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Mitochondrial Disease -- Another Hopeless Disease

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Mitochondrial Diseases

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What they are, how to learn more

 

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How We Discovered Mitochondrial Disease in our Family

Why do we have this page? We have seven kids who have been diagnosed with a Complex I defect of the mitochondria. During the first three years of our effort's to find out what was "wrong" with our most affected son, Tim, we were met with constant frustration. It went something like this:

• Tim, born in October of 1994, full term, had a severe case of hyaline membrane disease, requiring NICU care with respirator and liquid surfactant. The neonatologists were mystified as to why this occurred. Luckily, he survived.
• Immediately after bringing Tim home from NICU, we noted he was very "floppy", had poor sucking, and needed to be handled very cautiously.
• He had numerous episodes of sudden dehydration.
• At age 8 months, he began physical, oral/motor and speech therapies. Feeding issues resulted in constant attention to weight gain (Tim is very low weight).
• At age 14 months, his physical therapist agreed with my observation that something more was going on with Tim than simple developmental delay.
• During this time, our pediatrician, who was a close family friend, allowed us to pursue investigation, even referring us to a geneticist, while also saying he thought everything was fine.
• At 18 months, Tim was diagnosed with a severe to profound bilateral sensorineural hearing loss, meaning he was deaf.
• At age 2, we went to Mayo Clinic, where all known disorders were ruled out, and the suggestion of mitochondrial disease was made. This was something we suspected through our own "internet investigation" and the use of the OMIM database.
• At age 3, a fluctuating hearing loss was confirmed, and Tim was enrolled in a full time hearing impaired preschool, with one on one support for his physical needs.
• More hospitalizations for dehydration occurred.
• In January of 1998, we chose a new pediatrician, who immediately referred us to Atlanta (Dr. John Shoffner) for a mitochondrial muscle biopsy.
• September, 1998: a Complex I and IV mitochondrial defect was confirmed.

What is Mitochondrial Disease?
The United Mitochondrial Disease Foundation (linked on this page) offers this analogy to help you understand (and me, too!) If your power goes out in your home, your food spoils, your heating/air conditioning does not work, and you're left in darkness. You call your local powersupplier to report the problem.
The Mitochondria--the part of the cell responsible for energy production--is very much like the power supplier that provides energy to your home. If the mitochondria (power supplier) is defective, your body cannot function as it should. The brain becomes impaired, muscles start to twitch spastically and weaken, the heart does not pump correctly, vision becomes impaired and the list can go on. For many chldren and adults with mitochondrial disease, this is exactly what they experience.
To give you a more "scientific explanation", look at this picture of a mitochondrian, showing you the basic structure of a mitochondrian, which are present in every cell in our bodies:
 

Mitochondria are the powerhouses of the human cell; they convert the energy stored in sugars and fats into adenosine triphosphate (ATP), the essential energy molecule of all animals. This energy production is carried out on a complex folded inner membrane of the mitochondria (see the picture above). Every muscle cell is filled with mitochondria, combinging sugars or fats with oxygen to yield water and ATP. Without this ATP, we would die, having no "power" left. Mitochondrial cytopathies have a diverse range of symptoms, and span many (all) organ systems. There is such a large number of biochemical and genetic defects, that currently a predictable clinical course does not exist. Using the description above, the analogy of a power supplier not supplying enough energy is a good one. The mitochondrian in the above picture is only one of many in your cells. The reason people manifest with SO many different problems is based on the percentage of "bad" mitochondria that get assigned to that part of the body. In our own family, some kids obviously have a higher percentage of bad mitochondria in their muscles than some of their siblings, while others have more brain (neurological) problems. This chart shows you a basic idea of how this can happen. Keep in mind that men do not contribute mitochondria, but that does not mean that only Mom causes mito disease, as there can be mutations.

 

Here's the simplest way to explain what happens. The food we eat gets broken down and assigned in various fashion. The fats and sugars go through processing, and there's quite a bit involved in this. If you get into this stuff more, you'll hear all about the respiratory chain and ATP, which is the end result, or energy. The mitochondria in a cell have to go through five "complexes" to create energy. An error in any of those complexes is bad, but obviously there can be varying degrees of how big the error is, and where it occurs in the energy making process. Mitochondria are responsible for producing most of the energy that's needed for our cells to function. In fact, they provide such an important source of energy that a typical human cell contains hundreds of them. A mitochondrial disease can shut down some or all the mitochondria, cutting off this essential energy supply. Because muscle cells and nerve cells have especially high energy needs, muscular and neurological problems are common features of mitochondrial disease. MDA uses this picture to help illustrate:

 

Current Diagnosis Status in Our Family
Tim, now age 7, is the only one with a somewhat "well defined" diagnosis, which is currently this: Complex I defect in muscle with negative mtDNA southern blot, negative SSCP and sequencing of mtDNA (Complex I, Complex V, tRNAs, rRNAs). His symptoms included: Dicarboxylic aciduria; abnormal enamel development; moderate retrognathia; bilateral fluctuating hearing loss; motor and language developmental delays. And I probably forgot something! Our daughter Annie, almost 10 years old, has just had her muscle biopsy done, so we will hopefully have results from that very soon. I may also soon be tested, as I show many signs of the adult onset form of the disease.

 

“An observant parent’s evidence may be disproved but should never be ignored” —Lancet 1:688, 1951, Anonymous

Exceptional Parent magazine's editor, Dr. Rick Rader, offered this in his column recently, and suggested that perhaps parents with "reluctant" physicians be sent a copy before their next appointment. I hope it helps some parent to get the help with seeking diagnosis that betters the quality of life for some family. The picture, in Dr. Rader's words: "They say a picture is worth a thousand words, and that’s what I am normally allotted for my monthly Editor’s Desk. When I was a med student, I did a rotation at London’s famed Hospital for Sick Children at Great Ormond Street. At one of the nurses’ stations, where the students would stock up on Cadbury’s chocolate taken from patients’ rooms and read charts, there was a crude wood sign with the quote that appears below. On the last day of my rotation I scribbled it down on the back of a wrapper from a Fruit and Nut Bar, and have kept it ever since." I dont' know about you, but I think I would like Dr. Rader very much!

 

When Should I Suspect Mitochondrial Disease?

As you read this, it may be nothing like what your child has. When should you investigate mitochondrial disease in your child, or even in yourself? Here are some "Rules of Thumb" of when to think mitochondria:
 

1. A "common disease" (i.e. autism, cerebral palsy, lots of others) has atypical features that set it apart from the pack.
2. Three or more organ systems are involved.
3. Recurrent setbacks or flares in a chronic disease occur with infections.
4. Credit for above "rules of thumb" to Mitochondrial News, Spring 2000 Issue by Dr. Robert K. Navaiaux.

 

Problems That May Be Associated with Mitochondrial Cytopathies

 

Organ Systems	Possible Problems
Brain	developmental delays, mental retardation, dementia, seizures, neuro-psychiatric disturbances, atypical cerebral palsy, migraines, strokes
Nerves	weakness (which may be intermittent), neuropathic pain, absent reflexes, dysautonomia, gastrointestinal problems (ge reflux, dysmotility, diarrhea, irritable bowel syndrome, constipation, pseudo-obstruction), fainting, absent or excessive sweating resulting in temperature regulation problems
Muscles	weakness, hypotonia, cramping, muscle pain
Kidneys	renal tubular acidosis or wasting resulting in loss of protein, magnesium, phosphorous, calcium and other electrolytes.
Heart	cardiac conduction defects (heart blocks), cardiomyopathy
Liver	hypoglycemia (low blood sugar), liver failure
Eyes	visual loss and blindness
Ears	hearing loss and deafness
Pancreas and Other Glands	diabetes and exocrine pancreatic failure (inability to make digestive enzymes), parathyroid failure (low calcium)
Systemic	failure to gain weight, short stature, fatigue, respiratory problems including intermittent air hunger, vomitting

Taken from Mitochondrial News, Fall 1997 Issue by Bruce H. Cohen, M.D.

 

When & Where to Get a Diagnosis

 

Diagnosis of mitochondrial myopathies has been done only since about 1988. Few centers in the country are equipped to make an ACCURATE diagnosis! Be sure that before undergoing a muscle biopsy (the most common way to make the diagnosis) that the center you are using can read the biopsy FRESH, not frozen and shipped elsewhere. Many families have had the frustrating experience of having a biopsy done and read as negative for mitochondrial disease, only to have it redone at a center where the biopsy is read fresh and then the disease is confirmed. You don't need to go through it twice!

Though we live in northern IL, we opted to go to Scottish Rite Children's Medical Center in Atlanta, GA (now known as Children's Healthcare of Atlanta). Our reading had led us to believe that Dr. John Shoffner was the leading man in this field. We wanted an accurate diagnosis. Keep in mind that the diagnosis and treatment of mitochondrial disease are two totally separate issues. While we got our diagnosis from Atlanta, we receive all of Tim's care in our home city. We are lucky to have a pediatrician who admits it when he doesn't know the answer to something, but is always willing to seek it out. He is also quick to conference with the rest of Tim's team, which includes a local geneticist, a pulmonologist, a cardiologist, an audiologist, a gastroenterologist, and a neurologist. The neurologist is an important member of the team, and we are lucky to have Dr. Ammar Katerji in that role. He came to our city after having been in a city where the early research into mitochondrial disorders was done, and thus knows many of the important researchers. The intense interest of Tim's team of physicians has given us the feeling that we are doing all that we can to maximize Tim's health and to extend his life.

SO--go where you must to get an accurate diagnosis, then interview doctors until you find those who are interested and willing to learn! The best way we have found to locate doctors is to contact the UMDF and ask them for guidance. If there is a support group in your area, they may send you there.
 
 

 

Diagnostic Testing for Mitochondrial Disease
 

1. Blood for mtDNA (PCR and Southern)
2. Blood and CSF for Lactate and Pyruvate, or Brain MR Spectroscopy
3. Urine Organic Acids (by GC/MS)
4. Plasma and Urine Amino Acids
5. Blood and Urine Carnitine
6. Brain MRI
7. Muscle Biopsy and Skin Biopsy, Neuropathology and Electron Microscopy, Mitochondrial Electron Transport Studies, Fresh (coupled) mitochondrial Polarography, Muscle mtDNA (PCR and Southern)

Taken from Mitochondrial News, Spring 2000 Issue, by Dr. Robert K. Naviaux

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Carnitine: An essential thing to check in children with low muscle tone, frequent infections, slow weight gain.
Carnitine plays an important role in cellular energy metabolism!The mitochondria is the "furnace" of the cell. Fatty acids (fuel) must bind with carnitine to enter the mitochondria. Once inside, fatty acids are burned for energy. Carnitine then binds with the toxic waste by-products of metabolism, removing them from the mitochondria. The inner mitochondrial membrane is impermeable to fatty acids. Transport of fatty acids across this membrane can occur only when the fatty acids are attached to carnitine. Toxic waste products resulting from energy production are removed from the mitochondria by binding to carnitine. If they are not removed, toxic build-up occurs. Carnitine is a small molecule found in animal foods. There is little in a strictly vegetarian diet. This transport via the carnitine is the first step in turning fat into energy for driving muscle contraction or nerve cell firing. When carnitine is in short supply production of ATP is slowed. Only the L (levo) form of carnitine is safe for humans; the D form, which does not occur in nature, can be toxic.
Carnitine deficiency should be suspected if the any of the following are present:
 

 

Symptoms of Carnitine Deficiency

Very poor muscle tone and coordination

Chronic vomiting

Runs a chronic fever

Vomits after exercise

Severe feeding problems

Little weight gain, and/or weight loss

Lethargy and unusual weakness

Recurring, stubborn infections

Flu-like symptoms

Increased seizures

 

Carnitine Deficiency is an often missed diagnosis, and can exist independently of mitochondrial disease. If you have a primary carnitine deficiency, treatment with Carnitor or another reliable replacement will bring about miraculous results. Check these links for more information on what carnitine is, and how it can be replaced in those with deficiencies.

Carnitine Defiency Syndromes: NORDFrom the National Organization for Rare Disorders

Mitochondrial disorders often have a carnitine deficiency along with them. Read up on the replacement supplement Carnitor at Sigma Tau's web page.

Tishcon Corp. makes a a very stable Carnitine that was developed and patented by Sigma-Tau. Their products include L-Carnitine combined with Co-enzyme Q10, discussed below.

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Feeding

For children with weight gain issues, supplemental feeding becomes important. We use Pediasure to keep Tim's weight up. He requires six cans daily, which is a lot to drink. We used an NG tube to assist him. In the summer of 1999 he had a gastrostomy tube put in, which is a permanent "opening" in his stomach through which  we can do feedings. During that surgery he also had a venous port implanted. He lost this handy device to a staph infection in late 2000, but we may opt to replace it soon. It was under his skin, on a lower rib, and is inserted directly via catheter to one of his neck veins. That made blood draws and I.V. placements much easier.

Currently, Dr. Shoffner has asked us to implement a trial of a diet with reduced long chain fatty acid content. Recent data indicates that many patients with Complex I defects have secondary defects in long chain fatty acid metabolism. This can further inhibit oxidative phosphorylation.
 

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Dehydration

Because Tim dehydrates VERY rapidly, we get him to the hospital at the first sign of serious illness. Vomitting means he needs an IV WITH DEXTROSE as soon as possible. This addition of fluids and sugar helps him with that flaw in the energy cycle. We have seen him come back many times from the brink of death to his normal, albeight slightly frail looking, bubbly self. For a year and a half he had an implanted venous port, which allowed for immediate IV access and avoided the need to find any other veins, as his collapse so easily. Unfortunately, due to the refusal of a home care nurse to use aseptic procedure, this central line developed a staph infection that resulted in the line having to be pulled. When it is replaced in the near future, you can be sure that no nurse will access our son without adhering to my strict criteria, as spelled out by the Infectious Disease Specialist.
 

 

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Co-Enzyme Q10
Coenzyme Q10 is a very hyped thing right now. You can get it in face cremes, power bars, and numerous vitamins. But for those with mitochondrial disease, it is considered as a generally accepted effective therapy, although it may not be effective for an individual patient. It is usually prescribed is a dose range of 5-15mg/kg/day, not to exceed 200mg daily. It is important that you get your CoQ10 from a trustworthy source, not from an ad in a magazine. Generally, chain providers (such as Walgreens, Osco, etc.) will have forms of CoQ10 available without additives. Check with your doctor before beginning this therapy, and tell them the full ingredient list on the label. There are a couple of trustworthy providers in the links at the end of this page.

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Issues of Anesthesia in Mitochondrial Cytopathies
The full text of this article, written by Drs. Bruce Cohen, John Shoffner, and Glenn DeBoer is available online. But here, in a summary, are some things to keep in mind when a person with mito disease is going to have anesthesia:
 

 

1. The vast majority of patients with mitochondrial cytopathies have an uneventful surgery and anesthesia.
2. Patients rarely experience a complication with a simple elective surgical procedure such as a muscle biopsy or gastrostomy tube placement.
3. There are limited reports describing adverse events and outcomes in patients with mitochondrial diseases.
4. Patients with mito disease, on average, are "sicker" than an unaffected person undergoing surgery.
5. Patients with mito disease are at greater risk than unaffected people for side effects of some medications.
6. Adverse events reported include new neurologic problems such as a stroke, worsening of the overall neurologic status, respiratory difficulties, seizures, cardiac arrhythmias, prolonged coma and death.
7. Hypotonia (low muscle tone), bulbar dysfunction (weakness of the muscles that protect the airway) and relatively poor ventilatory function (decreased ability to breathe deeply and cough) are common in patients with mito diseases and pose an increased risk for perioperative pneumonia.
8. Malignant Hyperthermia (MH) is a life threatening, inherited syndrome triggered by potent inhalational anesthetic agents and/or depolarizing muscle relaxants. Muscle disease is ONE risk factor for MH. Many patients with mito disease sometimes have an associated disease that places them at potential risk for MH.
9. The risk of respiratory failure and worsening of neurologic function is often noted in patients with mito disease after "stressful" illnesses, including infections such as routine viral illnesses or pneumonia. Infections can occur with surgery, even minor surgeries.
10. Patients with heart rhythm problems are at risk for severe heart electrical conduction blocks, which can lead to death. Isoflurane may be a preferred inhalational agent as opposed to Halothane, because Isoflurane causes less disturbances in heart rhythms.
11. Although spinal anesthesia is safe, it should be used with extra caution in patients with neuropathies or myopathies, because of possible deterious effects on blood pressure and respiratory function.

Links for further learning

Use these links to know more.

Rare genetic diseases in childrenThere are far too many of them! Mitochondrial disease are only one of those discussed at this site.

The United Mitochondrial Disease Foundation It is vital for all affected by mitochondrial disease to register with the UMDF! The information they compile in their database will help us share information that can help all our loved ones.

MITOMAP: A human mitochondrial genome database This will make you wish you had paid betterattention to biology classes! If you want to do some serious learning of the "whys" of mito disease, this should keep you busy.

Mitochondrial Disordersmore links to follow, many personal pages.

MDA Ask the Experts' on mitochondrial myopathy. Muscular Dystrophy Association covers mitochondrial myopathy under the umbrella of their excellent research. Besides information on the diseases, they have tons of practical information, including little "help hints" for living with neuromuscular disease. Their brochure for parents is excellent. I have used their information for educating our school personnel. It is written in a friendly, understandable format.

Mitochondrial Disease and Hearing LossHearing loss often occurs as an additional symptom in a number of syndromic diseases caused by mitochondrial DNA defects. It is common for mitochondrial mutations  to give rise to different pheonotypes in different families or patients.

Metabolic Response Modifiers (MRM)MRM is a supplement guide offering quality health supplements. They also support the UMDF by donating a portion of all sales to the United Mitochondrial Disease Foundation. They have L-Carnitine in liquid and tablets; CoQ-10 with enhanced absorption, and vegeterian capsules, and lots of other products. Call for a catalogue (800-984-6296) or shop online at www.bestbuyhealth.com and insert UMDF as password for a discount.

 

Vitaline FormulasThis is another provider of CoQ10, and they offer a chewable form, which has been the only way we got our kids to take it!

 

The Children's Mitochondrial Disease Network

Tomato Face FoodsWhen the diagnosis of a Mitochondrial Disorder necessitated that the founder of the company adapt a fat free diet (not applicable to all persons with mito disease!), she made her own great tasting spaghetti sauce. With every purchase of a Tomato Face Foods product, a portion of the proceeds is donated to the UMDF to help promote research, awareness and hope. This is a MEATLESS "meat" sauce, and I've tried it, and encourage you to do so, too!

 

UMDF "Awareness Pins". These are the same kind of pins that other non-profit agencies use to create awareness and raise funds. They are great conversational pieces, people get curious about these pins and will ask "what's that for?". There is a minimum donation of $5 plus shipping. Find out more by contacting the Southern California Chapter of UMDF by email.

 

55 North Bath and Body Shop is located at 55 North Baldwin Avenue in Sierra Madre, CA. Owner Carol Wehling is donating a portion of her sales each quarter to the So. CA Chapter UMDF. She carries an assortment of men's & women's specialty items, such as fine soaps, lotions, candles, sleepwear, slippers and much, much more! They make gift baskets, too, large or small and ship anywhere in the U.S. Perfect for holidays, anniversaries, birthdays, or anytime. Call Carol at 626-355-8500 and remember to tell her you are with the UMDF!

 

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Other Stuff

We've been blessed by lots of folks who have helped us care for Tim. Here's some links to organizations we have benefitted from:

• Project Linus: This volunteer group consists of (mostly) ladies who make blankets for chronically ill children. Tim got his first blanket back a few years ago, choosing a small blue one with animals on it. His little brother eventually claimed it for his own, so Tim was given a new one. This time he chose a bright Joe Boxer pattern. He has loved them both, and is very proud of them. We truly appreciate the love that goes into these blankets. If you can sew at all, consider contributing by visiting their website. You will be directed to a nearby hospital who needs you.
• Make A Wish Foundation of Northern Illinois: Mitochondrial Encephalomyopathy is a life threatening illness, and Make A Wish exists to help kids who face such a illness with one very special wish. Tim chose to go to Universal Studios in Orlando, FL (Disney in Orlando is the Number 1 wish). He wanted to slime his older brother, Steve, on a Nickelodeon game show. It was a great trip, made even better by our stay at:
• Give Kids the World: There is no way to describe this magnificent home away from home in Orlando. It is like living in a theme park. I never even knew such a place existed. I cannot say enough about the beauty of the place. Pictures coming soon, along with a bigger description. All the food there is provided most generously by:
• Perkins Restaurants: Good food, great organization. Each there whenever you can, and always say a kind word to the manager about the support of Give Kids the World Village. They will be glad you did.
• Rockford Register Star: Our hometown newspaper has been there to photograph Tim's visit from:
• City of Rockford Police: It was Sgt. David Hooks (of National Enquirer fame!) who got a group of city police, fire, and ambulance folks together to give Tim a visit from real life "Rescue Heroes". (Click here to see a pic and more on that.) He had spent his 5th birthday in the hospital and wanted simply a visit from a real policeman. Dave and his friends went far beyond that. Live at 5 broadcast from our front yard. It was VERY cool, and Tim still talks about it. Pictures coming soon.
• WZOK Radio: Steve Shannon and Stef Troy are the morning hosts of this, 97.5FM in Rockford, IL. Steve was once submerged in water for some ungodly long period of time (I forget exactly!) to benefit MDA. To see a pic of them with Danny, click here.  We are grateful for their many efforts on behalf of local charities.
• MDA: I know, I list them as a resource, but summer camp rules around here. There are usually at least a few pics of the kids at camp, and you can check if there are by a click here.

   

• The best form of support comes from those who have "been there, done that" OR are "getting there, trying that". To that end, there is a listserv, which is a daily potpourri of info and sharing. Just click here to get started. I would strongly recommend subscribing to the DIGEST version, or you will find yourself swamped with emails!

Mitoldies is an online support group for adults with Mitochondrial Disease and their caretakers. While I have not yet participated in this group, I do know you can check them out on the web, or email them.

 

Did you know....If you or anyone you know donates to the UNITED WAY, you can specify which charity you would like the donation to go to. The UMDF has a United Way number and all you have to do is give this to them when you make a donation.

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