Ask the Mito Doc – February 2025 Q&A
All answers today are based on personal experience of the participants. As always, please consult your personal physician prior to taking any action.
Ask the Mito Doc – February 2025: Comprehensive Care in Kearns-Sayre and Pearson Syndromes: Diagnosis, Symptom Management and Support Strategies
Clinicians:
· Rebecca Ganetzky, MD, Children’s Hospital of Philadelphia
· Sumit Parikh, MD, The Cleveland Clinic
Q: Is there a difference between KSS & CPEO? I.E.: genetic testing & results; symptoms; severity & progression of disease, etc.
A: Sumit Parikh MD: The DNA change can look the same but some people only have the eye symptoms (CPEO) while others have a more severe form (KSS) and we do not completely understand why this is.
Q: Did you say that life expectancy in KSS is often related to or correlated with age of onset, or that is not generally so, where children diagnosed at an earlier ages can typically be expected to live as long as children or young adults diagnosed at older ages?
A: Rebecca Ganetzky, MD: Actually I didn’t mention that, but we have found that life expectancy does correlate with age of onset – so the younger a patient is diagnosed, the worse the prognosis in general.
Q: What types of specialists should a patient with either KSS or Pearson syndrome make sure that they’re visiting yearly? Are there any special doctor visits that they might want to consider?
A: Rebecca Ganetzky MD: That’s a long list. And it changes over the course of the life of a patient with Pearson or Kearns Sayre. Everyone should be seeing a cardiologist at least once a year, but probably even more frequently at certain ages. Everyone should be seeing an ophthalmologist once a year. Everyone should be getting their hearing tested once a year. From there, there are a lot of guidelines but I don’t want to over medically burden my patients so I have to be selective about who I say they have to see every year. Exactly as Dr. Parikh said, especially the kids who have a history of Pearson syndrome. Renal involvement, kidney involvement can be a really serious cause of morbidity and mortality. I’d love to hear what you (Sumit Parikh MD) do, but in my personal practice I don’t involve renal right away. I do the renal screening myself and then once that becomes abnormal I send them to renal. I don’t know if you do anything different. I think that also strongly points out the most important person, which is someone who’s the team coordinator, and that can be different for different patients. That can be a complex care pediatrician, that can be a geneticist, that can be a neurologist; But someone who’s willing to say, yes, I will call the ophthalmologist, yes, I will check your blood sugars and your hormone levels and tell you when it’s time to see an endocrinologist, yes, I’ll follow your kidney levels. Many of my patients stop needing to see hematology when they stop getting transfused, but they may still have a little abnormalities here or there and need to know when that’s severe enough to re-call the hematologist and get them involved. So that person, whoever that person is, is really important.
A: Sumit Parikh MD: All of our teams are fortunate enough to have multiple specialists from the pediatric and adult side. But it really wouldn’t be great to have each patient see all 20 people so we really do try to personalize it and prioritize who they need to see right away based on the symptoms they have, and then slowly introduce other team members when needed. I think that’s much more reasonable.
Q: Is beta thalassemia minor & KSS called sideroblastic anemia?
A: Sumit Parikh MD: These are different issues and not linked to mitochondrial disease on their own. Sideroblastic anemia has other causes, though it can be seen with some mitochondrial diseases like Pearson syndrome. B-thalassemia is just its own separate thing.
Q: Are there any special dietary concerns for patients that have KSS or Pearson syndrome?
A: Rebecca Ganetzky, MD: I believe that there is a correct diet approach for mitochondrial disease. And I also believe that I do not know what it is. What I know is true, is that there may be diet concerns for diabetes and there may be diet concerns for renal disease. Each of the organ systems may have their specific considerations. Our bodies are designed to eat food to provide us energy. Mitochondria get in the way of that but it still probably makes sense to eat the foods that are the most naturally coexisting with humans that are part of human historical diet because they support our mitochondria to make as much energy as possible. So I usually encourage my patients to pursue foods that have lots of naturally occurring nutrients in them, lots of naturally occurring antioxidants that are colorful and that utilize different parts of our energy pathways – some carbs, some proteins, some fat so that we’re not traffic jamming those roads into the mitochondria. I don’t know that that’s the right answer, it just makes logical sense to me.
Q: Are there any specific supplements that people with single large scale deletion should be taking?
A: Sumit Parikh MD: Many of you have heard this before, that the supplement story is a little bit all over the place and everybody has their own favorites, but I suspect almost everyone agrees that folinic acid, a type of folate that crosses over to the brain is essential, especially for people with Pearson’s and Kearns-Sayre. In the past, we used to do spinal taps routinely and we would find low levels. This has been documented by many researchers. And we know that without healthy amounts of folic acid in the brain, the brain can’t grow, the brain can’t turn over well and do its job. So now we don’t do spinal taps routinely, but based on age and size, almost all of us, I suspect, are using a prescription for amino folic acid called folinic acid. Outside of that, I suspect there’s a lot more variability in what people are receiving.
A: Rebecca Ganetzky MD: I agree completely, but with the critical caveat that that’s not an evidence-based approach, that’s just what we do. I think folinic acid is incredibly important. I’d like to comment that seizures are very, very, very rare in Kearns-Sayre. If a patient is seizing, usually they’re hypoglycemic. Or they’re hypocalcemic. But sometimes it can also be that they have seizures from cerebral folate deficiency itself, and that can get better with folinic acid. So that, to me, is the most critical. Our ophthalmologists are now increasingly recommending N-acetylcysteine and lutein for retinal protection. I think that is the next most universal supplement in Kearns-Sayre; they’re very benign supplements and they may protect the retina.
Q: How much folinic acid is recommended?
A: Sumit Parikh MD: There’s not a fixed dose in the sense of it is weight-based and size-based. Your mitochondrial team should know how much they should be using. But in general, for babies, that’s 5 to 10 milligrams twice a day and then it starts moving up from there.
Q: What about CoQ10?
A: Rebecca Ganetzky MD: Q10 is commonly used, but guidelines are not specific to KSS.
Q: Are there any special anesthesia precautions for people with KSS or Pearson syndrome.
A: Sumit Parikh MD: We have historically always talked about anesthesia precautions but what we’re realizing is that a lot of these needs were based on how anesthesia used to be practiced 15 or 20 years ago, and the more recent work that’s been done, a lot of it in Europe, people are not having problems with anesthesia. In general, the modern approaches to anesthesia are well tolerated and do not bring out mitochondrial symptoms for most, especially if they’re going into a planned surgery and they are at their baseline state of health. That being said, there are a few things where we are probably spoiled because our anesthesiologists that we work with are very familiar with mitochondrial disease and they might be just being extra cautious and we don’t realize it. There are some guidelines that we have out there that we would want a less familiar anesthesiologist to follow. But it really just means making sure that they don’t automatically give the full dose of anesthesia unless the patient needs it and monitoring their vitals and their blood work a little more closely. That’s one big one. And then the second big one is there has always been some concern about giving a medicine called propofol, but we’re finding that propofol is generally well tolerated. In the old days, like 20 years ago, we used to use propofol for days and days and that just doesn’t happen anymore. We have better choices. So most of the time, propofol is now only used for a couple of hours. The vast majority of mitochondrial patients have no trouble with that. So a lot of those old precautions, when we rewrite our guidelines, we’re going to be probably removing a lot of those precautions. One thing that some families don’t know about is that you can actually meet with your anesthesiologist weeks to months before your surgery. That’s kind of a standard of care for us when something planned is happening. Having that anesthesiologist meet with you and get to know your family member’s history is nowadays very standard of care for complex patients. They take a lot of those things into account and then they will make a detailed plan with the whole team.
A: Rebecca Ganetzky, MD: I completely agree with you in general. And would say, yes, almost all patients tolerate anesthesia well. I say exactly what you say. Start low. Go up slow, but most pediatric anesthesiologists do that anyway. For Kearns-Sayre in specific, these aren’t anesthesia precautions in particular, but they’re perioperative precautions that are really important. The first is that many, if not most patients especially with Kearns-Sayre, have hypoparathyroidism. Their body doesn’t regulate the calcium level in the body, and when they’re stressed that can go from normal to so low that it’s causing problems with muscle movement very quickly. I often will give my patients either stress doses of calcium or parathyroid hormone, or just say, check the calcium. It’s really easy to fix if it’s low. But I give really careful precautions about that. If patients have kidney disease, they may need kidney dosing of the medications around anesthesia, post-operative antibiotics, and other medications like that. So that’s an important thing to keep in mind. And patients with Kearns-Sayre in particular often have diabetes. And what I found in my experience is that they’re not diabetic like other kids are diabetic; They have a non-type 1, non-type 2 diabetes that isn’t just an insulin deficiency. There’s also usually some component of insulin resistance but they also are very brittle, meaning their sugar can get really high, but it can also get very low very quickly. So making sure that you have a good diabetes plan, you know how the sugar responds to those hypoglycemic agents and you’re monitoring the sugar really, really carefully with a good backup sliding scale of insulin as needed to keep the sugar under control so it doesn’t get too high from stress and it doesn’t get hypoglycemic from over control.
Q: You talked a good bit about mental health issues in these two syndrome groups, what kinds of interventions have you found to be successful and what can families look for so that they can get a head start on mental health care for their children?
A: Rebecca Ganetzky MD: A lot of different interventions exist for mental health. I think a lot of the mental health concerns, in my opinion, are reasonable concerns about the anxiety and life disruption of having a disease with an uncertain, unpredictable, progressive course. That’s really scary. So I think naming that and making sure that there is a mental health professional(s) to support that truth for the family and for the patient. Another piece of that is providing services to make sure that patients can have as much autonomy as possible. Another thing that I’ll say is that there is some evidence that cerebral folate deficiency can have some symptoms of mood and anxiety. Often when my patients acutely have worsening of their mental health symptoms I’ll make sure that they’re getting as much folinic acid as they should be in addition to bringing in other mental health supports, making sure that we’re not missing other medical symptoms that can cause mental health symptoms and really treating the patient holistically is critical. To me one of the most fundamental things is trying to keep our patients doing as much as possible, as involved in their community as possible, having as much social support as possible.
A: Sumit Parikh MD: The only other thing I might add is that there is a need for medication for anxiety for these kids and adults. This has not just something to do with the fact that they’re going through a chronic illness, but these individuals’ brains are affected by disease and are clearly working differently. So this is definitely not a mind over a matter situation. And we often use a glasses analogy: If your eyes are shaped differently, you need glasses. You can’t strain past that problem. If your brain is wired differently or working differently, you can’t just strain past that problem. As long as they don’t cause side effects, we should not tolerate side effects.
Q: What about the medication piece of going to a psychiatrist? Are there Mito savvy psychiatrists out there? Or is it best for that patient’s team leader to do the introduction to the psychiatrist or whoever would be prescribing that kind of medicine?
A: Rebecca Ganetzky, MD: It’s highly, highly variable. There are one or two psychiatrists that I found who are metabolic and genetic disease gems. We’re lucky enough to have a neuropsychologist on our team. She doesn’t provide psychiatric medication, but she can help tell us what the diagnosis is. As a geneticist, sometimes I’m struggling to say, is this an anxiety disorder? Is this a mood disorder? Some of my patients, as they start to lose vision, may have some visual hallucinosis and trying to figure out where that fits. So she can help translate the psych part to me and I can help translate the genetic part so that she knows and the two of us together can help onboard a psychiatrist into the situation. It’s really helpful to have a good back and forth between the psychiatrist, even if they know Mito in general, there’s so much different organ system involvement, it is helping you say, these are the side effects to look out for, can we work together to find the right med for the patient? It can be really, really helpful.
A: Sumit Parikh, MD: The only other thing I would add is that it will be wonderful to have somebody in every specialty who is really interested in mitochondrial diseases, but depending on which part of the country you’re in or if somebody is moving for a job, that just may not always be available. As long as you have a team leader and a specialist who’s interested and willing to learn and willing to read, that goes miles and sometimes it’s better than somebody who thinks they know everything about this and don’t need talk to anyone. The other part is that as a whole, our management of many of these symptoms, whether they be psychiatric or other, are not specific to the underlying disease. We don’t understand many diseases well enough to know whether we need one medicine over the other. We have some (patients) that we avoid medication, but otherwise how a psychiatrist manages anxiety or depression for that age group is awfully similar for mitochondrial disease and non-mitochondrial disease.
Q: My twin girls, 12 years old, have KSS. When they have a Mito crash, they go into a ‘state’ where they sleep for 11 days and really struggle to wake. They don’t want to eat or drink anything and often vomit if they do. Their personality changes during this time where they talk differently, facial expressions are different and they are very scared. We have been told by a psychiatrist that this is due to them having severe anxiety and use this as a defense mechanism but then we were also told by our metabolic specialist that this is due to KSS and it’s their body crashing and they need to regain their energy. Is there others that this has happened to and is there anyway we can short live the experience? Thank you.
A: Rebecca Ganetzky, MD: Thank you so much for asking. Yes, we have seen similar things in other patients with KSS and it can be incredibly challenging to parse out what is happening clinically. It is very important to rule out any medical problems, like hypocalcemia, cardiac rhythm changes, blood sugar highs or lows or adrenal insufficiency.
Q: What are the Mito doctors’ opinion on taking Methylene Blue if you have Leigh’s disease?
A: Sumit Parikh, MD: There is no medical evidence to support this at this time.
Q: My 12 year old daughter is very active. She sometimes complains of leg pain, should I slow her down? Is there anything I can do to help her?
A: Sumit Parikh MD: In general if she is able to recover after a short break or by resting overnight – there is no need to slow her. Sometimes electrolyte fluids (Propel for example) can help.
Q: Is a left anterior fascicular block a conduction block?
A: Sumit Parikh MD: It is the start of a conduction block like condition.
Q: What kidney doctors are on the Mito team at CCF?
A: Sumit Parikh MD: We have pediatric and adult nephrology experts and have a transplant team when needed.
Q: Dr Parikh, what about the littles with Pearson? How do you get them growing and get them beefed up a little bit when they’re young?
A: Sumit Parikh, MD: Oh, that’s all gastroenterology and endocrinology helping us out. That’s definitely not me. I think one of the things we did learn, and some of this was actually through the CHAMP Foundation’s database is that starting pancreatic enzymes if somebody’s not growing can be helpful even if their lab work’s not showing a clear problem. So there are these little insights that we can provide our GI doctors or endocrinologists, but really they’re doing all the heavy lifting.
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