Friday, May 13, 2011

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:

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.


________________, 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]