Home > Science > More mitochondrial dysfunction than expected?

More mitochondrial dysfunction than expected?

This Science post is by Staff blogger, Leanne Chukoskie, Ph.D.

Like most parents, the Jensens had little information about the factors that might help explain their son’s autism other than it was compounded by severe and frequent seizures.  When their son was tested, however, they learned that Levi’s cells harbored a mutation that affected the way his cells produced energy.  The Jensens now had valuable information to help treat their son.  For individuals with his particular type of mitochondrial dysfunction, certain seizure medications can cause serious side effects.

In a way, Levi Jensen was lucky. He lived near a large research center that specializes in mitochondrial disorders which is funded by Autism Speaks to investigate the role mitochondria play in autism spectrum disorders (ASD). The diagnosis of mitochondrial disorder or dysfunction is difficult. Multiple tests, often including an invasive muscle biopsy, are required.  How many other individuals with autism might benefit from a deeper understanding of how their cells use energy?

A new study released today in the Journal of the American Medical Association (JAMA) reveals that children with autism may have more trouble fueling the energy demands of their cells due to dysfunctional mitochondria. In this new Autism Speaks-funded study from UC Davis, blood samples from 10 children between the ages 2 and 5 years old and diagnosed with autism were compared with matched control samples from typically developing children.  The investigators found evidence of “breaks” in the cascade of enzymes that mitochondria use to create energy in 8 of 10 autism samples, but no control samples.  They found evidence of a mutation in a gene that supports mitochondrial function, also only in the autism samples. Lastly, in most of the autism samples, there were extra copies of mitochondria. The over-proliferation of mitochondria may also be a sign that individually the mitochondria are not working optimally, and are compensating for reduced function from each mitochondrion by producing more mitochondria overall.

Previous studies have shown that breaks in mitochondrial function can lead to a host of disorders, and the energy-demanding brain can be particularly affected. However, none of the previous autism studies has shown as high a proportion of impaired mitochondrial function as the current study.  Cecilia Giulivi, Ph.D., the lead researcher on the study and a professor of Molecular Biosciences in the School of Veterinary Medicine at UC Davis, was drawn to research abnormal energy metabolism in autism because several symptoms of ASD overlap with mitochondrial diseases.

“We wanted to test the hypothesis in a direct way: is there a mitochondrial dysfunction in material readily available from children with full autism syndrome?” says Giulivi. The research team chose to look at white blood cells—lymphocytes—because they are a type of cell that has significant quantities of mitochondria. Drawing blood is much less invasive than obtaining a muscle biopsy, but traditionally mitochondrial function has been difficult to assess in blood because there are relatively few mitochondria in blood, compared with other body tissues. In fact, red blood cells have no mitochondria at all.

While these results are an exciting new development for both this area of research and for families, it is important to remember that this is still the edge of science and not yet a clinically-useful set of tests. However, if replicated, these tests could make screening for mitochondrial dysfunction much more accessible.

Dr. Giulivi and colleagues are already taking the next steps to follow up this research.  They are studying the families of children with autism to try to understand the mechanism that causes the mitochondrial deficiency. The samples are part of a larger study (CHARGE; Childhood Autism Risks from Genetics and the Environment) in which the investigators are already measuring both genetic and environmental influences on autism risk.  Adding mitochondria to that mix will be especially helpful.  Dr. Giulivi was also quick to add a note of deep appreciation for all the families that participated in the study, saying “Without their participation, we couldn’t have done it!”

Indeed the enthusiasm for research participation often works both ways.  The seizure medication Levi had been taking—Depakote—seemed to make Levi very drowsy. At three years old, Levi was sleeping and napping for 16 hours of the day. His mitochondrial specialist switched medication right away due to concern of an underlying mitochondrial disorder for which Depakote produced severe side effects.

The Jensens are thrilled to report that Levi now has more energy than ever, has regained words that he lost prior to the medication change, and is generally functioning at a much higher level.  For Levi’s parents, Curtis and Alaina Jensen, learning about Levi’s mitochondrial disease helped them gain an understanding of metabolic functions and sparked creative ways to make special considerations for the remaining challenges Levi faced.  Alaina says, “We have found that exercise has been a big key for Levi to feel good and increase his energy and stamina.  It took a long time for him to build up the endurance to play, but it has been worth all the effort.  With a combination of the right seizure medication, supplements, exercise and diet, we now have a very happy boy.”

Click here to view the press release on this new report.

  1. November 30, 2010 at 5:38 pm | #1

    I can’t access the text of the JAMA paper and have three questions.

    1. What were the selection criteria for this subset of 10 children?

    2. What is “full autism syndrome”?

    3. Is the potential conflation of autism *with* mitochondrial syndrome addressed in the paper, as it is noted in the above (“several symptoms of ASD overlap with mitochondrial diseases”)?

    Thanks.

  2. Katie Wright
    November 30, 2010 at 9:02 pm | #2

    Beautifully explained.

    My understanding is that “full autism” is severe, medically involved ASD w/ significant loss of function via regression. I may be wrong, I am just guessing.

    My son has mito disorder as well and was prescribed Depakote- also a nightmare and so difficult to wean him off. I like this study because these scientists are working on the causes of the symptoms and viewing ASD as dynamic and treatable w/ right biomedical intervention rather than old paradigm as genetic and inevitable.

  3. Alisha Davis
    December 1, 2010 at 3:10 am | #3

    That is great guys, good job! : )

  4. Sarah
    December 1, 2010 at 8:14 am | #4

    AWESOME!!!! Happy, happy tears.

  5. December 1, 2010 at 10:34 pm | #5

    One of the critical factors on mitochondrial dysfunction is screen for it in children. As many may know, one of the primary tests done to look for mito issues is a very invasive and painful process of muscle biopsie, As Geraldine Dawson pointed out on this study:

    “It is remarkable that evidence of mitochondrial dysfunction and changes in mitochondrial DNA were detected in the blood of these young children with autism…One of the challenges has been that it has been difficult to diagnose mitochondrial dysfunction because it usually requires a muscle biopsy. If we could screen for these metabolic problems with a blood test, it would be a big step forward.”

    Recently, a company called Medomics developed a blood test for many mitochondrial DNA issues:
    http://www.medomics.com/sites/default/files/docs/assays/MitoDx_Assay_Summary.pdf

    We NEED more screenings for potential mitochondrial issues in kids diagnosed on the spectrum. With the ability to screen for mito issues through a painless, non invasive blood test, there is NO reason why most children diagnosed on the spectrum should not be screened. I am not a sales rep, I am a parent of two autistic children who sees the potential and wants change in the way the mainstream medical community deals with its autistic patients…

  6. Katie Wright
    December 2, 2010 at 3:46 pm | #6

    Bill I agree but it is much easier to just prevent the problem.

    The VAST majority of people w/ mito disorders are asymptomatic. In 90% of cases isn’t UNTIL an environmental exposure triggers them that problems begin.

    My son’s mito disorder is documented- just like Hannah Poling- but the damage is done- we only have the ability to manage the aftermath. The mitochrondria is extremely sensitive to toxins – yet there is no rational, feasible way we can pre screen every American baby – we must make our vaccines safer, with fewer toxic adjuvants

    • Laura Cox
      December 3, 2010 at 8:29 am | #7

      Katie,

      Same here. In fact, it was the Hannah Poling case that had me look at mito. When I saw that my son’s medical problems fit the profile and we had an expert right here in Houston, I took him in to see what the doc had to say. He was ultimately diagnosed with significant mito dysfunction. One of the most interesting questions the doctor asked on the first appt was “Did your son lose speech after the MMR?”. I had to say yes. I had not brought up the subject of vaccines, not knowing how this doctor would react. Biomedical treatment and targeted nutritional supplementation has had a tremendous positive effect on my child’s health and functioning.

      It is good to see Autism Speaks finally acknowledging a physical correlation for autism. The brain is a huge energy organ and if the mito are unable to power it, you are going to have autism symptoms.

      • Joan
        December 3, 2010 at 1:51 pm | #8

        Hi Katie,

        You mentioned nutrional supplements for yur child having a positive benefit on their health and functioning. Could you kindly share which nutritional supplements you found helpful.

        Joan

  7. December 2, 2010 at 6:19 pm | #9

    “Bill I agree but it is much easier to just prevent the problem.”

    Is it though? I’m not going to pretend to know much of anything about mitochondrial issues other than what have learned on the ‘virtual’ street, but I would count in as environmental triggers things like a spiked fever, lack of sleep, exposure to a plethora of household chemicals, food additives, general stress, ANY type of anesthesia and probably a dozen other issues along with vaccinations and loads per visit. You are also obviously painfully aware of the socio-economic factors involved in revamping a system and process that is a cornerstone of worldwide governmental health initiatives. Much easier to prevent the problem? While it is a wonderful sentiment, the practicalities of it are years away: both scientifically and socially.

    In the meantime, we have children who could benefit from knowing what medical issues are going on. Our medical community is almost invariably giving the diagnosis of autism, then moving on with no investigation of potential medical issues that our children may have. Again, I am no expert on mitochondrial issues, but from what I’ve read, from 2 to 5% of autistics MAY have mitochondrial issues…at a BARE MINIMUM! What other disease that affects 1 in 20 people is NOT screened for? One of the red flags that doctors are supposed to use as a guideline to suspect mitochondrial dysfunction is regression or developmental delay. NOT ONE of the doctors we have seen for my 8 year old daughter, who clearly regressed, recommended we pursue it.
    One of the reasons I feel this was not brought up, is the painful and invasive process of muscle biopsy. With tests like the one I mentioned, we can take that concern off the table, and get doctors to CONTINUE to diagnose and investigate, instead of stopping at the word autism and leaving parents with the idea that most anything that is ‘wrong’ with their child can be attributed to autism.
    As with most of us parents of autistic children, I could go on for pages with the injustices we suffer from the mainstream medical/insurance establishment. But screening autistics for mitochondrial dysfunction, especially those who regress, is one area that we could get almost universal acceptance within our autism community, irrespective of causation beliefs or vaccine reform. We need to move medical treatment of autistics forward, and screening for mitochondrial dysfunction in autism is one area that should be mandatory and universally accepted…

  8. December 3, 2010 at 9:30 am | #10

    Our daughter with autism, now 20, surely had mitochondial disease. None of her drs at Kennedy Krieger, DUKE or MUSC have ever discussed this with us. Where do we go for help? It’s not fair to her.

  9. Shon
    December 3, 2010 at 10:02 am | #11

    It seems we are gettting closer and closer to finding the basis of Autism or rather the combo of issues that causes Autism I think we can all agree that if there is an overload of physical, enviornmental, stressors to our children it has a definite lasting effect. Its funny, my son lost his speaking ability after getting a high fever from an MMR shot……and now to this may be contributed to mitochondrial issues.

    • Debbie
      December 5, 2010 at 3:43 am | #12

      Shon,
      My son at 18 months of age, lost his speaking and social abilities as well, after receiving the MMR.

  10. Mohan
    December 3, 2010 at 10:06 am | #13

    It is mentioned that the Jensens switched medixation from Depokate to another seizure medication. Can that be shared so we know which other seizure medication helped.

  11. D. Mee
    December 3, 2010 at 12:25 pm | #14

    Our son is 25 yrs. old and we have discovered this year that our family has the MTFHR gene defect that is involved with B vitamins inparticular at the mitochodiral level. This is definately helping us understand his health, with his particular sensitivites to medications, etc. This was discovered with a simple genetic test – bloodwork only. A geneticist can help council which is the next step for our family.
    Does anyone know what medication the Jensens used successfully for seizures? My son is currently having some serious issues with Depakote.

  12. brian kerwin
    December 3, 2010 at 1:06 pm | #15

    my son is 19 1/2 year , he would qualify as severly autistic but he is sick, cant eliminate toxins. we intentionally harm this group when we treat thier symptoms as behaviors. autism treatment center should be understanding why these symptoms exist, find solutions. We should recognize the sick are collateral damage , we have done them harm, whenever a autism organization treats thier symptoms like behaviors.

  13. Megan
    December 3, 2010 at 1:07 pm | #16

    Bring a copy of this article to your neurologist and they should be able to answer your questions about mitochondrial dysfunction and Depakote or at least be able to find someone who does know.

  14. Beverly
    December 3, 2010 at 1:13 pm | #17

    Do the supplements replace the missing mito enzymes? And if so what are they? Also, how does the dietary program work?

  15. Timms
  16. MarkH
    December 3, 2010 at 1:30 pm | #19

    Shon :
    It seems we are gettting closer and closer to finding the basis of Autism or rather the combo of issues that causes Autism I think we can all agree that if there is an overload of physical, enviornmental, stressors to our children it has a definite lasting effect. Its funny, my son lost his speaking ability after getting a high fever from an MMR shot……and now to this may be contributed to mitochondrial issues.

    I don’t think that’s the case at all. You have to prove why it’s happening and also why it’s not happening in others to draw a conclusion. It’s interesting, but this is a very small sample and hopefully the initial finding will lead to a larger study. To run out and put your child on medication for something they may not have is irresponsible.

    Our children may all share the same diagnosis but I find the symptoms, conditions, histories and behaviors to all be vastly different. My son exhibits all the classic behaviors of Autism but he didn’t suffer regression, or react to vaccines, or suffer seizures, or environmental reactions. It makes me wonder sometimes if we are all talking about the same thing. Or maybe Autism is so complicated that we are actually looking at a dozen different disorders that share SOME common traits and possibly all have DIFFERENT causes.

    • Debbie
      December 5, 2010 at 3:42 am | #20

      My son lost his speaking and social abilities along with other abilities, 1 to 2 weeks after receiving the MMR vaccine.

  17. GWu
    December 3, 2010 at 2:12 pm | #21

    Hi Folks,

    Recently, a friend of mine who has a child with autism shared with me about a formulation that he had come across on a website (www.n-met.com). Apparently, the website introduces a formulation called N-MET invented by a former professor from Cornell and his colleague. The professor discusses how the formulation provides supplements that would increase energy production in mitochondria. After reading this article and looking at the website, I have a better appreciation of the cause of autism. The formulation now makes intuitive sense. My friend told me that his child has noticeably improved (better focus and calmness) since taking the formulation.

  18. Eleanore
    December 3, 2010 at 4:18 pm | #22

    My friend sent me a link to this article. I have a 7yr old diagnosed with Asperger’s syndrome, as well as two younger children who we know have an unknown metabolic disorder more than likely caused by a mitochondrial disorder. It is something that has never been seen before, and they still can’t figure out where the problem is. Their Geneticist/Metabolics Dr has been wondering for the last year if our oldest may also be suffering from a mitochondrial disorder. I will definitly be forwarding this on to their Dr, but I’m very anxious to see more information on this.

  19. Boscia1
    December 3, 2010 at 10:01 pm | #23

    Thank you for this as it is timely for my family. We just got the diagnosis yesterday as Mitochondrial disorder. We have had Autism as her working diagnosis for 7 yrs but our Neurologist knew that it didn’t add up. It spanned 7 months from the onset of the first consult in which mitochondrial was presented as a possibility,to the final muscle biopsy. It was along process but Moms and Dads you must persevere. We now have a definitive answer. The problem remains that this disorder is complicated for all involved to understand. If there are any studies that we could participate in, please let me know at Boscia1@gmail.com.

  20. Jenny
    December 4, 2010 at 8:42 am | #24

    SOme peopel are wondering about alternatives to depakote. I’m not a doctor, and I have no idea what the Jensens switched to. However, I am an adult Aspie with seizure issues – I get them from fevers, stress, meds, etc. I have been on a rather high dose of Neurontin (gabapentin) for over a decade now and it’s done wonders. I function! In addition, my doc found that taking most or all of the dose at night still controls the seizures and helps me be alert in the day.

  21. December 5, 2010 at 12:44 pm | #25

    We went through a few to find what worked for him. First we tried Zarontin which gave him hives. Next we tried Keppra (a good choice for children…but sometimes affects ASD kids negativly), but he cried almost non-stop for 3 weeks. It had been such a difficult transition going through the medications, we tried no medication to see what would happen. Over the course of 4 weeks, the seizure activity returned and increased so much that he was having his more severe behaviors return…Biting, Hitting, Pushing, Tantrums, Severe Rocking, Chewing, Head Banging, etc. Last we tried Trileptal. It greatly decreased the seizures, he was much happier, more energy and much more engaging….however since it wasn’t fully controlling the seizure activity (show by EEG) we decided to add Lamictal. Lamictal can have serious side effects and so we increased the dosage very slowly. He has now been on the full dose for about 6 weeks and is doing very well. We have not yet had a follow-up EEG to confirm complete control, however he is doing the best he’s ever done. For the future the plan is to slowly remove the Trileptal from his protocol and just stay with the Lamictal.

  22. Val
    December 5, 2010 at 2:39 pm | #26

    My 16 year old son w/autism has been on Lamictal for over a year and half. At 14, he started having seizures and typically occuring within an hour of him waking. We did have to increase the dosage gradually over months to ensure he was at the correct dosage. In fact, we went 7 months with no seizures and thought we were smooth sailing. They have returned at once a month, again within an hour of him waking. Recently, his doctor moved his night time dosage to bedtime, and 50mg more than his morning dosage. We are now 2 months with no seizures. Hoping we can get to the correct dosage and timing to go seizure-free. Next stop, check into Mitochondrial disorder.

  23. Linda Safran
    December 8, 2010 at 3:46 pm | #27

    My daughter is 20 years old. She has developmental delays and pdd. Over the past month she has not done well at her internship at the hospital cafeteria. She complained she wasn’t feeling well, sat down, and refused to work. She started a new internship today that is in a quieter setting. She also does a lot of complaining at home. She is slower to get up in the morning, and complains of all sorts of ailments since she wants to stay home from school. When she exercises at the gym, she complains that her legs and arms hurt. I took her to her psychopharmacologist who increased her Prozac. I took her to her internist who removed some wax from her ears. Could she have mitochondrial disorder? I heard there is a blood test for this at Children’s Hospital in Boston. Is there any treatment for mitochondrial disorder?

    • December 13, 2010 at 2:34 pm | #28

      Linda: I was drawn to this blog by a story on MSNBC regarding the UC study on Mitochondrial Dysfunction in Autism. As your daughter is an adult I can confidently share with you significant research by some brilliant and committed scientists which might lead you to an solution for your daughter’s complaints. There has been research on mitochondrial energy production and also on cellular inflammation which is caused by oxidative stress. Please contact me at: trainermarty@gmail.com if you would like me to share this research. I truly believe it would be worth your time or I wouldn’t have taken the time to reply to your post.
      Best Regards…Martin Greene

  24. December 13, 2010 at 2:24 pm | #29

    There is a lot of work being done in the field of oxidative stress and energy production in the mitochondria. What I’ve learned through my two years of research is that adults as well as children need two critical elements in order for the enzymatic reaction to occur in the mitochondria which creates ATP (energy) as well as glutathione to protect the cell from the resulting oxidative reaction. Those are Ribose and Cysteine. If there is not enough ATP or Glutathione the intracellular enzymatic activity in the mitochondria will be diminished. Read the work of Dr. Herbert Nagasawa, who has spent the last 25 years studying glutathione and has 18 peer reviewed articles (over 100 in his illustrious career) and 25 patents on Riboceine, which allows the cell to increase it’s own natural ATP and Glutathione production. I’m not a doctor, just a Baby Boomer who is curious about the optimum ways to stay healthy without drugs and passionate about helping those with Autism Spectrum Disorders and their parents. If you would like to learn more I can provide Dr. Nagasawa’s research and recommendations along with work that’s been done with supplements that have increased cellular performance (energy) in children and adults with ASD by increasing ATP and Glutathione levels.

    • Shannon Smith
      December 27, 2010 at 11:39 pm | #30

      Where can I find Dr. Nagasawa’s research and recommendations, as I have just begun the journey into mito dysfunction and oxidative stress to help my son who is 9 and inherited a dup15q11-13 chromosome abnormality from me, which has been identified as a mitochondrial energy deficient phenotype associated w/ autism. No surprise as my family history presents with many associated illnesses and disease. Would love any info you have…thank you in advance.

      Shannon Smith

  25. mary jane walsh
    December 14, 2010 at 10:58 am | #31

    What was the seizure medicine that replaced the Depakote ? I am a high school nurse and would love more info .

  26. martha
    December 22, 2010 at 8:55 am | #32

    Iam an adult with Aspergers and Fibromyalgia. For years I have wondered if there was a connection with Autism and physical complaints such as Fibromyalgia. Could Mitochondrial Dysfunction be the cause of my physical problems?

    • Deb M.
      December 22, 2010 at 9:52 am | #33

      To Martha – I have been diagnosed with Fibromyalgia as well and have come to learn that the muscle pain and fatigue was the result of medications that I was taking. Once off the meds I have improved dramatically.

    • Deb M.
      December 22, 2010 at 9:53 am | #34

      It is my understanding that Lamictal was the replacement medication.

  27. martha
    December 22, 2010 at 12:50 pm | #35

    What type of medications were you taking? I am on a lot of medication, but had all the fatigue before medication.

  28. Robin R.
    December 28, 2010 at 6:01 am | #36

    I was wondering if anyone knew if the Mitochondrial Dysfunction could also lead to a problem with too much energy. I have two daughters with Autism one who is 10 and one 7. The 7 year old is hyper beyond your wildest dreams. We have found very few medicines for hyper-activity that have worked, and the ones that have worked made her scream and cry all day. I was just wondering if there have been any studies showing the opposite to also be true.

    • Wendy
      April 16, 2011 at 7:48 am | #37

      Robin,
      I have a 10 year old son on the spectrum. He also has adhd, central auditory processing disorder and asthma. We have had him on many different meds through the years. He was on heavy duty anti-psych meds like Risperadol and later abilify. Each worked great for about a year. When he had a growth spurt we tried to increase meds and he started having tics. This happened on each med. Our Neurologist said the meds wouldn’t do that…but we increased meds tics increased…got off meds tics…went away. We tried Ritalin one day and got the same reaction as your daugther. He screamed and cried all night. I never gave it to him again. We now take him to a child psychiatrist. She put him on a blend of meds rather than one heavy duty medication. He is now doing great on Prozac for the mood swings and Strattera for the adhd. I am sure that doesn’t answer your question but just wanted to let you know that my little guy also deals with adhd. He does get tired out after a little strenuous excercise though. I am sure that is from the asthma. But otherwise he used to bounce around all day long. Climbing on everything. Even though he is much more calm he still has his fidgety moments. He knocked a tooth out the other day swinging between his bed and dresser.

  29. March 1, 2011 at 1:00 am | #38

    Joan :Hi Katie,
    You mentioned nutrional supplements for yur child having a positive benefit on their health and functioning. Could you kindly share which nutritional supplements you found helpful.
    Joan

  30. Alaina Jensen
    March 6, 2011 at 1:10 pm | #39

    Joan :
    Hi Katie,
    You mentioned nutrional supplements for yur child having a positive benefit on their health and functioning. Could you kindly share which nutritional supplements you found helpful.
    Joan

    For Levi’s Mitochondrial Disease, we have found 3 supplements very helpful with Mood,, energy and stamina. They are Ubiquinol (more readily absorbed form of CO Q10), B-100 (high dose multi B vitamin), Acetyl-L Carnitine (this has also been very important with his epilepsy and seizure medication). We have tried periods without the supplements, all at once and one at a time, but they all have a noticeable and significant effect.

  31. July 7, 2011 at 12:38 pm | #40

    “The Jensens are thrilled to report that Levi now has more energy than ever, has regained words that he lost prior to the medication change, and is generally functioning at a much higher level. For Levi’s parents, Curtis and Alaina Jensen, learning about Levi’s mitochondrial disease helped them gain an understanding of metabolic functions and sparked creative ways to make special considerations for the remaining challenges Levi faced.”
    How exciting are these developments in the area of research for autism? I hope more clinical tests can be done to make screening for mitochondrial dysfunction more accessible for parents of children with autism spectrum disorders.

  1. December 1, 2010 at 8:53 am | #1
  2. December 16, 2010 at 4:17 pm | #2
  3. January 14, 2011 at 6:09 pm | #3
  4. April 7, 2011 at 12:48 pm | #4
  5. May 12, 2011 at 9:32 pm | #5

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