Sunday, September 2, 2012

FIND YOUR POTS CAUSE: Mitochondrial Disease 101 (Guest Post by Hannah!)

Global Mito Awareness Week is September 16-22.  Mito can cause POTS symptoms, and other types of autonomic dysfunction.

"Mitochondrial cytopathies are a diverse group of inherited and acquired disorders that result in inadequate energy production. They can be caused by inheritable genetic mutations, acquired somatic mutations, exposure to toxins (including some prescription medications), and the aging process itself." (1)
I'm very excited to have an amazing POTSy teen that I met and have gotten to know a bit through Facebook offer to write about her probable POTS cause, Mitochondrial Disease. Her name is Hannah, and she just started her Freshman year at UNC Chapel Hill. She is one of the most well spoken and knowledgeable teens, let alone people, I have met - especially regarding her health conditions. She is always willing to answer questions and help others navigate a very confusing set of diseases.  She developed POTS as a young teen, but then her symptoms changed and became more severe, and she was given a tentative Mito diagnosis after numerous positive tests and working with both Mito and POTS specialists.  

by Hannah

The mitochondria are the “power-plants” of the cell—they provide most of the energy a cell needs to function. There are mitochondria in every single cell except for red blood cells. Mitochondrial disease, or ‘mito’ is a genetic and generally progressive problem with the mitochondria. (There is also a concept of “mitochondrial dysfunction”, where there is no gene mutation but the mitochondria don’t work well because of some outside force, such as certain medications or diseases.) The spectrum of severity of mitochondrial disease varies widely, from a baby with Leigh’s Disease who passes away before his first birthday, to the very serious MNGIE, to a woman who gets excessively fatigued and weak as she ages.

Cells have multiple mitochondrian that power the cell through by converting ADP to ATP.

The genetics of mito are incredibly complex, but basically the take-away point is that they’re nothing like what you would expect for a genetic disease. It can be inherited in any pattern (maternal, autosomal recessive, autosomal dominant, or a spontaneous mutation - otherwise from Mom, Dad, both, or neither), and the severity and symptoms aren’t consistent within families. Symptoms can develop at any age, or people can have a mutation and not exhibit any symptoms.

Because mitochondria are in so many places, when they don’t work well a staggering number of symptoms can arise. Any system can be affected, although the systems that require more energy (brain, GI tract, muscles) tend to have the most issues.

Here’s a list of some common symptoms:
·         Dysautonomia (malfunction/disease of the autonomic nervous system)
·         Seizures
·         Ataxia (a lack of muscle coordination)
·         Muscle weakness or spasticity
·         Stroke-like episodes
·         Developmental delays or autism
·         Ptosis (drooping eye lids)
·         Deafness
·         Motility issues (problems withe food moving through the digestive tract)
·         Trouble swallowing or aspiration
·         Diabetes

“What are the symptoms of Mitochondrial Disease? This is not the question one should ask. Rather, one should ask, in what situation should we consider Mitochondrial Disease? This question I can answer: when a child has multiple symptoms, with multiple organ systems involved, but no unifying answer to it all, it is time to consider mito.”[i] Or, as my POTS doctor says, “when I have a patient with POTS and other issues that are ‘weird’, my mind goes straight to mitochondrial disease.” So, people that have other mystery health issues involving multiple systems should consider adding mito to the list of possible POTS causes.

Mito and POTS                      
Autonomic dysfunction is very clearly a part of mitochondrial disease. Just as any other system can get too little energy, so to can the autonomic nervous system, causing autonomic neuropathy, a subset of peripheral neuropathy.  The Mayo Clinic estimates that 50% of people with POTS have autonomic neuropathy.

Mitochondria shown in the context of a nerve cell/network.

 Here is a published study’s discussion of peripheral neuropathy in mitochondrial disease (by the way, respiratory chain complex deficiency is just a fancy way of saying mitochondrial disease):

 … The results of this and previous reports demonstrate that peripheral neuropathy is a strikingly common and early manifestation of mitochondrial diseases, regardless of underlying genotype, and suggests that a common mechanism underlies this complication. The efficient conversion of substrate fuel (primarily carbohydrate) into energy requires the integrity of both nuclear and mitochondrial genomes, but this process is perturbed in patients with loss-of-function mutations in … the respiratory chain complexes 
We postulate that cellular energy failure is the most likely common cause of peripheral neuropathy in patients with… respiratory chain complex deficiency, regardless of how the neuropathy is manifested clinically or histologically.[ii]
So basically, the cause of autonomic dysfunction is what we assume it would be—the nerve cells aren’t getting enough energy.

Faulty Mitochondria--->Faulty Autonomic Nerves--->
Faulty Autonomic Nervous System--->POTS

Autonomic neuropathy in particular seems to be very prevalent in mito: in a study of 22 patients with mitochondrial disease “ten patients (46%) had definite autonomic damage… eight patients (36%) showed moderate alterations… and four patients (18%) had normal autonomic function”.[iii]

So, if mito is a possibility for someone, how do they get tested?
Unfortunately, mito testing, in a word, sucks. It’s complicated and imprecise. So, there are many people out there (myself included) who have tests pointing to mitochondrial disease, are being treated for mitochondrial disease, but can’t get that official diagnosis yet. Many doctors are very hesitant to hand out the diagnosis unless they’re 100% sure, because mito is very serious.

Here are the testing options:

·         Metabolic labs: a whole lot of bloodwork. This isn’t enough to provide a diagnosis, but if some of the labs are off it can point in the direction of mito. If they’re normal, though, mito isn’t ruled out.
  • Examples of some of the tests include: plasma lactate and pyruvate, plasma acylcarnitine analysis, carnitine, comprehensive metabolic panel, quantitative plasma amino acids, quantitative urine organic acids, and COQ10.

·         Genetic testing: over 1500 genes can cause mitochondrial disease, and they can currently test most, but not all, of them. The problem is, the technology has outpaced our knowledge. Many people have variants found, but they could be disease-causing, or they could just be a fluke. If the results show a mutation known to cause disease, though, that would provide a definite diagnosis.
          Muscle biopsy: For years a surgical muscle biopsy, literally taking a piece of muscle and studying the mitochondria in it, was how everyone was diagnosed. However, they are being moved away from for a few reasons:
o   They are a surgery done under anesthesia, which is unpleasant and carries risks.
o   There are false positives and false negatives.  Many hospitals don't do the muscle biopsy properly or preserve it incorrectly, which totally invalidates it-- in which case it has to be repeated.
o   Biopsies only can tell that the mitochondria aren’t working right, not if it’s the genetically based mitochondrial disease. A person could have mitochondria damaged by medications or even an unknown disease process.
      Buccal swab: New and experimental, this is a cheek swab that looks at some of the things that the biopsy does. Some doctors diagnose off of it, some treat it as a clue like the metabolic labs, and some don’t trust it.

A child's mitochondrial mystery case study found here.
One thing to make clear is that mitochondrial diseases don’t have to have a name. When scouring the Internet, you may have come across names like ‘MELAS’ or ‘MERRF’. The old way of thinking was that each mitochondrial disease had a name and phenotype corresponding to specific mutated genes—but then, once doctors learned that there are 1500 genes that can cause mitochondrial disease, they quickly stopped naming them all. Most people do not have a named disease. Some doctors who are not mito specialists do not know about this change, though, and will only test for the named types—and if that happens, switch doctors to be sure you are thoroughly evaluated.

What is the treatment for mito?
Right now, the main treatment is the “mito cocktail” - a combination of high doses of vitamins to kick-start the mitochondria. The cocktail isn’t miraculous, but may improve energy and slow progression. It is also extremely important to minimize fasting and metabolic stress.

Coming down the pipeline, though, is a drug named EPI-743 that is showing great promise in clinical trials. Huge numbers of scientists are putting their heads together about mitochondrial disease, and big strides in testing and treatment should come along in the next few years.

As you can see, mitochondrial disease is complicated—and I’ve barely scratched the surface.  I don’t know everything, but feel free to comment if you have more questions.

[ii] Peripheral Neuropathy in Genetic Mitochondrial Diseases, Volume 34, Issue 2, February 2006, Pages 127–131.
[iii] Evidence of cardiovascular autonomic impairment in mitochondrial disorders, Journal of Neurology, Volume 254, Number 11 (2007), 1498-1503.

 Other Sources/Resources:
1. Mitochondrial cytopathy in adults: What we know so far. Cleveland Clinic Journal of Medicine vol. 68 7 625-626 
6. Other Support:

One other quick note - while reading up on Mito, I (Claire) learned that it turns out Mito is now implicated in more and more diseases and conditions, so being aware of the symptoms and signs becomes especially important if you suffer from any of these as well as POTS or autonomic dysfunction in general (from UMDF): 
  • Alzheimer’s Dementia, Parkinson’s disease, Huntington Disease, Amyotrophic Lateral Sclerosis (ALS), mental retardation, deafness and blindness, diabetes, obesity, cardiovascular disease and stroke. Over 50 million people in the US suffer from these chronic degenerative disorders. While it cannot yet be said that mitochondrial defects cause these problems, it is clear that mitochondria are involved because their function is measurably disturbed.
  • Even autoimmune diseases such as multiple sclerosis, Sjogrens syndrome, lupus and rheumatoid arthritis appear to have a mitochondrial basis to illness.
  • Mitochondrial dysfunction has been associated with a wide range of solid tumors, proposed to be central to the aging process, and found to be a common factor in the toxicity of a variety of physical and chemical agents.
  • Cancers are also associated with defects in the mitochondria. Within the cell, signaling must occur between the mitochondria and the nucleus. When the signaling malfunctions, the defect can cause cancer.
  • Researchers discovered that mutations in the mitochondrial DNA may play a role in tumor metastasis and suggests a possible new avenue for the development of a treatment to suppress metastasis.
  • Researchers have found a very consistent decline in mitochondrial function that is found in diabetes and pre-diabetes.
  • There is increasing interest in the possibility that mitochondrial dysfunction might play an important role in the etiology of autism. A subset of autistic children have already been shown to manifest biochemical alterations that are commonly associated with mitochondrial disorders, and a few have been linked to specific alterations in the mitochondrial genes. (4)
Also - as a former biology teacher/researcher, I was having flashbacks to cell biology (the citric acid/Krebs cycles) while researching and reading about Mito.  If you are interested in the processes in detail and some cool facts check out this site.  Mitochondria are actually quite unique and interesting organelle's, and insanely important in many ways.  

Thanks again to Hannah for contributing such a great article! 


  1. You're in the Atlanta area? That is THE place for mito... Dr. Kendall (who's fantastic) is there, along with Dr. Shoffner. I would definitely recommend making an appointment with one of them.

  2. Hi, glad someone else is onto this. I ave been chronically ill and fatigued for decades since the age of 8, drs insisting it was anxiety related stomach aches. I've got POTS gluten free diet has cured the stomach ache though. I'm sure it's mito but drs just think you're a hypochondriac if you do your own research. Rest, hydrotherapy and gluten free diet has helped. Looking forward to real research not psychobabble. :) good luck everyone .

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