Ask the Mito Doc – October 2024 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.
Connecting the Dots Between Common Mitochondrial Diseases and Ultra Rare Diseases
Clinicians:
Andrea Gropman, MD, St. Jude Children’s Research Hospital, Memphis, TN
Bharatendu Chandra, MD, University of Iowa, Iowa City, IA
Q: Is it possible for patients with Mito to experience secondary adrenal insufficiency? Or should something else be considered to be causing it beyond the mitochondrial disease?
A: Andrea Gropman, MD: Mito patients can have anything else. I guess my best example is my patient who had MERRF, and had colon cancer. She was told by a gastroenterologist that her symptoms were because of her mitochondrial disease, because patients with mitochondrial disease can have GI symptoms. And I said, Well that doesn’t really make sense, I think there’s something else going on. And so it was found that she actually had colon cancer. So I think there is a danger. And, Bharat, you can comment as well. Is that so? There’s 2 problems. One is the not recognition, and then the other is the overgeneralization, because essentially mitochondrial disorders can affect any organ system that if somebody presents with something that it’s automatically lumped into mitochondrial disease, which it may not be, it could be a second comorbidity. In my experience, when I take care of adults, they come to me over diagnosed or under diagnosed. Either way they have a myriad of symptoms that nobody can put together, or they’re being overgeneralized. Once they get that mito diagnosis, everything’s being lumped into that and nobody’s looking further. So I think that I can’t answer in individual patients other than ones that I’m taking care of. But in general I think that it really behooves the specialists to rule out other things. I take care of patients with other metabolic disorders, and just because you have a metabolic disorder doesn’t mean you can’t get Alzheimer’s disease, or can’t get some other condition as well, you can have comorbidities.
Adrenal Insufficiency can be seen in some mitochondrial disorders, but certainly there are other etiologies for that, and so they have to be looked into carefully to see if they are related, or if it could be a secondary disorder.
Q: Is an elevated respiratory lactate related to Mito and would there be a cause for concern? Is there a way to treat it?
A: Bharatendu Chandra, MD: I agree with Dr. Gropman, because a lot of times it’s very easy to put the diagnosis of mitochondrial disorders. And given that there’s no biomarkers or no confirmatory testing, some of these patients will be on mitochondrial cocktails, and no one will be thinking of an alternative possibility. I’ve seen that for X-linked adrenal leukodystrophy, which is a paroxysmal disorder. But sometimes it can closely mimic mitochondrial disorders. So I personally feel that while it’s important to consider mitochondria as a possibility, we should also keep our mind open and think of alternative possibilities and be flexible in the sense that, let’s say there’s enough evidence that shows that it is likely something else than mitochondria, or it is likely a dual diagnosis. Then we should be able to try to work with collaborators or experts in that field to weigh in and see how we could resolve that because the ultimate goal is to have an accurate molecular diagnosis, because that is the thing that is needed for therapeutics or gene therapy, or anything else.
Q: Can someone have LHON PLUS symptoms without the standard vision issues of LHON?
A: Andrea Gropman, MD: Yes, we’ve seen a number of females who don’t have the vision issues, but have other issues, and in fact, have been diagnosed as having MS. We’ve actually seen a couple of males who are older, who still had some preserved vision. So there is variability, I think, especially for the LHON PLUS, it’s not fully understood. But yeah, we do see some who don’t have the vision issues, but certainly are at risk for vision issues.
Q: Should all mitochondrial patients consider taking taurine? If not who should consider it?
A: Andrea Gropman, MD: We have started recommending it to our patients, but particularly if they have a defect that can be improved by taurine. However, for those with epilepsy or autism we have added it to the clinical cocktail.
Q: Dr. Gropman, thanks for the great presentation and congrats on your new role!! What do you recommend for Mito patients prior to surgery, especially with some of the common medications being unsafe and many providers being unfamiliar with Mito?
A: Andrea Gropman, MD: Thanks. I am still able to do telemedicine if you want to see me, but the opportunity at St. Jude was just phenomenal for moving the field forward. We have prepared emergency letters. In it, we discuss which fluids are to be avoided and which anesthetics. We recommend the patient see the mito doctor before an elective surgery. In the event that a surgery is emergency, we ask a family member to tell the surgical team that the patient has a mitochondrial disorder and to discuss any and all anesthesia, fluids, meds, and diet with the provider.
Q: Please discuss about CPEO/KSS and what symptoms I should watch out for.
A: Andrea Gropman, MD: I can answer generically because I don’t know your exact case. However, heart problems can occur due to a conduction block, swallowing problems especially with fatigue, problems moving the eyes, so this presents issues with driving. Also, diabetes and endocrine disorders. Ptosis or the droopy lids can be an early symptom that brings one to diagnosis.
A: UMDF EDU/ Kara Strittmatter: We have plans for focusing on CPEO for January’s Ask the Mito Doc and KSS/Pearson in February. We will post speakers and details soon on our calendar at http://www.umdf.org/events.
Q: I have met several people in the LHON community with mutations in complex 1 that do not have other mutations, but have tested positive for Malignant Hyperthermia or had an MH episode. Are people with mutations in complex 1 susceptible to malignant hyperthermia?
A: Andres Gropman, MD: This is not a common finding. Is it possible they have other mutations that were not found? Other muscle disorders can be a risk for MH, not commonly, but we are learning more about this patient group and their atypical findings.
Q: Do people with LHON mutation have no other neuromuscular mutations?
A: Andrea Gropman, MD: In general no, but I have a LHON patient who also has a second mito dysfunction.
Q: On one of Dr. Chandra’s slides he had Progressive Supranuclear Palsy. What would be a possible mito differential diagnoses? (Paternal grandfather was diagnosed with PSP)
A: Bharatendu Chandra, MD: That’s a great question. Recently, there have been reports of certain mitochondrial genes that are associated with Parkinsonism, and especially progressive supranuclear palsy is a variant of Parkinson’s disease. So genes like POLG should always be considered. If someone has a family history of Parkinson’s disease, and if it’s young onset, then other genes, should also be considered.