Hey friends,
I’m sorry it’s taken me so long to write an update on how my neurometabolic appointment in San Diego went!
Been trying to pull all my thoughts together on what we learned at the appointment.
After updating my mito dr. on all that’s happened since I last saw him, he is thinking more and more that the POLG gene variant that was found in my whole exome sequencing is the likely culprit that’s causing my mitochondrial DNA depletion.
According to the NIH genetic reference site, POLG “is a DNA polymerase, which is a type of enzyme that “reads” sequences of DNA and uses them as templates to produce new DNA.” It is also the “ only DNA polymerase that is active in mitochondria and that can replicate (make new) mtDNA.”
Again, he said I’m very special and that he’s never had a patient with mtDNA depletion syndrome AND Wilson’s Disease. So he wants me enrolled in the North American Mitochondrial Disease Consortium…currently, there are about 1200+ patients enrolled. It’s hard to explain what NAMDC is, so you can read all about it here: https://www.rarediseasesnetwork.org/cms/namdc/About-Us
Please read the link! It’s very helpful to understand.
POLG-related mitochondrial diseases can cause numerous issues, including problems like cardiomyopathy. So he said I need to have an EKG every year and an echocardiogram every 2 years. I also need to stay away from certain medications that can induce POLG-related liver failure.
There is a drug trial that is in phase 3 and going well, but this medication (called Elamipretide) is mainly for mitochondrial myopathy, so he said that wouldn’t be the best fit for me since I have more issues than just muscle weakness. He did say the company that created Elamipretide is starting to work on many other promising drugs.
One of the main things we learned from this appointment is that things take TIME. It takes time for companies to make new drugs….time for drug trials to “pass” through all the phases and get FDA-approved….time for research to discover new mitochondrial pathogenic (disease-causing) mutations and whether variants of uncertain significance (VUS) that are found through whole exome sequencing are pathogenic or not….and much more..
My POLG gene variant is a VUS, and in order for it to be “confirmed” as pathogenic, there are 2 ways that can happen. If you put this specific variant in animal models (like mice) and they develop the same symptoms as the patient, then that variant gets labeled as “pathogenic.” But….this route takes a ton of money to do.
The other way to confirm a VUS as pathogenic is to put a patients’ genetic data/reported phenotype in a database like NAMDC or MSeqDR (Mitochondrial Disease Sequence Data Resource Consortium), and if several patients with the same variant have similar symptoms, then that variant gets confirmed as pathogenic.
So it’s enouraging to hear all that’s being done in the mitochondrial disease world, but it’s also hard knowing that everything takes SO long to happen/do.
I asked him what my future will look like medically, and he said no one can really say (since every patient with mito presents differently)….he said mito is very serious, but he also told me that I’m coping really well. Of note, he did say my brainstem is not functioning well…. The “sleep center” is in the brainstem which is why my complex sleep apnea is so bad.
Regarding my myoclonus, the medication I’m on for that isn’t helping the best, so he told me about another medication I could try that doesn’t worsen apnea. I have to see my neurologist here to talk about it.
I wasn’t able to make it to this year’s United Mitochondrial Disease Foundation (UMDF) national symposium because it was in Nashville. My mito dr. said he was looking for me there. Next year’s is again going to be on the East coast, but my dr. told me that the UMDF symposium in 2020 will probably be in San Diego!
Looking forward to that! It’s so encouraging to see how dedicated/invested my dr. is in all things mito-related. He really cares for his patients!
In other news, I saw my physical medicine dr. recently, and he wants to make sure my osteopenia (soft bones) doesn’t progress. It’s not good to have at my age, so he referred me to OHSU’s endocrinology/bone metabolism clinic. Another dr. to add to my long list of specialists.. The clinic is booked out, so my appointment isn’t until September.
My hip surgery is scheduled for August 10th. Less than 2 1/2 weeks away! The surgery scheduler is working on setting up my pre-op appointments as well.
I saw my GI dr. today, and he wants me to try another medication for my GI dysmotility. It’s been bad lately. Will be starting at a low dose first. Because my vitamin D level was low despite taking 5000 IU daily, I now have to take 50,000 IU (prescription strength) since low vitamin D is bad for osteopenia. In addition, my GI dr. wants me to start taking a vitamin A beta carotene supplement (25,000 IU) because my carotene blood level was very low as well. He’s also going to get in touch with my general surgeon to have my j-tube changed during my hip surgery.
I hope this update about my San Diego appointment was easy to understand. Mito is so complex which makes everything hard to explain.. :/ If you ever have any questions, feel free to comment or send me a message!