Ask the Mito Doc – December 2022: Q&A: What to Expect as an Adult Mito Patient

Ask the Mito Doc – December 2022

What to Expect as an Adult Mito Patient


Clinician: Dr. Michio Hirano, MD of Columbia University Irving Medical Center in New York, NY


Watch the video:

Ask The Mito Doc: December 2022 – What to Expect as an Adult Mitochondrial Disease Patient – YouTube


Q: I was told about a year ago by someone in the group to try my BIPAP during the daytime as soon as I feel a “crash/ decompensation/stroke like event” coming on. I quickly learned that for me, I also had more energy after using it for a while during the daytime, so now use it when need a little more energy in daytime. Not sure why Is this usual for others too?  

A: Many patients with mitochondrial disease have weakness of respiratory muscles that can be treated effectively with BiPAP, a non-invasive form of ventilation. Many patients benefit from nighttime use but also intermittent use during the day. It is best to consult a pulmonologist for guidance on BiPAP use.


Q: I have a growing issue with neuropathy. Sometimes in a specific area, and sometimes, all over my body. Are there treatments or suggestions to relieve this? I currently take gabapentin.

A: Gabapentin, pregabalin, and amitriptyline are commonly used to treat neuropathic pain.


Q: I have adult-onset mitochondrial disease. I was told I have replications and deletions in my mitochondrial DNA. I also have been diagnosed with 3 autoimmune diseases: Sarcoidosis, Mastocytosis and Psoriasis. My question… Can mitochondrial diseases cause autoimmune diseases?

A: There is growing evidence that mitochondrial disease affects the immune system and vice versa. For example, autoimmune myopathies such as inclusion body myositis cause secondary mitochondrial DNA deletions and ragged-red fibers. That said, I am not aware of any primary mitochondrial diseases that cause autoimmune disease.


Q: We have not found many adult Mito providers, rather many pediatric Mito providers will continue to see their patients into and through adulthood. What are the benefits/challenges to either staying with a pediatric provider as an adult or moving to a adult provider, in terms of medical care for adults with Mito myopathy?

A: I think there are probably more pediatric doctors who treat mitochondrial disease at this moment than for adults. So there seems to be a big shortage, a great shortage of adult physicians for our young people who are transitioning into adulthood and for our adult patients in general. I think you could start with your current team of pediatricians and pediatric mitochondrial specialists, since they know the community that they serve, and they can probably refer you to someone locally. But that’s not always possible. And if there’s not an adult counterpart for that pediatrician in that particular hospital system you may have to look elsewhere.

And looking at resources like The UMDF can sometimes help, and certainly there is the NAMDC North American Mitochondrial Disease Consortium, which has sites around the country as well as the Mitochondrial Medicine Society.

An adult primary care physician can contact UMDF and Mito U that is where there is a host of courses.


Q: What treatments or supportive therapies are recommended for adults with mito who have diaphragm weakness, specifically low MIPs/MEPS? Is treatment any different because of a mito diagnosis? And, are there any treatments that are contraindicated because of mito?

A: Patients with mitochondrial disease often have exercise intolerance out of proportion to weakness. You may look normal, and you may have pretty good strength, but you poop out quickly.

This not only affects the limb muscles, but respiratory muscles, so diaphragm and intercostal muscles can be weak, and this causes restrictive lung disease. It’s what the polynomial is but also build our muscles. Chronic, progressive GI issues are common, but also swallowing muscles oral pharyngeal muscles can be affected, and that’s an important risk in a surgical procedure, any procedure. Because if you have trouble swallowing, you’re a greater risk for aspiration and aspiration pneumonia so that needs to be considered in surgery. Another risk may be of decreased mobility increases the risk of blood clots, deep vein, thrombosis in the legs. So, you have to prophylactically treat the patient.


Q: With what is now known… Specifically, what are the links between mitochondrial diseases and age-related diseases E.G.: heart disease; diabetes; cancer; Parkinson’s & Alzheimer’s disease? Has data shown certain types of mito-diseases are more prone to developing age-related diseases, and if so, which types and why vs other types of mito-diseases?

A: There are a number of connections between Parkinson’s disease or Parkinsonism. There is the classic sporadic onset of the disease another cause can be trauma to the brain. There are also early reports of Complex 1 deficiencies in these patients that can be detected in the blood. So, there are multiple lines of evidence, indirect, suggesting these links. And then there’s these rare genetic forms of Parkinson’s disease that due to mutations in alpha- synuclein, PARK and PINK1, and I won’t go through the mechanism. But just say that they’re all the proteins associated with mitochondrial functions, again, and implicating mitochondria in the pathway of Parkinson’s disease, and Parkinsonism.

Q:Can a person with an SMA Spinal Muscular atrophy gene mutation or carrier but does not have SMA still have a Mito disease? 

A: There are rare cases of mitochondrial diseases that mimic SMA. The best example is thymidine kinase 2 deficiency.


Q: Is there any chance you broadening your target population in trials now available or in the future?

A: Clinical trials usually focus on target populations that are most likely to show clinically important benefits from a particular therapy. It is possible that the target population can be broadened later.


Q: My doctor suspects MNGIE. What tests should be conducted to determine if I have MNGIE?

A: Genetic testing for TYMP gene mutations confirm MNGIE; however, if the genetic test result is ambiguous, then measurement of thymidine phosphorylase activity or levels of thymidine and deoxyuridine in blood can definitively confirm the diagnosis.


Q: Are there any new developments in treatment options of MNGIE disease?

A: Liver transplantation is emerging as a treatment for MNGIE and seems to be safer than bone marrow transplants.


Q: Is there a connection between nerve pain, and mito? Can it improve?

A: Painful peripheral neuropathy is frequent in mitochondrial disease. I previously listed some medications that can be used to ameliorate the pain.


Q: Is there a way for an adult patient to easy the daily fatigue after doing regular daily things? The fatigue is debilitating resulting in lots of pain. Muscle pain and weakness.

A: Chronic fatigue is very common with mitochondrial disease. Aerobic exercise, such as bicycling or swimming for up 30 min every other day, can be beneficial in improving exercise capacity, increasing the number of mitochondria kind of like making ragged red fibers in the muscle by increasing the number of mitochondria. It can improve your quality of life. If you can’t do 30 min of exercise. Maybe 5 min of exercise every other day is a better target. Initially, when you’re starting out. You don’t want to hurt yourself, and I generally tell people if they’re achy for a couple of days afterwards, and they’re in bed, obviously they’ve overdone it. So you have to titrate your exercise when you do that. Another way to look is check your blood CK, is an enzyme that’s in the muscle, and when you damage your muscle, leaks out so you can measure your CK before and after exercise, and it goes way up. You’ve probably overdone it. You’ve damaged your muscle.


Q: What have we learned about the Mito community and Covid? I am wiped out by having had Covid after 5 months.

A: An Italian study showed that mitochondrial disease patients are not necessarily more severely affected by Covid than the general population. Unfortunately, long Covid occurs frequently and will worsen the baseline fatigue of mitochondrial disease patients.


Q: Besides exercise is there any diet or foods that can help people with major fatigue issues? Maybe you can comment on mito cocktails supplements that may help some people, and do they help people suffering from infection more than gene mutations?

A: Mitochondrial cocktails and supplements are taking by many patients. Many patients find them beneficial.


Q: Are Mito conditions recognized by most doctors? My primary care doctor didn’t want to explore the possibility.

A: Unfortunately, many doctors are not familiar with mitochondrial diseases. You can tell your primary care doctor about MitoU.


Q: Are mitochondrial cocktails helpful? If so, do you have any recommendations?

A: I’ll give you a brief answer, and then a more detailed. The first answer is, you know, if you ask 10 different mitochondrial disease experts about supplement cocktails that they use, you probably get 10 different answers. There is no clear single consensus about the cocktail, and what should be in it. Nevertheless, you know, surveys of patients indicate that they feel that the cocktails are beneficial.

There is some benefit to taking cocktails it’s very hard to know how much of it is, is, due to the particular, a particular supplement, or a combination of supplements, because we haven’t done clinical trials. And there’s also the possibility that there’s a placebo effect as well. So, this is an area where we would love to have clinical trials and data, so we can give you more scientific answers. But for now, we can say that supplements do seem to help the people in some way, and I think you’ll have to work with your mitochondrial disease expert and try to find a combination that may work for you.


Q: What is the probability of stomach and intestinal involvement in TK2 deficiency disease? If there is such an example, has our current drug treatment, which is still being studied, an answer to this involvement in these patients?

A: TK2 deficiency is rare. Myopathy predominantly so. It affects limb muscles, and respiratory muscles early, so often patients have respiratory issues. The GI system can be affected as well.  Patients sometimes have nausea, vomiting, diarrhea, constipation, and GI dysmotility issues that we covered earlier. It’s not very common, and it’s complicated by one of the medications we’re trying. Now this, nucleoside therapy which can in high doses cause diarrhea. It’s both a problem of the disease sometimes and frequently a problem of experimental therapy that’s in a clinical trial.


Q: Is the Dec 20th 2022 UMDF event about clinical trials only for providers?

A: Anyone can attend! Yes, so it’s very exciting for us. The pharmaceutical industry is now interested in mitochondrial diseases. Previously we thought that they were so rare that the pharmaceutical companies wouldn’t be interested in developing drugs, but they are, and we are very fortunate now. The several companies have been involved with a variety of mitochondrial diseases, and most of these trials are targeting patients with primary mitochondrial myopathy.

The UMDF website has a list of clinical trials. You can look up these clinical trials and find one that might be suitable for you.


Q: Are epileptic seizures the only seizures associated with Mito? And can you go over the Valproic Acid again? I was prescribed it as an emergency migraine cocktail, and it went horribly wrong. We thought it was an allergic reaction, but I’m wondering if it’s something else pointing to mito.

A: There can be interactions with anti-seizure medications and anesthesia. Valproic acid is often used as an anti-epileptic drug. They certainly can reduce seizure frequencies, however, in one mitochondrial disease, Alpers Disease, which is caused by POLG1, medications with Valproic acid, can cause severe liver disease hepatitis which can be fatal. In this situation it’s an absolute No, to take Valproic acid. And we know that sometimes about Valproic Acid, it can be toxic, to the liver in general, perhaps in heart disease, patients more so, but particularly with the Alpers patients. We generally try to avoid prolonged use for patients with mitochondrial disease. But occasionally, when we’re, you know, faced with patients with seizures that are very difficult to try and control. We sometimes must use valproic acid.


Q: Why should metformin be avoided in mito patients with diabetes?

A: Metformin is probably the most prescribed medication for diabetes after insulin, It’s a very effective drug. Unfortunately, metformin can be toxic to mitochondria by blocking complex one. Therefore, we try to avoid using metformin, in patients with a mitochondrial disease, and particularly those with kidney dysfunction or a kidney disease. Metformin is maybe more toxic in that setting. Occasionally we use it. There are many new diabetes drugs that can be used as alternative.


Q: Are any specific mitochondrial diseases associated with Chronic Intestinal Pseudo Obstruction?

A: Patients with Mito often have dysmotility issues. Patients have problems with diarrhea, constipation, abdominal bloating after eating, early satiety, you eat a little bit of food, and you get full very quickly, because the stomach does not empty quickly. Esophageal dysmotility. Food gets stuck in your throat, swallowing difficulties in the oropharynx. They’re all part of this gastrointestinal dysmotility spectrum particularly in MNGIE but in MELAS it may be subclinical, meaning you may not even know that it’s there. But during surgery it may be unmasked. Surgery often worsens it. The anesthesia can worsen the problem where the intestinal system doesn’t contract as well, and you get paresis or nausea, vomiting, gastroparesis. So, the motility issues can get worse. And even in normal people there’s some problems with gastro-motility. Recommend seeing a Gastroenterologist before surgery.