughter’s case has raised many intelligent discussions and questions. I’m very proud of her for starting this discussion. Our hope is that further research into this case and others like it, we will be also to find screening tests to prevent what happened to my daughter from happening to anybody else.

(Dr. Poling acknowledges the editorial comments and insightful suggestions of Dr. Richard E. Frye. He also would like to declare his conflicts of interest. First of all, he is the father of Hannah Poling. Dr. Poling has also accepted consultancy or speakers honoraria from Pfizer, Eisai, Ortho-McNeil, Biogen, Teva, Immunex (now Amgen), and Allergan.)

PS While I thought it useful to clarify some of the neurological issues raised by the government's concession of my daughter's case, please understand that I will not be able to respond to individual comments posted. Thank-you. Jon