New Findings on Genetic Link Between Autism and Mitochondrial Disease
Researchers at Medical Neurogenetics have found that there may be a genetic link between autism and mitochondrial disease, “a muscle-weakening disorder,” today’s Reuters reports. Dr. John Shoffner, a neurologist and geneticist and one of the owners of the Atlanta-based company, reported at the American Academy of Neurology meeting in Chicago that 37 autistic children were evaluated for mitochondrial disease at his clinic. More than 60 percent of them (24 of the children, or 65 percent) were found to have mitochondrial defects based on evaluating genetic samples and clinical information. Dr. Shoffner noted that the clinic’s findings need to be confirmed by other studies.
More from Reuters:
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……….
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.
According to its website, Medical Neurogenetics “provides Molecular and Metabolic genetic testing and consultation for a variety of inherited disorders affecting children and adults.” Dr. Shoffner identified the mitochondrial disorder in Hannah Poling and is the co-author of a paper on Developmental Regression and Mitochondrial Dysfunction in a Child With Autism by Hannah’s father, Dr. Jon Poling.
Tags: asd, asperger, autism, genetics mitochondrial disease, government, mercury, Parenting, pdd-nos, vaccine court, VaccinesRelated Stories
POSTED IN: Genetics, Health, Neuroscience
18 opinions for New Findings on Genetic Link Between Autism and Mitochondrial Disease
Mike
Apr 13, 2008 at 5:59 pm
I love the way the medical establishment is reverse engineering this disorder to draw attention away from the environmental culprits. Here are some interesting facts about Mitochondrial Disease:
What causes mitochondrial disease?
….. An uncertain percentage of patients acquire symptoms due to other factors, including mitochondrial toxins.
What are these toxins? 100-1 says Mercury or another one of the toxins in vaccine’s is on the list.
How are mitochondrial diseases treated?
There are no cures for mitochondrial diseases, but treatment can help reduce symptoms, or delay or prevent the progression of the disease.
Treatment is individualized for each patient, as doctors specializing in metabolic diseases have found that every child and adult is “biochemically different.” That means that no two people will respond to a particular treatment in a specific way, even if they have the same disease.
* Certain vitamin and enzyme therapies, along with occupational and physical therapy, might be helpful for some patients.
Vitamins and supplements prescribed might include:
- Coenzyme Q10
- B complex vitamins: thiamine (B1), riboflavin (B2), niacin (B3), B6, folate, B12, biotin, pantothenic acid
- Vitamin E, lipoic acid, selinium, and other antioxidants
- L-carnitine (Carnitor®)
- Intercurrent illness supplement: vitamin C, biotin
* Diet therapy, as prescribed by your doctor along with a registered dietitian, might be recommended.
* Antioxidant treatments as protective substances are currently being investigated as another potential treatment method.
HMMM, treating it without man-made drugs, berry interesting! Sounds like my approach to helping kids with Austims (detox-supplement-diet) may also help people with M-D.
I’m very confident more research funded by the drug companies (drug companies fund AMD, all medical studies) will find that Autism is caused by other genetic culprits, but I’m also 100% certain that those genetic defects are influenced by environmental toxins like Mercury. In my opinion of course, I’m not a doctor nor do I play on on TV. (on the web, sometimes, lol)
María Luján
Apr 13, 2008 at 6:45 pm
From a Doctor in the UMDF
“Sporadic Cases — Where There Are No Affected Relatives
In the “real world”, in the majority (perhaps about 75%) of cases the patient is the only family member affected with mitochondrial disease. These cases are called “sporadic”, and present much difficulty in answering the questions posed about regarding inheritance.
The first question is whether the problem is due to genetics, environment, or some combination of the two. Certainly, the genetic aspects of mitochondrial disease are well known and were briefly summarized above. However, not all mitochondrial disease is primarily genetic. For example, anti-retroviral medications used to treat HIV/AIDS can damage mitochondria and cause symptoms due to resultant energy failure. Removal of these drugs reverses the process and the symptoms resolve. There are other environmental causes of mitochondrial disease, and likely many that we do not know about.
In the opinion of this author, most mitochondrial diseases are probably both genetic AND environmental in origin. Even in the case of anti-retroviral medications, thousands of individuals have no problem on these drugs while only a handful do. Likely, there are genetic reasons for the high susceptibility to these drugs in an unlucky few - a genetic predisposition of an “environmental” disease. On the other hand, in MELAS, which clearly is primarily genetic in origin, neurological deterioration often occurs during a viral illness and/or fasting - an environmental trigger of a “genetic” disease.
The second question is: If genetic, was the mutation inherited? The answer is usually yes, but not always. New mutations do exist. In particular, deletions (missing areas) of mtDNA tend to be new mutations not present in the mother or siblings. However, deletions with duplications are often inherited, and some duplications are hard to detect.
What this all means is that there are very few answers in most cases where only one person in a family has mitochondrial disease. The condition probably is genetic, and it may or may not be inherited. Either the nuclear or mitochondrial DNA could be involved. Inheritance is probably autosomal recessive, maternal or sporadic (no inheritance), but not necessarily.
Based on many families, some groups give an estimated recurrence risk for mitochondrial disease (chance that each additional child of the same two parents will be somehow affected) of 10-15%. This is probably a reasonable rough estimate, but you should discuss the probability of recurrence for your family with a genetics counselor familiar with mitochondrial disease”.
from
http://www.umdf.org/site/c.dnJEKLNqFoG/b.3042179/
Am J Med Genet B Neuropsychiatr Genet. 2007 Dec
An investigation of mitochondrial haplogroups in autism.
Kent L, Gallagher L, Elliott HR, Mowbray C, Chinnery PF.
Developmental Psychiatry, University of Cambridge, Cambridge, UK.
Family and twin studies provide strong evidence of a major genetic influence in autism, but the underlying gene defects have yet to be characterized. The mothers of boys with autism share autistic traits, raising the possibility of a maternally inherited factor. Mitochondrial DNA (mtDNA) is almost exclusively inherited down the maternal line. We therefore explored the possibility that a particular mtDNA lineage contributes to the risk of developing autism. The mtDNA haplogroup was determined in 162 autism probands, and compared to two sets of population controls. Results show no compelling evidence of an association of any mitochondrial haplogroup in autism
J Child Neurol. 2007 Sep;22(9):1121-3.
Autistic disorder in 2 children with mitochondrial disorders.
Tsao CY, Mendell JR.
Autistic disorder is a heterogeneous disorder. The majority of the cases are idiopathic, and only a small number of the autistic children have associated secondary diagnosis. This article reports 2 children with mitochondrial disorders associated with autistic disorder fulfilling the diagnostic criteria of the American Psychiatric Association Manual of Psychiatric Diseases, 4th edition, and briefly reviews the literature on autistic disorder associated with mitochondrial disorders.
This link
http://jmd.amjpathol.org/cgi/reprint/5/4/197.pdf
points to the discussion of the care and problems with mtDNA confirmation (explained in the link)
Quote:
When a new mutation is found in the mt DNA of a patient with a mitochondrial defect, it is important not to assume pathogenecity until a firm link between the mutation and the cellular dysfunction has been stablished…the mt DNA evolves at a relatively high rate containing many polymorphic sites. Several criteria must be met in the criteria of pathogenecity-
The criteria are
-Presence of heteroplasmy
-Clinical /Biochemical correlations and Family history
-Single Cell PCR
-Cytoplasmic Hibrid (Cybrid ) constructions.
I think that we must wait to know if particular mtDNA mutations are linked to this muscle weakness.
The impact of xenobiotics in mitochondria and newer and better less invasive methods to detect mitochondrial dysfunction are being more and more studied.
Physiol Biochem. 2001 Sep;57(3):267-84.
Laboratory approach to mitochondrial diseases.
Parra D, González A, Mugueta C, Martínez A, Monreal I.
Department of Clinical Biochemistry, Clínica Universitaria de Navarra, Pamplona, Spain.
Dysfunction in mitochondrial processes has been related to several pathologies. In these disorders, the cell suffers oxidative imbalance that is mostly due to defects in pyruvate metabolism, mitochondrial fatty acids oxidation, the citric acid cycle or electron transport by the mitochondrial respiratory chain. These metabolic alterations produce mitochondrial diseases that have been related to inherited syndromes, such as MERRF or MELAS. The main affected organs are brain, skeletal muscle, kidney, heart and liver, because of the high energetic demand and the oxidative metabolism. Moreover, the relationship between mitochondrial dysfunction and neurodegenerative processes, such as Parkinson disease or Alzheimer disease, as well as ageing, has been shown. Because mitochondrias are the target of several xenobiotics, such as aspirin, AZT or alcohol consumption, mitochondrial impairment has also been proposed as a mechanism of toxicity. Most laboratory tests that are available in the diagnosis of mitochondrial illness are assayed in tissue biopsies and are usually difficult to interpret. Recently, it has been shown that non-invasive techniques, such as nuclear magnetic resonance or the 2-keto[1-(13)C]isocaproic acid breath test, may be useful to assess mitochondrial function. This article attempts to show the laboratory approach to mitochondrial diseases, reviewing new techniques that could be of great value in the research of mitochondrial function, such as the 2-keto[1-(13)C]isocaproic breath test
Curr Med Chem. 2005;12(16):1829-39.
Drug-associated mitochondrial toxicity and its detection.
Amacher DE.
Mitochondrial dysfunction is a fundamental mechanism in the pathogenesis of several significant toxicities in mammals, especially those associated with the liver, skeletal and cardiac muscle, and the central nervous system. These changes can also occur as part of the natural aging process and have been linked to cellular mechanisms in several human disease states including Parkinson’s and Alzheimer’s, as well as ischemic perfusion injury and the effects of hyperglycemia in diabetes mellitus. Our knowledge of the effects of xenobiotics on mitochondrial function has expanded to the point that chemical structure and properties can guide the pharmaceutical scientist in anticipating mitochondrial toxicity. Recognition that maintenance of the mitochondrial membrane potential is essential for normal mitochondrial function has resulted in the development of predictive cell-based or isolated mitochondrial assay systems for detecting these effects with new chemical entities. The homeostatic role of some uncoupling proteins, differences in mitochondrial sensitivity to toxicity, and the pivotal role of mitochondrial permeability transition (MPT) as the determinant of apoptotic cell death are factors that underlie the adverse effects of some drugs in mammalian systems. In order to preserve mitochondrial integrity in potential target organs during therapeutic regimens, a basic understanding of mitochondrial function and its monitoring in the drug development program are essential. Toward this end, this review focuses on two topics, (1) the specific effects of xenobiotics on mitochondrial structure and function and (2) a summarization of current methods for quantifying these changes in a preclinical toxicology laboratory.
RAJ
Apr 13, 2008 at 6:53 pm
Mercury is on the list:
http://www.ncbi.nlm.nih.gov/pubmed/17405690?ordinalpos=5&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Here is the relevant sentence in this study:
“Mercury induces mitochondrial dysfunction with reduction in ATP”
María Luján
Apr 13, 2008 at 6:57 pm
Kristina
The mtDNA point mutation that Hannah Poling has is homoplasmic and shared with her mother. From what I understand Dr S. detected the point mutation and the mitochondrial clinical abnormalities-but considering that mother and child share the same mutation, pathogenecity can not be considered in advance- such as the manuscript I posted clarifies.
Dr Poling on the point of point mutation of DNA
http://www.ageofautism.com/2008/03/dr-jon-poling-o.html#more
“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”.
Joseph
Apr 13, 2008 at 7:14 pm
How many in the control group were found to have the same mitochondrial defects?
Daisy
Apr 13, 2008 at 7:59 pm
I can’t help but oversimplify: are they saying that autism is more complex than the vaccine folks would like to think?!
daedalus2u
Apr 13, 2008 at 8:13 pm
“Mitochondrial deficiency can theoretically give rise to any symptom, in any organ or tissue, at any age, and with any mode of inheritance.”
http://www.nature.com/nature/journal/v440/n7084/full/440600a.html
Many things can cause mitochondrial deficiency. Low NO is the one that I am working on. Many of the things that do cause mitochondrial deficiency do so through the low NO mechanism. That is how oxidative stress does it. That is how heavy metals do it. That is how chronic stress does it.
Mitochondrial deficiency is a symptom of HIV, when HAART is used (highly active anti-retroviral therapy). The anti-retroviral therapy inhibits replication of mitochondrial DNA and so prevents the replication of mitochondria.
María Luján
Apr 13, 2008 at 8:52 pm
Joseph, I have the manuscript not available right now. I will check and let you know.
xtiluv
Apr 13, 2008 at 9:19 pm
This is completely off topic, but I thought I would mention that there is a fundraising special on Comedy Central tonight for autism education. It stared at 8pm Eastern Sunday evening. It is nice to see them focusing on education instead of just focusing on research for causation. Also, it’s nice to see people mentioning adults on the spectrum as well. Have a great night everyone!
Kristina Chew, PhD
Apr 13, 2008 at 10:42 pm
Not off-topic—autism is what’s being discussed here—
Kassiane
Apr 14, 2008 at 1:21 am
Adults wont be mentioned on the comedy central thing, it’s for the hate group autism speaks.
(cynical? me? nope. Realistic)
laurentius-rex
Apr 14, 2008 at 3:25 am
Just another subgroup.
What irks me is when people read more into these genetic studies than is contained within them
As I have been saying Autism is not wholly genetic, but there are various (and not identical) genetic routes toward the predisposing factors which in the right admixtures will build into an autistic neurological typology
Caroline Rodgers
Apr 14, 2008 at 8:21 am
To understand why children have non-inherited mitochondrial defects, it is worth digging up a 30-year-old study that found ultrasound can irreversibly damage mitochondria (STEPHENS, R.H., TORBIT, C.A., GROTH, D.G., TAENZER, J.C., & EDMONDS, P.D. (1978) Mitochondrial changes resulting from ultrasound irradiation. In: White, D. & Lyons, E.A. ed.Ultrasound in medicine, New York, Plenum Press, Vol. 4, pp.591-594). Could prenatal ultrasound be causing autism-related mitochondrial disorders?
daedalus2u
Apr 14, 2008 at 11:49 am
Mitochondria turn-over every few months. The only way that a mitochondrial disorder can persist longer than a few months is if there are changes to the regulation of mitochondrial turn-over that persist longer than that. There are no understood mechanisms by which that happens. I think that is the essence of what is happening in CFS and some of the neurodegenerative diseases. It might be happening in autism. It might be happening in Retts. A plausible mechanism would be via low NO. NO is what regulates mitochondria biogenesis, so low NO is going to lead to mitochondrial depletion which then might be perpetuated by ROS production by mitochondria.
Virtually every mitochondria in a person is completely different than every mitochondria that existed a year earlier. That is, the old mitochondria have been replaced with new ones.
The only way a genetic mitochondrial defect can occur is due to damage to DNA either in the nucleus (genomic DNA), or in mitochondria (mtDNA). In both cases that DNA is transferred only from existing cells to daughter cells, that is to cells that result from the division of that existing cell.
If there were an “environmental” cause to DNA damage, that damage would be different in each strand of DNA that was damaged. No two cells would have the same genomic DNA damage, no two mitochondria would have the same mtDNA damage.
If multiple cells, or multiple mitochondria are shown to have the same DNA damage, that damage could only have occurred in the single cell and mitochondria that those multiple cells are descended from.
If every cell in a person has the same DNA damage, that damage could only have occurred when that individual was a single cell, or earlier (i.e. DNA damage in the gametes that formed the single cell).
Widespread identical mtDNA damage in multiple cells is extremely strong evidence (99.99999%+)that there is no involvement of any environmental effect past the first few days of gestation in that mtDNA damage.
Last Week’s Top Posts
Apr 19, 2008 at 1:46 pm
[…] New Findings on Genetic Link Between Autism and Mitochondrial Disease Researchers at Medical Neurogenetics have found that there may be a genetic link between autism and mitochondrial disease, “a muscle-weakening disorder.” […]
Regan
Apr 19, 2008 at 6:35 pm
The clinic somewhat specializes in diagnosis and research in mitochondrial disorders.
It does not state what the overall percentage of children found, even limiting it to this clinic, who do not have autism but do have mitochondrial disease or those who do not have autism nor mitochondrial disease.
It also seems to state that (100%-65%) 35% of the autistic children evaluated for mitochondrial disease at that clinic did not have such. “Disease” did not seem to subtype abnormality, dysfunction or disorder.
Without further elaboration it’s a little like a cardiologist saying that a majority of the patients he sees have heart problems.
“Dr. Shoffner noted that the clinic’s findings need to be confirmed by other studies.”
Absolutely. A less invasive and expensive test would be a good thing, as the relevant genetics, biochemistry and phenotype, not only in relation to autism but in general.
I just think the story implies, perhaps unintentionally, a majority that may or may not be there relative to the general or even autistic population.
It will be interesting to see what the findings are as more work is done.
The Case of Hannah Poling Again
Apr 23, 2008 at 12:20 am
[…] geneticist, and mitochondrial disease expert, agrees with this conclusion: …. In a study of 40 patients with autism—including Poling, he found that two thirds had muscle weakness. If […]
Experts to Hold Meeting on Mitochondrial Disorders
Jun 27, 2008 at 5:55 pm
[…] Jon Poling has asked. Researchers at Medical Neurogenetics have said they have found evidence of a genetic link and mitochondrial disease. Anecdotally, I’ve heard parents of autistic children seeking out tests for mitochondrial […]
Have an opinion? Leave a comment: