Dear Dr. (Mitochondria)

Thanks for considering running Mitochondrial Genomic Testing for me.

The Fluoroquinolone (FQ) antibiotics are increasingly suspected of either directly causing (via their genotoxic mechanism of action) or “unmasking” underlying mitochondrial disorders, as stated by the FDA and SONAR here:

The Southern Network on Adverse Reactions (SONAR) Citizen’s Petition

Department of Health and Human Services Public Health Service Food and Drug Administration Center for Drug Evaluation and Research Office of Surveillance and Epidemiology Pharmacovigilance Review

Fluoroquinolones are the only Topoisomerase inhibitors utilized as antibiotics. All other TOPO inhibitors are chemotherapeutic agents, and FQ’s are constantly being studied for their chemotherapeutic properties as well. It is because of their genotoxic mechanism of action, along with mitochondria being presumed natural targets of these drugs, that FQ’s are suspected of directly causing mitochondrial damage or depletion:

Topoisomerase Poisons: Harnessing the Dark Side of Enzyme Mechanism. If you don’t want to read the entire paper, the important points relevant to this topic are summarized here: “The topoisomerase-targeted drugs discussed above work in an insidious fashion. Unlike most enzyme-targeted agents, the compounds shown do not kill cells by blocking topoisomerase catalytic function. Rather they take advantage of the Dr. Jekyll/Mr. Hyde character of topoisomerases (i.e. enzymes that perform essential DNA strand passage reactions but cleave the genetic material) and poison these enzymes by increasing the steady-state concentration of their covalent DNA cleavage complexes. This action converts topoisomerases into physiological toxins that introduce high levels of transient protein-associated breaks in the genome of treated cells . . . Topoisomerase-DNA cleavage complexes are mutagenic in nature. Furthermore, the potential lethality of these drug-induced cleavage complexes rises dramatically when replication machinery or helicases attempt to traverse the covalently bound topoisomerase roadblock in the DNA. Such an action disrupts the cleavage complex and converts transient single- or double-strand breaks into permanent double-stranded fractures which are no longer held together by proteinaceous bridges. Once these untethered breaks are produced in the genetic material, they become targets for recombination and repair pathways. This in turn stimulates sister chromatid exchange, the generation of large insertions and deletions, and the production of chromosomal aberrations and translocations. When these permanent DNA breaks are present at sufficient concentration, they trigger a series of events that ultimately culminates in cell death by necrosis or apoptosis . . . Due to the mechanism of drug action, the higher the physiological concentration of topoisomerases, the more lethal these poisons become . Levels of topoisomerases I and II are generally elevated in cells that are undergoing rapid proliferation. This probably contributes to the increased response of aggressive cancers to topoisomerase-targeted agents.”

I’m supplying this reference paper and information for you because if it is true that mtDNA are being targeted by FQ’s, it seems to me that larger scale insertions and deletions are a real possibility with these drugs. It also seems to me that in theory, if this is actually occurring, then that’s something that may actually show up in testing, given all the symptoms that I have and the fact it’s now been five years since my initial reaction (ie, enough time has passed that replication of potentially defective mitochondria has reached the critical point and may become visible genomically).

Regarding mt/nmtDNA testing, I was looking at this company here, because they do also look at some of the nucDNA that affect mitochondria as well: I’ve been in contact with a rep, and he says they will work extensively with physicians and insurance companies to help expedite the testing.

You asked for a summary of my symptoms. I’ve got some extremely detailed write ups on my symptoms, and have kept records of all of them throughout this entire ordeal. However, they basically fall into the general categories of brain, heart, muscle, connective tissue, endocrine, and eyes for me. Brief outline of symptoms include:

  • Muscle weakness, fatigue, and tremors. I can no longer go on walks outside, except to my mailbox. A “lactic acid” type buildup of pain exists in my thighs all the time. Walking too much makes these symptoms worse, including severe neuropathy (“electric fence, shocks, buzzing, burning” feeling in thighs).
  • Extreme general fatigue all the time, worsened with any type of “exercise”.
  • Peripheral neuropathies – especially of face, feet and legs, but can occur throughout entire body. In extreme cases, I feel like my finger is stuck in an electric socket, with a “whole body buzzing”, or “just” my face and head, including my tongue, which will also feel “thick” and “numb” and makes swallowing difficult.
  • CNS symptoms – these are ongoing, and basically feel like some kind of encephalopathy. Severe pain, disorientation, “brain fog”, mood swings, “head pressure”, trigeminal and geniculate neuralgia type pain in face and ears (tinnitus, pain, ear hearing changes); difficulty reading, writing, and comprehension at times due to these symptoms; the disorientation causes balance issues.
  • Cardiac issues: arrhythmias, tachycardias, palpitations, pounding heart beat, chest pain. A cardiac workup ruled out cardiac issues despite this. I’m pretty sure the chest pain I’ve been experiencing, which is progressing, is actually thymus related. At times, pain is severe, with sweating/hot flashing, and I feel like I’m having a heart attack (but apparently, I’m not). Cardiac arrhythmias are highly thyroid hormone and iodine responsive but within an extremely narrow therapeutic range: a few micrograms of either in either direction brings on these cardiac symptoms and it’s difficult to maintain any sort of homeostasis.
  • Ocular – very painful eye muscles, eye fatigue, blurry vision, dry eyes, disorientation (feels like my eyes move a tad behind my brain, hard to describe, but it’s very disorienting). My eyes have been a constant problem and complaint for me since this began, and this is a big reason I suspect Ocular/MuSK MG (Myasthenia Gravis), and now, possibly a mitochondrial issue as well.
  • Endocrine – The one definite diagnosis I have is Hashimoto’s Thyroiditis. I have a sensitivity to all steroid hormones now, including thyroid hormone (appears to exacerbate my MG-like symptoms, including thyroid gland and thymus pain and swelling). I also have glucose abnormalities (essentially Type 2 Diabetes). I think Hashi’s Encephalopathy should be on the list, despite the fact my antibody titers are considered “moderate”.
  • Additional: Extreme food sensitivities (suspect glutamate, glutamine, glutamic acid is a big one, along with micrograms of iodine, which definitely is a problem). I can hardly eat anything anymore without making all these symptoms worse. I still have generalized tendon pain, hair loss, dry skin, deteriorating teeth and painful teeth when head is extremely neurological; phantosmia, nausea and stomach pain, and disorientation and balance problems, including vertigo. I think this covers the basics, although I’m sure I’m forgetting some things.

I understand that Mitochondrial Genome testing is in its infancy, and fraught with diagnostic challenges. Despite this, more and more it is being used clinically and successfully for helping to diagnose and verify challenging conditions. There are FQ victims who have been diagnosed with “Mitochondrial Disease” post flox by physicians willing to test for this,although I’m not sure by what criteria. So I think it may be a possibility in my case as well.

Again, thank you for your interest and consideration, I greatly appreciate it.

Sincerely,

Flox victim