Ask the Mito Doc July 2023
Ask the Mito Doc Panel during UMDF Mitochondrial Medicine 2023
Eva Morava-Kozicz, MD, PhD, Mayo Clinic
Austin Larson, MD, Childrens Hospital of Colorado
Russell Saneto, DO, PhD, Seattle Children’s Hospital
Jaya Ganesh, MD , Icahn School of Medicine at Mt. Sinai
Abdulrazak Alali, MD, Akron Children’s Hospital
Muge Gucsavas Calikoglu, MD, MPH, University of North Carolina Health
Q: Suggestions for sick plan/emergency care?
A: “Abdulrazak Alali, MD”
What the manifestation in each organ system is eg – diabetes, arrhythmia, renal disease etc
What are the possible complications
What medication to avoid
Management of acute complication- example what should the Emergency docs do if you are having a stroke
Every person not need every single thing I listed but your doctor will be able to syntheses information.
Q: Will insurance cover a reasonably priced mito cocktail? Our daughter cannot swallow pills, what can we do?
A: “Muge Gucsavas Calikoglu, MD, MPH. There is suspension form of carnitine but not for others, most insurances do not cover supplements, it is possible to crush some vitamins and give to kids in apple sauce. “Austin Larson, MD” There is a website bulksupplements.com that offers many components of typical mito supplements as bulk powder and is typically reasonably priced
Q: Is myoadenylate deaminase deficiency classified as a mitochondrial disease?
A: “Austin Larson, MD” My understanding is that myoadenylate deaminase deficiency is equally prevalent in the population in those with and without symptoms, so that condition may be a biochemical variant that does not have clinical significance. Generally, if I see a symptomatic patient that has myoadenylate deaminase deficiency then I will look for other diagnoses
Q: Is there any correlation between mitochondrial disorders and autism or other neurodevelopmental disorders
A: “Abdulrazak Alali, MD” Many patients with Mito disease present with nonspecific symptoms that often mimic neuro developmental disorders or even autistic features.
A:”Muge Gucsavas Calikoglu, MD, MPH” Some patients with mitochondrial disorders indeed may present with autism. In children with autism you will need genetic testing to determine etiology and depending on clinical symptoms, mito sequencing may yield answers
Q: Is there any correlation or connection between mito disorders and cancer? specifically thyroid cancer
A: “Austin Larson, MD” there are certainly some mitochondrial enzyme deficiencies that have a clear association with cancer like SDHA, SDHB, SDHC, SDHD, FH def – paragangliomas, phenochromocytomas; I’m not aware of a thyroid cancer link
Q:Best way to prevent infections as a mito patient?
A: “Abdulrazak Alali, MD” Universal precautions such as hand washing and Immunization continue to be the key.
For specific disorders like Pearson who can have immune defy appropriate therapy like GCSF may be used. Age appropriate vaccines, including adult vaccines to prevent pneumococcus and frequent hand washing especially in public areas, good nutrition especially many patients with mito may have vitamins and nutrition deficiencies.
Q: Are there any contraindications for the use of Spravado?
A: “Austin Larson, MD” I’m not aware of any contraindications for esketamine for patients with mitochondrial disease.
Q: My doctor wants me to begin a mito cocktail to help with fatigue and exertion intolerance. It includes riboflavin, l carnitine, coq10, vit E, etc….I was just wondering if there’s a particular brand that you recommend (quality and purity)?
A: “Muge Gucsavas Calikoglu, MD, MPH” I don’t recommend specific brands, cost is an issue for many families, a reputable brad from CVS, Walmart works well.
Q: How many people diagnosed with me/cfs (chronic fatigue syndrome) have a mitochondrial disease?
A: “Muge Gucsavas Calikoglu, MD, MPH” i don’t think there has been a comprehensive epidemiological study to determine this. if your beyond fatigue such as ptosis, cardiac issues, the yield of a mito disease will be higher.
Q: Tips for patients with a muscle biopsy that indicate mitochondrial disease, but no causative gene identified yet?
A: “Muge Gucsavas Calikoglu, MD, MPH” Review of the muscle biopsy, what is a fresh sample? Second opinion at a larger center such as CHOP or Columbia or Seattle.
“Austin Larson, MD” I think that if an expert physician has a suspicion of a genetic basis for your symptoms, then whole exome or whole genome sequencing would be a good diagnostic test in that scenario.
Q: Are some people with mito hypoglycemic after eating after 5 hours? Could becoming sick due to a delayed meal be mitochondrial disease? Symptoms include; severe headaches, nausea, tension, disorientation and general discomfort. symptoms alleviated after eating
A: “Muge Gucsavas Calikoglu, MD, MPH” You may have an issue with insulin, other endocrine issues, these would need to be evaluated.
“Abdulrazak Alali, MD” I tell my patients to avoid prolonged fasting especially when they are sick – have seen my pediatric patients do worse when they are sick and don’t want to eat. I may suggest an ER visit for IV fluid’s especially for the sick kids.
Q: I don’t have a diagnosis and I’ve seen many providers. i can only see specialists by referral from primary care but running out of resources and afraid to travel and not wanting to waste money for no answers. is there a mito specialist I can just ask questions to?
A: “Abdulrazak Alali, MD” https://www.mitonetwork.org/ This provides all centers approved. See what is near you and ask for a referral.
Q: What percentage of people with adult onset mito disease benefit from the mito cocktail? And how long does it take before it starts working?
A: “Austin Larson, MD” We don’t know the answer to this question and it’s a difficult study to design and execute. I think that general rules are to not cause yourself financial hardship and to try things one at a time to try to isolate the effect of an individual intervention. I think that each patient will need to decide for themselves if this is an intervention that is financially feasible for them to try. If you can try supplements for a few months without causing financial hardship, then I think that would be a reasonable timeframe.
Q: How do we find the source of pain in a nonverbal child? She is screaming and we cannot find her source of pain, even after testing and seeing providers. any suggestions she is 12?
A: “Muge Gucsavas Calikoglu, MD, MPH” Is it reflux, constipation? They are often the most frequent reasons, sometimes we can give medication for dulling the pain such as gabapentin, please see your neurologist.
Q: Suggestion on how to answer questions from mito children, as they become aware of disease? Questions like, mom can I have children someday or will I pass on my disease? or How did I get Leighs disease?
A: “Muge Gucsavas Calikoglu, MD, MPH” Be honest and explain based on age and maturity
genetic counselors are excellent at guiding you through these questions. There are excellent internet resources and we will review and make sure this is also addressed on the UMDF site.
Q: Iron supplements/infusions seem to be tricky with mito–tips to manage deficiency safely?
A: “Austin Larson, MD” we have good biomarkers to assess for iron deficiency (ferritin/iron saturation/ TIBC). Providers in several specialties should have experience in finding the right dose to address deficiencies and treat to effect. I have found that some patients tolerate iron-polysaccharide better than iron sulfate.
Q: My neurologist said he’ll refer me to a mito specialist only if I benefit from the mito cocktail. Is this standard? I was just really hoping to see a mito specialist sooner as I’ve had these symptoms for many years
A: “Austin Larson, MD” My recommendation would be for the neurologist to use broad genetic testing to try to identify a specific diagnosis, which can be more accessible than seeing a mitochondrial clinic.
Q: From AG: have had high blood pressure for years, now labeled microvascular disease, is there a connection to mito?
A: “Muge Gucsavas Calikoglu, MD, MPH” No
Q: is there a false negative result for mito?
A: “Austin Larson, MD” Any test has some risk of false positives and false negatives, so it is important to have an expert clinician interpret the significance of a test result in the specific clinical context that you’re in
Q: What is mitochondrial IV and the difference between the others?
A: “Muge Gucsavas Calikoglu, MD, MPH” Complex IV defect is usually a result from a muscle biopsy, today the gene testing is needed for further definition before any comparison can be made.
Q: is mito associated with hypoxia? can hypoxia be from cardiovascular issue?
A: “Abdulrazak Alali, MD” Sleep apnea is very common in mitochondrial disorders and cause hypoxia. Sleep studies are recommended. yes of course, we recommend comprehensive cardiac evaluation
Q: can a geneticist test me for both mito and metabolic myopathy?
A: “Austin Larson, MD” Yes, there are genetic tests that assess for both mitochondrial diseases and other metabolic myopathies in a single test.
Q: Patient care standards mentioned stroke like visible abnormalities that might show up in MRI, can you expand on that?
A: “Austin Larson, MD” For patients with a specific diagnosis that is associated with stroke like episodes then MRI is indicated in the setting of new focal neurological symptoms.
Q: Does adult onset mito disease change its symptom profile over time? For instance, I developed temporary bouts of dizziness and profound fatigue in 2010-2012. Then from 2012-2016, I developed weakness/pain in both thighs and both upper arms, like a profound fatigue type of weakness, and it affected my ability to walk upstairs and stand from a seated position. I also had a body wide inflamed feeling and lightheadedness. I was randomly diagnosed with celiac disease in 2016 and removing gluten “substantially” helped my symptoms. Then I started vyvanse and felt great for a year. Then I woke up one day in 2017 with profound fatigue, orthostatic and exertion intolerance and heaviness in my head/eyes, and when I push myself, I feel like I have the flu (sore throat, malaise), and pushing myself also causes high bp and hr (though resting bp and hr are normal). Does this sound like mito? I just really want to get better.…
A: “Muge Gucsavas Calikoglu, MD, MPH it sounds like you have postural orthostatic syndrome also patients with celiac disease may have folate deficiency and vitamin B12 deficiency. please have these checked before thinking about mito.
Q: Is vertigo for 6 weeks common, anything other than anti-seizure meds that are useful?
A: “Austin Larson, MD” I would say that this is typically a symptom that is evaluated by an ENT physician, so that would be a place to get evaluated for that
Q: Does mito cause orthostatic hypertension?
A: “Austin Larson, MD” some patients with mitochondrial disease do have orthostatic hypotension, but there are many other reasons for that symptom other than mitochondrial disease as well.
Q: For those with a rare VUS, are there functional testing avenues to see if it is causative?
A: “Austin Larson, MD” Sometimes there are functional assays available. It depends on the gene, so that would be a good topic for a consultation with a geneticist
Q: Are there any new noninvasive, non-genetic tests for mito, such as assays, that have become available?
A: “Austin Larson, MD” There are some newer biomarkers that can help to identify scenarios with higher suspicion for mito disease. For example, GDF15 is elevated in association with some specific mitochondrial diseases, but identifying a specific diagnosis almost always requires genetic testing.
Q: Specific gene testing companies you trust? Diagnosis came from Ivitea and Genedx. neuro ophthalmologist did testing due to vision loss.
A: “Muge Gucsavas Calikoglu, MD, MPH” Both are very good
Q: Other than mito cocktail, any other supplements helping with exercise intolerance?
A: “Muge Gucsavas Calikoglu, MD, MPH” Some try creatine but hydration and good nutrition is paramount.
Q: Do you have recommendations for patients being their best advocate for themselves and working with the care team
A: “Austin Larson, MD” I would recommend finding providers that you have a good personal rapport with and someone that is willing to spend the time to understand your goals and values and provide you an expert opinion about how to achieve your goals
Q: What do each of you do to keep spirits up while taking care of your patients? any ideas out here for us parents who are struggling?
A: “Muge Gucsavas Calikoglu, MD, MPH” The smile on a child’s face keeps me going.
“Abdulrazak Alali, MD” It is not easy I do have the need to have a good cry especially when I am taking care of children. But the patients and the fortitude they show keep me inspired and going.
Q: Can the gene editing process be used across all mito genes?
A: “Austin Larson, MD” Certain gene editing platforms will be amenable to certain genes, certain platforms can only correct the gene in certain tissues. We learn from each trial (positive or negative) and can apply those learnings to each subsequent disease for which therapy is developed
Q: What’s the best diet or supplement to support low amino acids, specifically I have low Taurine, Serine, Threonine, Alanine, Proline, Ornithine, Lysine, and Tyrosine
A: “Muge Gucsavas Calikoglu, MD, MPH” Increase your protein intake discuss with nurititionists.