Mitochondrial Dysfunction ...

Well, I finally initiated mitochondrial testing on T a few months ago, and the initial results are back, and they were abnormal. In case someone else may find this helpful, I'm going to reprint the results I got at the end of this post, with names removed.

If you have a child on the autism spectrum, and you have not yet seen or heard anything about the pilot study done at UC Davis that tested 10 kids on the autism spectrum and found dysfunction in 8 of them, then you should read this article from Neurology Today describing the study. (Google will also turn up a whole lot of other news articles on the study, it made a pretty big spash.) Here is a quote from the article, which also quotes the study itself:

The children with autism had evidence of mitochondrial abnormalities across several tests compared to the controls. The mitochondria of the autistic children had reduced nicotinamide adenine dinucleotide oxidase activity, an average of 4.4 versus 12 for the normal controls (p=.001). Six of the 10 autistic children also had lower complex I activity and eight of the 10 had higher plasma pyruvate levels than the controls. By contrast, only two of 10 had higher lactate than the control children. The mitochondria from the autistic sample also had higher rates of hydrogen peroxide production compared to controls.But with all of these findings there is still no indication, at least from this study, whether these mitochondrial abnormalities are “a cause or a consequence of another process that accompanies autism,” said Dr. Giulivi. Altered energy metabolism, she explained, “may influence the social and cognitive deficits in autism.

“Mitochondrial dysfunction could greatly amplify and propagate brain dysfunction, such as that found in autism, given that the highest levels of mitochondrial DNA abnormalities are observed in post-mitotic tissue with high energy demands (such as the brain),” said Dr. Giulivi.

The plasma pyruvate and lactate-to-pyruvate ratios suggest pyruvate dehydrogenase (PDHC) deficiency and indeed when they looked at PDHC complex activity they found half the levels in autistic children than in the controls. Defects in PDHC lead to problems in energy metabolism because pyruvate is one of the main fuels for mitochondria.

These mitochondrial problems can create less capacity for the cells to produce ATP, the energy currency of the cell that pays for all cellular work. In the brain, as well as heart, ATP only comes from mitochondria. (Outside of the brain, lymphocytes can take their energy from mitochondria and other independent pathways.)

Although I had been thinking about mitochondrial issues for some time, it was really that study that prompted me to finally take T and have him tested.

I should say that the kind of testing that the doctor usually does initially costs thousands of dollars, but as T seemed "stable," and we were uninsured, we have been piecemealing the testing. We started with buccal swab testing, because it was available for free, thanks to the fact that the doctor we went to see is working with a researcher who is doing a study. The "gold standard" for a long time for a mitochondrial diagnosis has been muscle biopsy, which is extremely invasive (and expensive!). A very small sort of pilot study however recently suggested that the buccal swabs are almost as accurate, maybe as accurate. Read more about that here: http://www.mitoaction.org/blog/muscle-biopsy-testing-mitochondrial-disease.

If you have a kid with a mitochondrial dysfunction, it has a lot of implications for how you care for them. First, there are supplements (often called the mito cocktail) that can help some kids. But secondly, there are things you have to be extra careful about:

1) avoid fevers. Fevers consume a lot of energy, and that means they can cause a lot of damage. This is the mechanism by which vaccines can become a problem, if they cause a high fever.

2) avoid the heat, because temperature regulation consumes a lot of energy. I have read about cooling vests and cooling hats that might be helpful.

3) be careful about anesthesia. I don't know the details, but it can be dangerous also.

4) keep them very well hydrated, and they may need nutritional intervention.

That's about all I have time to share today.

Here is what the doctor sent me:

Hi --------,



Well, it looks like [T]'s swab studies were abnormal. See below. Although __________ would like to repeat them just to confirm the abnormalities, they are suggestive of mito dysfunction.

Having said that, I think we should repeat them, and look to get the other first Tier of tests on him (lactate, pyruvate, coQ10 and carnitine). Once they are collected we can start him on the cocktail. I’ve seen a number of the recent ASD kids who have abnormalities on their enzyme studies do much better on the cocktail.

Let me know if you have questions.

Regards,


________________, MD

~~~~~~

[email from researcher who did buccal swab testing, to doctor, who kindly forwarded it to me:

Dear [Doctor].


My findings with [T]'s buccal swabs revealed a significant deficiency in his buccal complex IV activity (at roughly 26% of normal control levels) and normal levels of his complex I activity. His overall buccal mitochondrial content (as gauged by the activity levels of mitochondrial enzyme citrate synthase) was also above the control range suggestive of an adaptive response to a mitochondrial bioenergetic abnormality.

Given the possibility of shipping and handling effects, the extreme lability of these enzyme activities as well as the extreme heterogeneity of this kind of mitochondrial defect, I would recommend retesting a new set of buccal swabs from [T] within the next few months to see if the deficiency in his buccal complex IV activity reported here is indeed a repeatable finding.

Thanks as always for the opportunity to analyze your patients.

Yours truly,

[researcher doing the testing]

more funny things that T said

This morning, T came running into the kitchen to show me his Mr. potatohead: "Mommy, that's a CHOCOLATE potatohead." I said: "That sounds yummy. Are you going to eat it?" "No. It's just a potatohead. It's not chocolate, or a potato."

everything's gonna be OK (verbal at 4)

I hardly ever post any more, and I think I need to explain that it's because now I know that T is going to be okay, and I have been able ... SOMEWHAT ... to move into something like a more normal existence. I'm not sure how many people stumble into this site looking for answers, but I want to share for the record just how great T is doing now that he is 4 (birthday Feb. 24), because when he turned 2 I was really really scared.

His eye contact is not great, and he says some odd things, but he is quite verbal. When he gets mad, he says, "Mommy, go away! You'd better get out of here." When he's tired he says, "Mommy, pick me up and I will close my eyes!" He can answer "where" and "who" questions, and he's ALMOST mastered "why" and "because" and "how."

Does he still happily play in the sandbox for a really long time? Yes. But earlier today, he ran into the house crying, and said: "I need a napkin!" I said, why? he said: "S dumped water in my sand. I need a napkin to dry it off. Dry it off, mommy!"

The other day he said: "Mommy, I wanted some berries and you said no, and I was really SAD! But then you gave me some and now I am happy!"

Quirky? Definitely. But he's going to be okay.

observers and eye contact

I haven't posted in a while ... I wound up with so many posts saved up in my head that I couldn't get them all down. But this I had to post, in case anyone ever reads it. In this study involving bonobos (a kind of primate considered by many to be the most similar to humans), the authors state that a bonobo was far more likely to make eye contact if there was no third individual observing. That is, if a third bonobo was looking at them, the first bonobo was likely to turn away from a second bonobo, and not make eye contact. I find a lot of interesting things to think about in that.

Meltdowns and a funny meltdown story

I've been reading and thinking a lot about meltdowns lately. T was being evaluated by the county the other day when he had a huge meltdown. The school psychologist wanted me to ignore him. That's not my way. Not that I have solved the Meltdown Problem, for anyone out there who is searching for a solution. But I don't believe in ignoring it.

I mean ... let's think about this for a minute. We have an autistic individual with a severe deficit in the domains of language and communication. He is communicating wants and desires and feelings ... so I should just ignore him?? This is one of the most absurd pieces of advice I have received since my son's diagnosis, in my opinion.

But this is apparently a widely shared view. I got the same piece of advice, I now recall, from some other county employee when he was 20 months old. I thought it was ridiculous then and I am really glad I didn't take it.

As it happens, T is doing GREAT despite his challenges. He makes terrific eye contact, hugs me and has even on occasion been known to tell me he loves me. Well, I can't take all the credit for that, but I personally think that if I had taken these people's ridiculous advice, he would probably want very little to do with me.

Anyhow, the point is that I HAVE been re-thinking this topic lately, and meditating on what causes these things which are so much more than temper tantrums. One thing I think is that T has the ego of an adult. According to this entry from the Eides, it may even be that autistic children wind up with difficulties acquiring language because the prefrontal cortex has matured too early. Apparently, an immature prefrontal cortex may (some people theorize) make it easier to learn some kinds of information. It seems that the prefrontal cortex is where a person develops their will and volition. See this, for example.

And this explains a lot. T's ego is very easily insulted. A lot of little kids get upset when you take their toys away, but for T it's more than the loss of the toy. I can tell that. It's the powerlessness of being at the whim and mercy of someone else that he finds galling and he just can't take it. If he wants something and it's not in the house, he wants to just go to the store and get it. Well, how can I blame him? I would too, but of course he's not old enough to drive. So there is the crux of it.

I'm still not sure what to do with this information, but these musings of the last couple of days made the following story much funnier.

T is very taken these days with a scene from Dora the Explorer in which Benny the Bull carries around an armfull of stuffed animals which he refers to as "my guys." At the dollar store, T grabs all these little Halloween characters and calls them "my guys" (which was very cute and funny), but then naturally he wanted to take them all home. My husband tells him he can only have one and buys him the bat. [insert meltdown here .. ok, the meltdown itself was not that funny.] But in the aftermath:

T (repeatedly): "I want the witch and the ghost and the pumpkin and the bear AND the bat, TOO."

Me: "You can't have everything you want."

T says : "I want to have EVERYTHING I want."

Truer words, never spoken.

Quick update re. prednisone

I just never seem to have time for blogging anymore, but I wanted to provide an update to my earlier posts about prednisone. T had another respiratory episode recently and had to do another 5-day course of prednisone. However, I did not see any obvious changes to his language abilities this time. I don't know if this is because my previous observations were a fluke, or perhaps because this time he received pills rather than liquid. That shouldn't matter, except that he chewed the pills instead of swallowing them, which means he didn't get quite as much of it. Perhaps my previous observations were coincidental, then, or had another cause. One other thing is that because of the timing of his first two doses of prednisone last time, there was a period of time in which he had much more prednisone in his system. Also, I still to this date have not had a single instance of the kind of joint attention he exhibited on that one occasion (where he pointed to an object and then alternated his gaze with me and the object, most remarkable).

About hormones and orchid children

One of my most recent (and yet also oldest) worries has been the hormones. So many autistic children have hormonal imbalances it seems, so we are not alone. But since he was an infant, T has had near constant erections. The pediatrician consistently discounted this as being of any significance, but I have a NT child also, so I know this is abnormal. Given the number of other kids with excess testosterone, I feel confident this is a problem although I have not bothered to have T tested.

I haven't had him tested, because it is expensive and will, I believe, lead nowhere unless I'm prepared to give him lupron, which some parents do. It is extremely controversial, of course, although I think it is very shocking the extent to which these parents are villified and mocked by others. There are several parents in my autism support group whose children hit puberty at the ripe old age of 8, and I think about this a lot as T gets older.

Am I possibly making a mistake by not addressing the excess testosterone? I don't know. It seems risky to me, there is just so much we don't understand. Although I understand that testosterone and other androgens can cause damage, it seems to me that for all we know, they might also be elevated for a reason. Maybe they have some other effect that is beneficial -- how do we know?

After hours of reading, I still don't really understand much, but I have come away with one fact that I found very interesting: According to Allan Mazur, although testosterone has been linked to problems like aggression, excessive risk-taking, delinquent behaviors, and the like, it turns out that these outcomes are all context-dependent. They are influenced by things like:

1) the quality of the child's relationship with his parents; and
2) the behaviors of his peers.

Dr. Mazur speculates that higher testosterone might confer social benefits under the right conditions, and I find that very interesting indeed.

(See this article, this article, and this book for more.)

Maybe this extra testosterone is just more proof that my son is an "orchid child," who just requires that extra care to bloom. In case you haven't read this article, an "orchid child" is not some weird new age thing, it means that some children have unique attributes that make them extra-sensitive to their environment -- they need a "SuperMom" -- without one they will not succeed, but with one, they may flourish even more than their peers (called "dandelion children" by the author).

Here's another interesting fact: although we tend to focus on testosterone as a cause of behavior, it appears that testosterone levels are also influenced by experience. Dr. Mazur calls it "reciprocal causation."

It's probably obvious why the "orchid child" premise is a favorite theory of mine.

At any rate, there certain seems to be a fairly wide consensus that autistic children are more vulnerable to environment than others, and a lot of researchers (like these) are busy trying to find that environmental trigger. I have read suggestions that there are links to stress in the mother, infections, vaccines of course (by some), autoimmune disorders, even cable television. But I wonder if they are focusing too much on looking for a physical trigger.

Dare I wonder aloud (so to speak) whether parenting matters? I know this is kind of taboo to bring up. If anyone is reading this, I'm sure you are saying, "but that refrigerator mother theory was discredited long ago." But I am not in any way suggesting that a lack of affection by mothers causes autism. But I DO wonder whether we don't have fewer REAL "supermoms" than we used to a few decades ago. Surely we do.

How many of our children are in daycare and preschools that are not top notch? How many mothers can afford to stay home or afford to put their children in really top notch centers with very low teacher to student ratios? We were advised by the "experts" to interact with T at least once EVERY 5 MINUTES. And even now that he is 3-1/2, not to leave him anywhere with a ratio of less than 3-to-1. Who can do that? Who can afford that?

30 years ago, were there more mothers living at home, with help? I'm not sure, but I wonder. Is it possible that more mothers had mothers, sisters, even older daughters? Is it possible that life was just radically different?

I have to wonder whether there aren't some children -- NOT all of them, they are clearly not all the same -- but SOME children, who require never-ceasing, endless, copious, exhausting superhuman amounts of attention. OK, I don't have to wonder, I KNOW it, because that is my son. He requires it or he will not develop. Were there times when I couldn't do it? You betcha. I'm not a refrigerator mom, but I am human, and I have limited resources.

When I get tired and I give myself a break it takes the blink of an eye for T to start "checking out." I don't know why. But the point is that he does. Less and less now, but he does.

Fortunately, I have been blessed enough with the ability to earn a true livable salary working only 15 hours per week, with an amazing husband who also works part-time and is a full-time, second primary caregiver the rest of the time. But where would we be without those things? I truly don't know, but in my heart I suspect very much that our T would be on the severe end of the spectrum.

Well, that's sort of an aside, and I'm sure that to some degree, I just want to believe that what I does matters. That it's in my power to just grab him and hoist him on up into high-functioning adulthood. I just do want to believe that, and I won't lie about that.

And I don't really know how severe T is or would be. I will say that Jayden, the star of "Bye" (which I really recommend if you haven't seen it, it is only 10 minutes long), whose mother says he was diagnosed as "severe," reminds me very much of T when he was that age. Not every minute of the day, maybe, but there is nothing about Jayden that is unfamiliar to me, although T was diagnosed with PDD-NOS instead of classic autism, and he was labeled "moderate" instead of "severe." A few months ago some county therapists expressed the idea that he seemed more "mild" to them than "moderate," so maybe I'd like to take some credit for that, but I don't know. I didn't have that much respect for the therapists in other respects, so I guess like everyone else I just believe what I want to believe.

So ... what does this have to do with testosterone? I don't remember anymore, except that I'm clinging to some way of looking at things that gives me the power to influence the outcome without giving my son drugs.

Maybe being a supermom could mean that his extra testosterone won't get him into trouble. Maybe if I could just do everything just right (OK, I know I can't be perfect) -- it will all turn out okay, or even better than okay.

On the other hand, I'll be singing a different tune if he starts sprouting body hair next month.