Journal of IiME Volume 2 Issue 1 www.investinme.org M MEE//CCFFSS aass aa MMii ttoocchhoonnddrriiaall DDiisseeaassee ((ccoonnttiinnuueedd)) storage chemical (battery) of the body, and oxidative phosphorylation (ox-phos) the complex electron transport chains that do the major work. Because the mechanism of energy production is essential to nearly every cell, a defect will have symptoms in every organ system. Sound familiar? Oxidative metabolism, the ability to utilize oxygen to produce energy, is quite efficient, and it is fascinating to look at the theories of how they came to be part of our cells. However, when the energy demand is excessive, the cells revert to a more primitive, and less efficient, form of energy production, anaerobic metabolism (metabolism without oxygen). For an interesting study on the anaerobic threshold in ME/CFS, see the literature review article that follows. When to suspect mitochondrial disease. In a recent review article (Haas 2007) there is a list of symptoms that suggest looking for mitochondrial disease. Among these symptoms are neurologic symptoms such as ataxia, myoclonus, and encephalopathy, exercise intolerance, sensitivity to general anesthesia, and constipation. A score sheet has been developed to help in when to suspect mitochondrial disease and most ME/CFS patients would fall into the positive range. For lots of information on mitochondria please go to www.mitosoc.org, but remember that they are talking about “conventional” mitochondrial disorders, not ME/CFS. There is another form of mitochondrial disease, or secondary mitochondrial disease. In secondary mitochondrial disease the primary problem is not with the mitochondria, but some other problem messes up mitochondrial function. There are many illnesses where the primary defect ends up causing problems with the generation of energy in mitochondria. For example, thyroid hormone is needed for successful oxidative phosphorylation. With hypothyroidism (low thyroid) energy production is impaired and fatigue, weakness, temperature regulatory problems, and difficulty concentrating result. This is one of the reasons that when you start to describe fatigue to your primary care physician, he or she begins to write out a script to test for thyroid hormone. So what is the problem? Why has ME/CFS not been diagnosed, studied and classified as other mitochondrial diseases? There are several reasons: a) Mitochondrial disease is thought of by clinicians as a fatal disease of infancy, not one that occurs later in life. b) Mitochondrial disease is usually thought of as a fixed, structural disease, and ME/CFS is a relapsing, remitting illness with some persons even becoming entirely well. c) Mitochondrial diseases are hard to diagnose, requiring muscle biopsies and detailed ox-phos testing d) Ox-phos testing is often normal in ME/CFS, and this Invest in ME (Charity Nr. 1114035) Page 21/34 has been the critical piece that has diverted attention from mitochondria. e) Physicians are used to thinking of organ-specific diseases (liver, kidney, etc) and mitochondria are in all cells. f) Few physicians have taken ME/CFS seriously until recently, and research in this area has been scant. Of the above reasons, only reason “d” is important to us here. In 1990 I did a muscle biopsy study on ten ME/CFS patients with Dr. June Aprille. All ten persons had relatively normal ox-phos studies. Although we did not publish this finding, it is consistent with the few published studies that have been done. How can you have mitochondrial disease when the mechanism tests normal? I think that the answer to this paradox is just around the corner. Hypothesis: If you have a patient with emphysema who is sitting in an armchair, he or she is not out of breath. You can measure the damage in tests, but to make symptoms, you have to “stress” the system – make the patient run up and down stairs. If a person with G-6-PD deficiency is sitting quietly, the blood looks normal. But feed this person fava beans and abnormalities quickly become obvious. Persons with ME/CFS keep themselves at a balance point. They rest for two hours, then do a half hour of activity, then rest, then do more and so on. The worse the illness, the less overall activity is possible. If a ME/CFS patient does absolutely nothing for a few days, they usually feel pretty good. But go to the shopping mall for eight hours and the crash occurs. Here is the problem: in the patients studied for mitochondrial disease, they have been resting up (staying above the balance point) and a muscle biopsy done at that moment will probably not show much. But have a ME/CFS patient exercise, and then study mitochondrial function. My hunch is that the ox-phos reactions will be seriously impaired, but this has not been systematically and methodically done. For me, this hypothesis is generated by the VanNess, Snell, and Stevens study described in the next section. There are lots of studies that implicate mitochondrial problems; Dr. Kuratsune and carnitine. Dr. Versnon and genomics; Dr. DeMeileir, Dr. Pall, Dr. Cheney and many others. But this problem cannot be studied in tiny fragments. It is time for a good study to look at the different steps of the body’s ability to generate energy. Lets hope we get to see it within our lifetimes. 1. Haas R, Parikh S, Falk M, Saneto R, Wolf N, Darin N, et al. Mitochondrial Disease: A practical approach for primary care physicians. Pediatrics 2007;120(6):13261333 (Continued on page 22)

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