Understanding Mitochondrial Disorders - Sumit Parikh MD
January 14, 2010 | Reviewed on January 28, 2014 by Sumit Parikh, MD
Cleveland_Clinic_Host: Mitochondrial disorders can affect organs, motor function and the nervous system. Individuals experience a wide array of symptoms and degrees of severity. Although commonly seen in infants and children this chronic and genetic disease can develop at any age. Diagnosis of this disease can be difficult. Cleveland Clinic Pediatric Neurology is ranked in the top 4 in the country with many of its physicians specializing in the research and treatment of mitochondrial disease.
Mitochondria are tiny organelles found in almost every cell in the body. These organelles are responsible for creating 90% of cellular energy necessary to maintain life and support growth. Mitochondrial disease is when mitochondria in the cells fail to produce enough energy to sustain cell life. When enough cells cease to function properly organs, motor functions, and the neurological system can become impaired. This chronic and genetic disease affects one in every 4,000 children by the age of 10 in the United States. Mitochondrial disease is often misdiagnosed due to the fact many of the symptoms are synonymous with other, more common, diseases. To learn more about the causes and symptoms of this disease join the Cleveland Clinic in a free web chat with our neurologist and mitochondrial disease specialist, Dr. Sumit Parikh.
Cleveland Clinic Pediatric Neurology ranked in the top four in the country with U.S. News and World Report and ranked No. 1 in Ohio. Each year our world renowned neurologists and neurosurgeons oversee more than 10,000 patient visits. The Pediatric Neurometabolic and Genetic Disorders Program provide diagnosis and treatment for the complex genetic and metabolic disorders that underlie many pediatric neurological and developmental issues, such as mitochondrial disease.
Sumit Parikh, MD, is a neurometabolic and neurogenetics Staff Clinician at Cleveland Clinic. He specializes in the evaluation, diagnosis and treatment of developmental delay, neurodegeneration and metabolic disease. Dr. Parikh is the Co-Director of the Cleveland Clinic Mitochondrial Clinic and the Cyclic Vomiting Syndrome Clinic.
In 2007, Dr. Parikh was selected as one of "America's Best Doctors." He serves as a medical advisor to the United Mitochondrial Disease Foundation and Cyclic Vomiting Syndrome Association. He is a councilor of the Mitochondrial Medicine Society and serves on their Diagnosis Standards and Outreach Committee. He also serves as the Society's website administrator. He is on the scientific planning committee of the Child Neurology Society, and serves on both the Cleveland Clinic Child Advocacy Board and Autism Standards Committee. He is a reviewer for the Journal of Child Neurology.
His clinical interests include the diagnosis and treatment of patients with mitochondrial cytopathies, inborn errors of metabolism, cognitive and developmental regression and developmental delays.
To make an appointment with Dr. Parikh or any of the other specialists in our Pediatric Neurology and Neurosurgery Services at Cleveland Clinic, call toll free at 866.588.2264. You can also visit us online at www.clevelandclinic.org/pediatricneurology
Cleveland_Clinic_Host: Welcome to our Online Health Chat with Dr. Sumit Parikh. We are thrilled to have them here today for this chat. Let’s begin with the questions.
Overview Mitochondrial Disorders
keeptrying: When a mitochondrial disease presents in an adult, does that mean that that person had the problem their whole life, or that it just developed?
Speaker_-_Dr__Sumit_Parikh: It depends. We differentiate between primary (genetic/born-with) mitochondrial disease and secondary mitochondrial dysfunction.
Some individuals have an inherent mitochondrial vulnerability or problem with how their mitochondria work - and the symptoms accumulate over time. Since we have a thousand mitochondria in each cell and a trillion cells - we literally have a gazillion mitochondria. In mitochondrial disease, a person may have a certain percentage of a gazillion not working -> if it is a small percentage -> their symptoms may not begin until later in life or be 'milder.'
Mitochondria are also very vulnerable to damage from other diseases (diabetes), medications (chemotherapy) and toxins (smoking). In these situations, a person may have mitochondrial issues show up after chronic exposure to these offending conditions/agents.
keeptrying: What differences are there, if any, between the way a mitochondrial disorder presents itself in a child versus an adult?
Speaker_-_Dr__Sumit_Parikh: As stated in the prior entry - mitochondrial disorders present differently depending on how severely they are affected. Also - each organ in our body has different pools of mitochondria - and each pool of mitochondria can have varied levels of health as well.
Thus - if a person has many mitochondria affected (of their gazillions) or they are all not working up to speed - symptoms begin early. If the mitochondrial dysfunction is 'milder' or fewer individual mitochondria are affected, symptoms begin later in life.
jheister: Does mitochondrial disease worsen / progress with time, or can it improve?
Speaker_-_Dr__Sumit_Parikh: As one of the previous replies may have alluded to - since there are many types of mitochondrial diseases of varying severity - the answer to your question is that it can do any of these things.
Some patients have chronic symptoms that only worsen during times of medical/physiologic stress. Others can have a slow steady or rapid downhill progression.
keltonCoop: Is there a direct link between life expectancy and the type of mutation present?
Speaker_-_Dr__Sumit_Parikh: As some of you may be picking up - there is no yes/no answer for mitochondrial disease. For life expectancy and mutations, the answer is that it depends on the type of mutation and how many of the 'gazillions' of mitochondria are affected (which we can sometimes quantify when the mutation is known).
platinum: How often do you see mitochondrial disease affecting the immune system?
Speaker_-_Dr__Sumit_Parikh: This topic is still actively being studied. We know that mitochondrial dysfunction leads to more chronic non-life-threatening infections (colds, ear-infections) - and in some patients - having these medical stressors recur frequently leads to a decrease in quality of life.
We do not have a treatment yet though we are more judicious about illness prevention and having an immunologist and infectious disease expert help us with our patients.
Immunoglobulin therapy (a blood product with each dose requiring several thousand donors) is being studied but has not been proven as effective therapy.
hannah: What causes demyelination? Would a high protein diet/ketosis help children with this problem?
Speaker_-_Dr__Sumit_Parikh: Demyelination is a 'generic' word to describe damage to the myelin (coating) around the nerves (whether in the brain or body).
There is no specific diet that helps individuals with demyelination.
johnp: Are Type 1 Fiber Predominance and irregular size muscles fibers the same thing?
hyatt02: My 4 year old daughter has severe diarrhea from the medications she is taking. What can I give her to help with this?
Speaker_-_Dr__Sumit_Parikh: I would defer this question to a gastroenterologist. If the diarrhea is due to supplements (carnitine), lowering the dose and giving it over more intervals (3-4 times a day) and ensuring that you give it with food may help.
If the diarrhea is from dysmotility - a GI doctor can prescribe medication that may help.
Types of Mitochondrial Disorders
gramps: My grandson was recently diagnosed with Complex III Mito Disorder. What is the difference between Type I, II III, IV, V or whatever? Does the higher number mean it is worse? Can a person have more than one?
Speaker_-_Dr__Sumit_Parikh: The various numbers refer to the various portions (departments) in the mitochondria. A higher number is not worse - it just helps physicians know which part of the mitochondria might not be working well and direct genetic testing.
It turns out that these mitochondrial components live meshed together and by having one portion not work properly - another portion may also not work as intended - so yes - a person can have more than one Complex affected.
jackson: I have NARP (Neuropathy, ataxia and retinitis pigmentosa (NARP) syndrome) and associated muscle pain in my legs. I also have joint pain in one knee. Is this related?
Speaker_-_Dr__Sumit_Parikh: Mitochondrial disorders typically do not cause joint injury - though muscle disorders lead to more stress on joints and can exacerbate or bring out a 'minor' joint problem that comes about with 'normal' aging.
junior: I am 48 and was diagnoses with MERRF syndrome (Myoclonus Epilepsy Associated with Ragged-Red Fibers) about 10 years ago, that has been getting progressively worse. I get fatty tumors that have to be removed surgically. Are these tumors related to the MERRF and is there any way to try and prevent their growth?
Speaker_-_Dr__Sumit_Parikh: Fatty tumors (lipomas) can be seen more commonly in certain mitochondrial disorders. There is no way to prevent these.
LHoward: Can you give me any insight into CPEO, such as progression and treatment? Thanks.
Speaker_-_Dr__Sumit_Parikh: CPEO - chronic progressive external ophthalmoplegia - can vary in severity and progression (as can all mitochondrial disorders). The treatment for most mitochondrial disorders is similar -maintaining good health and nutrition, avoiding mitochondrial toxins and considering anti-oxidant supplementation.
dorcie: Is Diffuse Louis Body Disease a form of mitochondrial disease or dysfunction?
Speaker_-_Dr__Sumit_Parikh: Likely leads to secondary mitochondrial dysfunction
Diagnosis of Mitochondrial Disorders
hardymum: How common are misdiagnosis of mitochondrial diseases because they are fairly rare? How would this affect the patient in terms of their treatment?
Speaker_-_Dr__Sumit_Parikh: This is a difficult question to answer. It seems that mitochondrial disorders are not that rare - but we have had difficulty in diagnosing them. Also, the path to diagnosis is complex in that it requires many tests and there is no 'one' test that makes the diagnosis, but rather a person reviewing and interpreting the entire medical picture, or 'clinical story' and lab test results.
What we find too often is that when a patient has symptoms that a diagnosis has not been made for, mitochondrial disorders often get invoked as a diagnosis. We frequently see patients labeled with a mitochondrial disease diagnosis who in fact have something else, whether it be a genetic syndrome, or another medical issue like celiac or Lyme disease.
bobbyG: I have progressive autonomic neuropathy. My doctors have recently been considering doing a muscle biopsy to check for mitochondrial disease. However, they say that even if the test results come back positive for mitochondrial disease, there may be no change in treatment. If so, is it advisable to get the biopsy done?
Speaker_-_Dr__Sumit_Parikh: The muscle biopsy is a stepping-stone to diagnosis. A piece of muscle can get sent for a few or several hundred tests - and it is important to ensure that if mitochondrial testing is being done on muscle, all of the testing is done on it.
There is also an issue of whether a muscle specimen is frozen and sent to a mitochondrial lab for testing vs. obtained in a mitochondrial disease center and then mitochondria are harvested and tested while still living. We suspect that testing living mitochondria is more accurate though this type of biopsy requires a person to travel to Cleveland, Atlanta or San Diego.
Since that is not feasible for many patients, it is more important that ALL the necessary testing to evaluate for mitochondrial dysfunction is obtained the first time the biopsy is done. Far too often, we see that patients receive a muscle biopsy and only 1 or 2 tests are done on it.
It is true though that the muscle biopsy results do not directly affect our ability to provide prognosis or choose treatment if a person has mitochondrial disease. The muscle biopsy is better for helping find mitochondrial dysfunction and potentially directing genetic testing. It is also very useful for helping exclude other conditions that might be treated very differently than if one has mitochondrial disease.
julieB: Is it possible to have different results to muscle biopsies done at different times and by different labs?
Speaker_-_Dr__Sumit_Parikh: YES. This is unfortunately one of the challenges of the field. A piece of muscle, once obtained, can be handled very differently. In addition - each lab often has varied ways of running the testing.
This is one of the reasons why we do not 'rush' into obtaining muscle biopsies - and if we get one - we ensure that select labs are used for the testing.
handmedown: My child was diagnosed with autism. Would you recommend having him tested for a mitochondrial disease? What is the exact correlation between the two?
Speaker_-_Dr__Sumit_Parikh: Most patients who have autism have a genetic non-mitochondrial etiology for their symptoms.
Some patients with autism may have underlying metabolic disease (specifically mitochondrial disease) that may be worsening or bringing out autism and/or other symptoms.
We do not know which patients need to be screened and several groups are actively studying this issue. We suspect that patients with autism and other neurologic issues (seizures or mental retardation), GI dysfunction (chronic diarrhea) or regression after the age of 3 years or with illness may have underlying metabolic issues.
Symptoms of Mitochondrial Disorders
playingaround: What are some of the symptoms that would present themselves that doctors might suspect a mitochondrial disease?
Speaker_-_Dr__Sumit_Parikh: This is a very broad question. I will direct you to the Mitochondrial Medicine Society website (www.mitosoc.org), ‘Toolkit’ section, in-case you would like to read more.
blanketbaby: Is it common for someone with a mitochondrial disorder to show no outward sign that the disorder exists?
playdough: For a Complex I defect, what do you recommend for pain? My son’s pain varies from day to day as to what hurts and severity.
Speaker_-_Dr__Sumit_Parikh: Sadly, our approach to mitochondrial symptoms is the same whether or not someone has mitochondrial disease. Thus, a pain management expert should be able to help - even if they are not familiar with mitochondrial disease. They only need to make sure they do not use medications that have potential mitochondrial toxicity.
nervousmom: Can mitochondrial disease cause behavioral problems in my child?
Speaker_-_Dr__Sumit_Parikh: Possibly. We know that mitochondrial disorders can cause or worsen anxiety, depression, bipolar disease, and autism symptoms.
Pete: When damage to the brain occurs with a mitochondrial disease, is the brain permanently damaged?
Speaker_-_Dr__Sumit_Parikh: Sometimes :) It depends on how severe the brain injury is. We have had patients have some or complete recovery while others have not.
jheister: Is there a link between mitochondrial disease and crystals found in urine analysis? I read that when muscles break down during an illness / regression that crystals in the urine are an indication. Is that true?
Speaker_-_Dr__Sumit_Parikh: There are MANY causes of crystals in the urine - most being less esoteric than mitochondrial disease. The most common is calcium not being processed in the kidneys properly.
Treatment & Therapies
gold_mom: Is there a complete list somewhere that tells us what medications, IV fluids, anesthetics to avoid because of damage caused to mito?
Speaker_-_Dr__Sumit_Parikh: There is a list of both medications that are used for treatment and ones to avoid available in a Mitochondrial Medicine Society (www.mitosoc.org) paper, published in 2009, called the Modern Treatment of Mitochondrial Disease. More information can be found at the MMS website under the ‘Toolkit’ section.
dorcie: Could statins cause memory loss or muscle atrophy and are there any treatments?
Speaker_-_Dr__Sumit_Parikh: Statins - medications used to treat elevated cholesterol levels - interfere with CoQ10 synthesis. CoQ10 is crucial to mitochondrial function.
We suspect that statins may bring out problems in individuals who had underlying 'mild' or previously silent metabolic muscle disease (mitochondrial or other types).
As far as we know - the only treatment is stopping statins if they are bringing out symptoms and considering CoQ10 supplementation.
jpmorgan: For mitochondrial disease treatment, the levels of vitamins and minerals taken are very high. How does the doctor know when it is too high and instead of helping the body is actually toxic to the body?
Speaker_-_Dr__Sumit_Parikh: We typically follow blood levels of carnitine and leukocyte (white blood cell) levels of CoQ10 when utilizing high doses of these medications.
As a whole, mitochondrial medications have few side effects or toxicities. There is a theoretical concern though that there might be too much of a good thing.
UMDFOhio: I know there are different levels of absorption rates in different medications (CoQ10 for example) is there a specific thing to look for to tell what brand or type is best? My son was on a brand from Integrative Therapeutics but it is no longer available.
Speaker_-_Dr__Sumit_Parikh: There is a lot of debate about this - but Tishcon Corp. has obtained FDA approval for mitochondrial disease because their products have been shown to be bioavailable (available inside the cells) to the FDA's standards.
We understand that this formulation can be costly however, and that the supplement is not covered by insurance. Thus, we have our patients take the form that is most cost-feasible and monitor levels of CoQ in white blood cells to make sure they are getting enough.
plato: I have mitochondrial myopathy. Can massage help with symptoms, or can it hurt?
Speaker_-_Dr__Sumit_Parikh: As a whole - light or therapeutic massage is not harmful. Heavy or deep massage can lead to problems in some patients who turn over or injure their muscle too easily (they typically have elevated blood CPK levels - a marker of muscle turnover).
cranky: I have read somewhere that mito patients should not use aminoglycoside antibiotics. Is this true and if so, which antibiotics are these?
Speaker_-_Dr__Sumit_Parikh: We do try and avoid aminoglycoside antibiotics in patients with known mitochondrial disease. There is a large list of these and your physician(s) should know what these are, though some of them end in -mycin.
dorcie: My physician has increased my dosage of Lipitor® to 20mg daily M-F and 40mg on weekends for increased triglyceride levels, 300 from 246 in 3 months. I am concerned about memory loss. My total cholesterol levels are within normal levels. Should I be concerned about the increased dosage?
Speaker_-_Dr__Sumit_Parikh: We do not suspect statins of causing memory loss in metabolic patients.
Genetics of Mitochondrial Disorders
nervousmom: What are the genetics associated with Mitochondrial Disease? My father had it, I have it and my son has it. If I have more children, will they all have it? How about their children? Does it depend on the disorder or the severity?
Speaker_-_Dr__Sumit_Parikh: This is a very broad question that can have a very long answer.
In brief, mitochondria are made using nuclear DNA (nDNA) blueprints (from mom and dad) and a special DNA blueprint called mitochondrial DNA (mtDNA).
A person with mitochondrial disease may have a mutation (DNA typo) in either nDNA or mtDNA, though 80-90% of the time the problem is in nDNA.
Inheritance of DNA typos can vary in all diseases - including mitochondrial disease. In mitochondrial disease - just having a DNA mutation does not always mean a person will have symptoms.
If you know what DNA mutation is causing mitochondrial disease in your family - an appointment with a genetic counselor would be very helpful.
If a specific DNA diagnosis has not been made, you may want to see a geneticist who specializes in mitochondrial diseases.
jheister: If the son of a mother with mitochondrial disease shows symptoms at birth, it is most likely Primary (genetic) mitochondrial disease? If a daughter of the same mother also shows symptoms (but at age 7) does that mean the father must also have a genetic mutation linked to mitochondrial disease? What type of blood tests would help identify those genes?
Speaker_-_Dr__Sumit_Parikh: It turns out that even in families with the same DNA mutation impairing mitochondrial function (maternally inherited mitochondrial DNA mutations OR nuclear DNA mutations from either mom or dad), each family member may have relatively different symptoms, vastly different severity of symptoms and different ages of onset.
Thus in your case, it is possible it is still the same problem affecting all 3 of you. A geneticist or neurogeneticist with expertise in mitochondrial genetics can help direct you to the correct test - though our ability to make a genetic diagnosis is still limited.
nervousmom: Through my reading, it seems that most of these disorders are passed on through the mother. Is this true?
Speaker_-_Dr__Sumit_Parikh: There is an earlier posting from today that briefly reviews the genetics of mitochondrial disease.
The majority of mitochondrial disorders are inherited or due to new problems in regular (nuclear) DNA (from either mom or dad). Only sometimes is the mitochondrial disorder from maternally inherited mitochondrial DNA disease.
hadto: What difference does genetic testing make when planning for children? Are there some disorders that doctors would recommend not having children? Are there some disorders that can be "fixed" before a child is born if detected in-vitro?
Speaker_-_Dr__Sumit_Parikh: The value of a genetic (DNA) diagnosis is so that the geneticist can discuss with you prognosis (less so for mitochondrial diseases), provide proper preventative care, and guide you as to what the recurrence risk is of this problem happening in any children you have. This may lead to pre-pregnancy or pregnancy related testing.
We do not have an in-vitro fix though for mitochondrial DNA mutations, a mitochondrial DNA 'transplant' is being studied.
Immunizations and Mitochondrial Disorders
nervousmom: I have heard and read that immunizations can be harmful to children with mito disorders. My pediatrician still wants my child to have them. I am undecided. What are your thoughts?
Speaker_-_Dr__Sumit_Parikh: There is no clear evidence that immunizations themselves hurt mitochondrial or metabolic patients.
Medical stress (fever, dehydration, illness, revving up the immune-system) may bring-out or worsen metabolic disorders. Thus, there have been some patients where the fever after an immunization led to symptom onset or worsening. In these individuals - it was not directly the immunization that led to issues.
We recommend that our patients receive immunizations. If they are sensitive to declining during medical stress - spacing out immunizations and tight fever-control may help (but this type of approach is not based in medical science and what physicians call 'anecdotal experience').
Research: Chronic Fatigue and Mitochondrial Disorder
jollymolly: Is there an association between Chronic Fatigue and Mitochondrial Diseases?
Speaker_-_Dr__Sumit_Parikh: The diagnosis of 'chronic fatigue syndrome' is an evolving one. It was recently found that some of these patients may have an underlying retro-viral infection - though more research is still needed to better determine whether this is true.
It is possible that some patients with chronic fatigue have mitochondrial dysfunction - but typically isolated fatigue (and associated issues of chronic pain) are not the only symptoms in mitochondrial disease.
A colleague, Dr. John Shoffner, in Atlanta, is performing research to study the possibility of mitochondrial issues in patients with chronic fatigue syndrome.
Cleveland_Clinic_Host: I'm sorry to say that our time with Dr. Sumit Parikh is now over. Thank you again Dr. Parikh for taking the time to answer our questions about Mitochondrial Diseases.
Speaker_-_Dr__Sumit_Parikh: Thank you so much for joining us today. I appreciate the opportunity in helping answer some of your questions. Have a great day. - Sumit
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