Question: I know that some mitochondrial diseases can be somewhat controlled with diet and exercise. What kind of diet do you recommend for a mitochondrial patient with exercise intolerance and gastroparesis, and what kind of physical activity is good for someone with severe exercise intolerance with easy muscle fatigability and immediate anaerobic metabolism?

Answer: The answer is complex and VERY individual - firstly, gastroparesis limits the food intake and the degrees of this are huge (mild >> severe) so keep that in context and you may have to try different types, volumes and timing - in general, it is best to start with some resistance type exercise with 2 days rest between sessions and use a circuit set with 1 set of 15 repetitions - gradually move up to 3 sets of 12 - 15 repetitions and try taking only one day between sessions - after a few months, titrate in short periods of endurance exercise (whatever you like) for only 5 minutes and gradually increase as tolerated to a max of 45 minutes on the day between the resistance/weight sessions. In general 1.2 g protein/kg/d in diet and taking some carbohydrate and protein (10 grams) after a work out is best - of course these are general suggestions and it will likely take a combination of a nutritionist/dietician and a personal trainer/kinesiologist to help with the specifics while you "listen to your body" and do not exercise on days that you have a fever or other illness. Again, these are very general because I do not know you as a patient, but should help.

Question: I was recently diagnosed with adult Mito Disease. I feel nauseous constantly and just feel ill and fatigued all the time. At one point my ck values were very high and my doc thought I was a bit dehydrated so she put me in the hospital overnight with IV fluids. I cannot tell you how much better I felt the next day by noon when they discharged me. I was EUPHORIC I felt so wonderful--like I used to feel before I got sick with the Mito (2 years before of constantly feeling horrible). I rushed home and called my family so excited about how great I felt and I thought that maybe the idea would be for me just to drink water ALL DAY LONG to try and simulate what I got in the hospital. To my dismay however, no matter how much water I drank and drank and drank within 24-36 hours I was back to feeling terrible again. That was one of the worst setbacks I have ever encountered-to have a brief "taste" of feeling like my old self again and then it goes away.

My question is this and I know it sounds outrageous, but could I somehow not be absorbing liquids and that’s why I am so sick and nauseous and why the IV made me feel SO much better? Could I be hooked up to IV at home while I sleep? Is that a crazy question to ask? I am too embarrassed to ask my doctor, but at this point I would walk around with an IV 24/7 if it made me feel that good again! As far as I know there was just water in the IV.

Answer: Many people feel better while receiving IV fluids, especially fluids containing dextrose (sugars) and vitamins. Unfortunately, the risks associated with IV fluids are not negligible and therefore it is not something that is typically given outside the hospital. Your response does however seem extreme and may warrant further investigation. Your doctor can check lab work and urine studies to see if you are dehydrated and/or having difficulty absorbing fluid. You should also check with your doctor to see if there were any additives to the fluids you received. You may have an undetected vitamin deficiency that was being treated, or if the fluids contained sugar, you might benefit from increasing your carbohydrate intake and/or supplementing your diet with a long-acting carbohydrate such as corn starch.

Answered by: Mary Kay Koenig, MD

Question: For an acute infection, the doctor gave me a different antibiotic that is new to me; Levofloxacin. I am careful to read the medication guide for it and it has me nervous that someone with Mito should not be taking this. Can you tell me if I am at any more risk than those without Mito in taking this medicine. I am supposed to take it for 5 days and have heard that it is very strong. It may be what I need to get over the infection, but will it have a bad effect on my good mitochondria?

Answer: I think it is important to remember that ALL medications have side effects and not every patient will have some or all side effects published. The fluoroquinolones are used most often in gram negative infections (for example, which usually happens with bladder infections). They represent an important antibiotic family that is used quite frequently, more in the adult world but also in children now. Unfortunately, there are many side effects that have been reported with this class of antibiotic. The usual mechanism of antibiotic selection is to use a broad spectrum antibiotic until the bacteria sensitivities are known and then narrow down the antibiotic selection to the one that is most efficacious against that particular bacteria causing the infection.

The fluoroquinolones have a tendency to decrease pyrimidine synthesis, alter collagen synthesis in Beagles, alter redox-cycling oxygen activation, and can alter bacteria flora (which may induce a specific bacterial infection in the GI tract). There are many other side effects noted, if you read the package insert. The effect on pyrimidine synthesis would be theoretically problematic in a patient with mitochondrial DNA depletion syndrome and possibly severe complex I or II deficiency. The alteration of redox-cycling oxygen activation would be theoretically important in a patient with Friedreich Ataxia where iron overload is a concern. In my patient population I see some patients develop C. difficile infections of the GI tract, but certainly not all. There are assorted other side effects, but most are self-limited.

It is difficult to tell you about a certain antibiotic without knowing the type of mitochondrial disease, how involved your disease might be, and the reason for taking the antibiotic medication. There is always a risk-benefit issue with any medication and medical procedure and one has to weigh what is known about the risks to the possible benefits of the medication. One also needs to understand how and if there is a specific mitochondrial alteration that may take place, given the type of mitochondrial disease.

Answered by: Russell Saneto, DO, PhD, Seattle Children’s Hospital

Question: Our son, age 12, was diagnosed with mitochondria Complex I,II, IV at 12 months. He has low tone, amblyopia, and presents deficits in speech, language, fine motor, bowel control, and cognitive and tests within mental retardation ranges at school. He is currently taking methylphenidate ER 20 mg for attention deficit. There has been slight improvement with the medications but still requires CONSTANT re-direction or one-on-one attention with all activities. We are considering increasing his dosage, but cautious due to side effects. What treatments other than the traditional ADD medications are necessary and/or appropriate in the background of mitochondrial disease? How much does the mitochondrial disease cause symptoms that mimic ADD? Based on his 5 ft, 91 lbs, would you recommend an increase in dosage? Or even changing his prescription?

Answer: The decision to medicate a child with ADD/ADHD spectrum issues is a difficult one and is not typically something I do or recommend unless all other avenues of treatment such as educational modification with, for example, one-on-one teaching assistance has been tried. If all other avenues fail and the ability to learn is severely impacted in a child who has the capacity to do so but cannot, due to ADD/ADHD, then I am supportive of ADD/ADHD medication. Methylphenidate ER 20 mg per day is often a starting dose for this medication. However, modification of current dosage or the decision to switch to another medication must be determined by a treating physician who will weigh the risks and benefits of doing so.

Answered by: Fran D. Kendall, MD

Question: Is there any dietary intervention for patients with mito (and suspected mito, specifically elevated lactic acid and pyruvic acid) that can help to improve symptoms? With our daughter, almost 3 yrs. old, we have found that her body cannot tolerate salicylate-containing foods and phenolic-containing foods (fruits and vegetables and even artificial colors), in addition to severe milk and soy and chemical sensitivities. Since it is well known that as aspirin (acetylsalicylic acid) is metabolized it inhibits COXII and uncouples oxidative phosphorylation, isn't it possible that those who are already mito-compromised, could be negatively affected by ingesting and metabolizing salicylate- containing foods?

Answer: I am not aware that small amounts of salicylate-like compounds in food are in any way harmful but if there are foods that one is sensitive to, avoid them. From a dietary intervention perspective, some find that smaller more frequent meals help. Of course there is a large body of literature regarding supplements that may enhance function.

Answered by: Mark Tarnopolsky, MD, PhD, FRCP(C)

Question: I am a 32 year old identical twin and I was diagnosed with mitochondrial disease (MNGIE) this past May. I am on 100% nutrition with a j-tube and use a power wheelchair to get around. I also have seizures, extreme fatigue, RA, hypothyroidism, adrenal insufficiency, ptosis, chronic progressive external ophthalmoplegia (CPEO), PFO, and an enlarged descending aorta and swallowing/aspiration issues. My identical twin sister has none of these symptoms except the horrible fatigue and has a tremor/shaking in her hands that's cause is unknown. My question is why would identical twins not have the exact same symptoms? Wouldn't we have the same mtDNA mutation and thus the same symptoms? She is extremely worried that she will end up like me. What are the chances of that happening to her?

Answer: MNGIE is a mitochondrial disease that results in all cases from mutations in a nuclear-encoded gene, TYMP (thymidine phosphorylase). A marker for the disease is an increased plasma thymidine concentration, and thymidine phosphorylase enzyme activity in white blood cells of affected patients is below ten percent of healthy controls. This disease is inherited in all cases in an autosomal recessive fashion, which means that an affected individual has disease-causing mutations in both of their copies of the TYMP gene. These mutations are typically inherited from their asymptomatic carrier parents, where two carriers together have a 1 in 4 (25 percent) likelihood of each child inheriting both mutant copies of the gene (alleles) and being affected with the disorder. It is important to confirm that you do indeed have MNGIE, which is best done by sequencing the TYMP gene in your blood to confirm you have two disease-causing mutations. Once the diagnosis is confirmed in you, your sister can then be tested to see if she has the same two TYMP gene mutations that you have. If she does not, it is possible that while she seems to look just like you that she is actually a fraternal (not identical) twin, as not uncommonly is the case. If she does, then it is not uncommon for there to be variation in MNGIE patients regarding the order of symptoms and the age at which they begin. However, should your testing reveal that you do not have MNGIE, then it will be worth pursuing the specific genetic cause for your suspected mitochondrial disease, since there are many different genetic disorders that can have similar symptoms and it would be important to clarify exactly what is the cause of your disease to better understand your own prognosis, therapeutic options, and familial recurrence risk. For example, a mutation or deletion in the mitochondrial DNA genome could certainly be the cause of multi-systemic mitochondrial disease in an adult, where variable heteroplasmy loads of that mutation could account for variable symptoms between family members.

Answered by: Marni J. Falk, MD, The Children's Hospital of Philadelphia

Question:  I have just had cancer surgery and now the oncologist recommends follow-up radiation therapy. I understand that radiation is not good for mito patients, that radiation causes fatigue even in non-mito patients. The oncologist explained that the fatigue caused by radiation is due to cytokines that are generated by the treatment. Are these cytokines mito-toxic?

Answer:  I am sorry that you’re having to go through this tough time. I think you have to look at the long term picture, the use of radiation (given the protocols used to treat cancer) are likely beneficial for cancer control. The benefit here is longer and better quality of life, the risk is that radiation can do damage, not only to mitochondria but healthy cells in the area of the former cancer. I do not believe that cytokines have been absolutely proven to be mito-toxic but there is circumstantial evidence (viral illness inducing mitochondrial disease exacerbation) that they might be toxic. There is some recent evidence that certain medications can reduce the effects of tumor/cancer on energy levels but I do not think this has been translated to mitochondrial disease patients. I would take the benefit approach to radiation treatment and try to do the best in limiting the side effects of radiation. The outlook on your future, your mindset can make a big difference in outcome. One of my college professors, Dr. Norman Cousins at UCLA had cancer and his outlook and use of comedy films (especially the Marx Brothers movies) were his stable and he thought improved his outcome.

Answered by: Russell Saneto, DO, PhD

Question:  I am 49 years old. I was diagnosed with mitochondrial myopathy 5 years ago, although I have had symptoms for 21 years. My balance has gotten worse to the point I must use a cane. I had some tests that showed the vertigo was coming from my Central Nervous System. I also have some hearing loss, kidney failure (lost one kidney to cancer some years ago), sleep apnea, seizures and increased BP and pulse rate. Many of these symptoms started very recently. Can these symptoms be attributed to worsening mitochondrial disease? What do you suggest I do?

Answer:  All of the symptoms you are describing are symptoms commonly seen in people with mitochondrial disease and unfortunately, most adult patients do tend to have worsening of their symptoms over time. My recommendation to you would be to do everything possible to optimize your health status. A good “check-up” at the PCP can go a long way towards improving how you feel. In your case specifically, make sure to control your seizures, have a sleep study and/or use CPAP to improve sleep quality, and see a cardiologist to assess your elevated blood pressure and heart rate. Additionally, I would suggest seeing a physical therapist to help you develop a safe, low-intensity exercise plan. Studies have shown that routine exercise can improve quality of life in people with mitochondrial disease. Lastly, ensure that you are taking adequate doses of CoEnzyme Q10. Although not proven effective, most people with mitochondrial disease describe benefits in energy levels with it.

Answered by: Mary Kay Koenig, MD

Question:  I am a 43 year-old mail with LHON since age 17. My gene mutation is 11178. I've read on the LHON Yahoo Group email list that there is an "avoid list" of medications and substances that should be avoided by people with LHON. However, before sharing this list with my family doctor I would like to source it to a scholarly academic or scientific source. I've always been cautious about obtaining medical advice from non-doctors on the internet. Can you guide me to a source for such a list. I'm also concerned about knowing the underlying chemicals or substances that should be avoided and not just the brand name medications since different medications can all share common ingredients.

Answer:  For LHON, alcohol and tobacco (smoking) are the 2 specific triggering compounds; if all a person has is LHON, there is no need to follow other mitochondrial precautions strictly.

Answered by:  Sumit Parikh, MD

Question:  I have a problem with oxygen processing and passing it on to the other cells needing it, a problem with ATP generation and on THREE major muscle biopsies they found red ragged fibers (RRF) on all three. Is it safe to assume these are related to the other mitochondrial issues? My cognitive abilities, endurance, cramps, stiffness and temp regulation have really increased 10 fold in the last six years and I am 48 year old man. I can no longer mow and if I vacuum I can only do one room. I have abdominal issues with heat or exercise and have had two cataracts removed. I can't stand to sit, stand or do anything for any extended period even though I try. I am perplexed by the RRF and the possible arachnoid cyst at the base of the neck. SSD has turned me down and I cannot get a job after 30 long years of working my tail off. I wanted to see if you had other input on the RRF and etc. I do have sleep disorders and Idiopathic Hypersomulance and can no longer drive and PLMD, apnea and bruxism and we do not know how this all ties together. Please help as I have a meeting in a few days I just found out about to discuss any options for being a contributor and earning smoe many as we are struggling. Regards

Answer:  I am sorry to hear about your energy problem. Red ragged fibers are found in normal muscle as we age. So, the presence of ragged red fibers does not indicate a mitochondrial disease, per se. The percentage of ragged red fibers is the key to suspect a diagnosis. If there is > 2% or so ragged red fibers after the age of 30 years then the suspicion increases for possible muscle disease. Did they find any other histochemical abnormalities on the muscle biopsies? Was there any biochemical testing on the muscle? Have you had any indication of muscle breakdown (elevated CPK levels)? Have you had biochemical labs that suggest that there might be a mitochondrial problem? Arachnoid cysts are usually benign, and are commonly seen. The usual treatment is just to watch and make sure they are not growing. For the most part, they do not cause problems. Does your PLMD keep you up at night? This might lead, in part, to your sleepiness. I would suggest a sleep study if you have not already had one. I am sorry that I cannot be of more help.

Answered by:  Russ Saneto, DO, PhD

Question:  With a diagnosis of Mitochondrial MELAS, is it safe to have a bone scan?

Answer:  A bone scan can be valuable to look for delayed bone mineralization. Bone density is measured by a dexa scan that uses a very small amount of radiation. The usual areas looked at are lumbar regions and hips for bone density. Then a wrist and elbow X-ray is used to measure the bone age. We then look for age-related differences between the chronological age and the studies. In adults most just use the dexa scan for bone density as there are standard numbers in the adult age ranges. If a problem is encountered then we can use medications to help increase bone density and hence limit long term effects of poor bone mineralization. This would offset the risks of the radiation, which is minor to begin with.

Answered by:  Russ Saneto, DO, PhD

Question:  My 12 year old son was diagnosed with mito this year. Since he was a baby, he has suffered from bouts of croup. We were told he would grow out of it. At age 9 he was sent to a pulmonologist who says he has reactive croup. No other explanation was given. Last week he had the worst case ever; we ended up in ER where he had a breathing treatment. We were told they had never administered a croup treatment to a 12 year old and they suggested seeing another pulmonologist. Additionally the lack of sleep from coughing so much along with the steroid and pain management med seem to be affecting him. This time his complaints of neck pain are extreme. Can this be related to mito? Any suggestions?

Answer:  I am sorry to hear about your son. Generically, croup is caused by viral infections, in particular parainfluenza (but can be any virus). However, croup can be from multiple reasons other than viral illness, such as reflux, allergies, etc. The usual age is from 3 months to 5 years of age, but as your son demonstrates, it can occur at any age. The “barking” cough is from swelling around the vocal cords. As you know, this cough gets worse at night (when the natural steroid decline in the system, just like in asthma). The cough usually presents a couple of days into the viral illness and then continues for the next 5 – 6 nights. Treatment depends on how severe the cough and frequency of the cough. Mild croup can usually be treated with humid cool air. My son did well with driving around the neighborhood at night, but it made his dad somewhat cranky. However, when the cough becomes intense and frequent, this can be worrisome-especially from a mitochondrial disease standpoint, due to energy output and muscle fatigue. In addition, dehydration and predisposition of becoming catabolic are possible and need to be watched very closely. In my practice, the standard treatments of steroids (usually injected into the muscle) but also oral inhaled steroids can sometimes be used (this is to reduce the swelling or edema around the vocal cords). If a child needs steroids, we usually will rehydrate with fluids containing carnitine and often watch overnight. Also, severe coughing can really fatigue muscles, especially the respiratory muscles used to cough. We are especially careful of our patients becoming so fatigued that oxygenation is compromised, so we follow this very closely. It is probably important to find a pulmonologist who will be attentive to your son’s mitochondrial disease and your son’s tendency for getting vocal cord region swelling during an illness. During the viral upper respiratory season, washing hands is extremely important. Getting vaccinated against the flu is also an extremely good idea.

Answered by:  Russ Saneto, DO, PhD

Question:  My children currently have a "probable" mito diagnosis based on some clinical symptoms of low muscle tone, muscle weakness & developmental delays, as well as some changes to the mitochondria in their biopsies including dilated mitochondria, abnormal cristae, and increased mitochondria in subsarcolemma. Recently my youngest son had the GeneDx 24 gene panel, and 2 variants were found, both on the SUCLG1 gene -G37A and V100L. It states on the test results that they are likely mutations, but our genetics doctor doesn’t believe that they are disease-causing in our children because the SUCLG1 gene mutations cause severe, often fatal, disease and my children are actually mildly affected. She said that these are "novel" mutations. Even though these may not be the specific mutations causing the disease in our children, does this finding mean that we are at least headed in the right direction as far as a more firm diagnosis?

Answer:  Most nuclear genes implicated in mitochondrial disease to this time occur in only one or a few families.  Thus, it is often the most severe presentations that are associated with the disease, with a broader spectrum of perhaps less severe disease findings slowly evident over time.  This seems to be the case with SUCLG1, which is a gene that encodes the succinate CoA ligase, and has been previously reported in only a handful of families.  Indeed, a recent study published by C. Rouzier et al in the Journal of Medical Genetics in 2010 showed that whereas severe disease occurs when SUCLG1 mutations result in no protein product being made, more mild disease occurs when residual SUCLG1 protein can still be identified.  In the latter case, there has also been reported other metabolic abnormalities including mitochondrial DNA depletion and mild methylmalonic aciduria.  Thus, it would be helpful to investigate residual frozen muscle on your son for mitochondrial DNA content (which is a clinically-available test that can be ordered) as well as whether his blood shows any methylmalonic acid.
 
Since it appears from your message that you have multiple, similarly affected children, it may be prudent to first determine whether this mutation properly segregates with disease.  What this means is that both of the SUCLG1 variants are found in all affected individuals, but no asymptomatic individuals harbor both.  In addition, since this is a recessive disease, it is important to confirm that each of these mutations was inherited from a different parent.  Finally, there are mutation pathogenicity prediction algorithms that can be used by the molecular laboratory that performed your study to predict how potentially damaging the specfic mutations identified might be, which could add further support for or against these mutations being thought likely to cause disease in your children.

Answered by:  Marni J. Falk, MD

Question:  I have heard about “cold laser” therapy that is supposed to speed up energy production in the mitochondria, and am wondering if that might help with mitochondrial disease, or make things worse.

Answer:  There are very few articles in pubmed [scientific search engine that lists all scientific publications resulting from research, including clinical trials and review articles] looking at Cold Lasers and mitochondrial function. It seems that they are currently only used for helping tissue regeneration; I am not sure of its utility in systemic mitochondrial disease.

Answered by:  Sumit Parikh, MD, Cleveland Clinic 

Question:  My 12 year old son was diagnosed with mito this year. Since he was a baby, he has suffered from bouts of croup. We were told he would grow out of it. At age 9 he was sent to a pulmonologist who says he has reactive croup. No other explanation was given. Last week he had the worst case ever; we ended up in ER where he had a breathing treatment. We were told they had never administered a croup treatment to a 12 year old and they suggested seeing another pulmonologist. Additionally the lack of sleep from coughing so much along with the steroid and pain management med seem to be affecting him. This time his complaints of neck pain are extreme. Can this be related to mito? Any suggestions?

Answer:  I am sorry to hear about your son. Generically, croup is caused by viral infections, in particular parainfluenza (but can be any virus). However, croup can be from multiple reasons other than viral illness, such as reflux, allergies, etc. The usual age is from 3 months to 5 years of age, but as your son demonstrates, it can occur at any age. The “barking” cough is from swelling around the vocal cords. As you know, this cough gets worse at night (when the natural steroid decline in the system, just like in asthma). The cough usually presents a couple of days into the viral illness and then continues for the next 5 – 6 nights. Treatment depends on how severe the cough and frequency of the cough. Mild croup can usually be treated with humid cool air. My son did well with driving around the neighborhood at night, but it made his dad somewhat cranky. However, when the cough becomes intense and frequent, this can be worrisome-especially from a mitochondrial disease standpoint, due to energy output and muscle fatigue. In addition, dehydration and predisposition of becoming catabolic are possible and need to be watched very closely. In my practice, the standard treatments of steroids (usually injected into the muscle) but also oral inhaled steroids can sometimes be used (this is to reduce the swelling or edema around the vocal cords). If a child needs steroids, we usually will rehydrate with fluids containing carnitine and often watch overnight. Also, severe coughing can really fatigue muscles, especially the respiratory muscles used to cough. We are especially careful of our patients becoming so fatigued that oxygenation is compromised, so we follow this very closely.

It is probably important to find a pulmonologist who will be attentive to your son’s mitochondrial disease and your son’s tendency for getting vocal cord region swelling during an illness. During the viral upper respiratory season, washing hands is extremely important. Getting vaccinated against the flu is also an extremely good idea.

Answered by:  Russ Saneto, DO, PhD 

Question:  I was diagnosed with mitochondrial myopathy in 2003, at the age of 50, although I have had symptoms for years. I recently developed a new problem of oxygen desaturation at night and with exertion, requiring supplemental oxygen. My pulmonary function tests are normal, and I have no cardiac issues. Could this be a complication of mitochondrial myopathy? If so, what is the prognosis and treatment?

Answer:  We see quite a bit of sleep desaturations in our patient population. Most of these patients have normal cardiac and pulmonary function. Sleep studies are consistent with a picture of central hypoventilation, in other words, the brain doesn’t remind the body to breath. Several of our patients have been placed on oxygen, either at night or throughout day. The patients using oxygen tell us they have improved energy and sleep better. Some patients have had decreases in their lactic acid values and all have described an improvement in their quality of life. None have had worsening of their symptoms since starting the oxygen. I would recommend evaluation by a local pulmonologist and possible use of supplemental oxygen during sleep (depending on the recommendations of your pulmonologist).

Answered by:  Mary Kay Koenig, MD 

Question:  I've been seriously struggling with my health for 6 years now. I am almost 39. I have excessive fatigue, muscle pain, weakness and knots, my whole body aches all day every day. I freeze during the day and sweat at night (even when our room temp is 62 degrees). I have a low pulse and low blood pressure. In September I got slammed with migraines nearly every other day, usually located behind my left eye that are now better controlled with norvasic (my blood pressure has been low for years). I have been forgetting things and conversations to the point that I am a bit scared. I have also lost my appetite which is not at all typical for me. As far as testing goes, I have high levels of lactic acid at rest and worse with exercise. I just got results from genetic testing that says I have heteroplasmy, a rare variance in m5673t>c(TRNAsn). What is that? I cannot find any research associated with this specific mutation. I have all the symptomology of MELAS except stroke-like episodes. Can you have MELAS without stroke-like episodes? Or would this likely be something else. I am nowhere near a specialist. Can you help me with some information? I sure appreciate the mito doctors.

Answer:  I am sorry to hear about your health problems over the past 6 years. Your symptoms may represent an underlying mitochondrial disease, but other conditions, such as disorders that affect the endocrine system, also need to be considered. It is most important that you are seen by a physician who can evaluate you carefully. Although there is not a mitochondrial specialist nearby, if at all possible I recommend you being seen in person by a doctor who specializes in mitochondrial disease. MITOMAP reports the change found in your mtDNA as a variant, but other tRNA-asparagine mutations have been associated with clinical disease. What this means is that a genetic change has been found in your mitochondrial DNA, and this change may be significant, but at present there is not enough information available to classify this change as truly disease-causing. It would be helpful to know, for example, whether this same change is found in other family members. Symptoms associated with MELAS are broad, and not every patient has stroke-like episodes. In addition, different mtDNA mutations can cause symptoms consistent with MELAS. Please if possible do get seen by a specialist.

Answered by:  Greg Enns, MD 

Question:  Since most mitochondrial disorders are characterized by reduced amounts of specific enzymes in the mitochondrial respiratory chain, is there potential to use enzyme replacement therapy to treat mitochondrial disease in the future? Is there anyone currently looking into this or is there a reason this won't work in mitochondrial disease?

Answer:  Excellent question. We have ERT for some disorders such as Pompe disease (lysosomal storage disease affecting muscle) but in those disorders there is a known transport protein (mannose-6-P receptor) on the muscle membrane and the lysosome that allows it to get from the blood to the muscle and on to the lysosome. Mitochondrial proteins are MUCH more complex in that many of the subunits are nuclear DNA encoded (~ 38 for complex I) and some are mitochondrial DNA encoded (7 for complex I) and the ones made in the cytosol (nuclear DNA encoded) must be targeted and transported into the mitochondria (MTS) via an elaborate transport mechanism – once inside the mitochondria they are assembled into the final enzyme with assembly factors (also from the nuclear DNA) and embedded specifically into the inner mitochondrial membrane. ERT is very inefficient in lysosomal disorders and the biology is very much more simple than the simplified version of the mitochondrial assembly I gave above.

Answered by:  Mark Tarnopolsky, MD, PhD, FRCP(C) 

Question:  Is there any correlation between mitochondrial disorders and cystic kidney masses? My son, who is 3 1/2, and has a probable mito myopathy diagnosis, had to have a kidney removed at 20 months old due to what was said to be a "multicystic nephroma". Until then, I had never heard of this, and although it can be genetic, nobody in our family has ever had this before my son. He also has multiple developmental delays and hypotonia, and although his muscle biopsy did not show any deficiency in the respiratory chain, the electron microscopy showed disorganized cristae, many dilated mitochondria, regernating basophilic fibers, and type 2 fiber atrophy, among other things i cannot recall. Do you think this kidney mass has anything to do with the mito issues, or is it just another rare thing that he had to deal with?

Answer:  Multicystic nephroma has no connection to mitochondrial disease that we know of. It is typically a rare type ofmalformation that occurs as the kidneys are developing.

Answered by:  Sumit Parikh, MD 

Question:  I am almost 60 yrs old and recently had a muscle biopsy that showed evidence of mitochondrial myopathy. I have had a variety of gastrointestinal (constipation, GERD, gastroparesis) and urinary tract dysfunction (hesitancy and retention) since a small child. My question relates to fluctuations in pain levels. My neurologist believes that in addition to the myopathy I have a small fiber neuropathy. I have noticed an increase in pain after eating meals and also after emptying my bladder. Is this something that is a feature of mitochondrial disease?

Answer:  It seems from the question that you are saying you have pain after eating and trouble emptying your bladder - and that these are due to a small fiber neuropathy which may be due to a mitochondrial disorder.

Small fiber neuropathies can lead to burning/tingling pain in the hands/feet, problems with circulation in the hands/feet, and slowed gastric motility which can lead to nausea and a sense of getting full easily. People with gastric motility problems can have bloating and feel pain from that. Small fiber neuropathies can be due to multiple causes, including some very common diseases (diabetes) and should always be excluded prior to assuming that the symptoms are from a mitochondrial disorder.

Non-specific symptoms of pain after eating (without findings of gastric dysmotility) and trouble emptying the bladder are typically not common or isolated symptoms of a small fiber neuropathy OR a mitochondrial disorder - the two may not even be related to each other and may require further evaluation.

Answered by:  Sumit Parikh, MD, Cleveland Clinic, Cleveland, OH