Showing 61 to 80 of 437      First | Prev | 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 | Next | Last

Q: My 2 1/2 year old daughter was diagnosed about a year ago with mitochondrial disease, complex IV, COX deficiency. She has intractable seizures. She has been on most of the available medications and is currently on the ketogenic diet and has been for about 6 weeks. She had a very severe reaction to the intiation of the diet, including vomiting, diarrhea and extreme lethargy. She is on a 4:1:1 ratio. She had a complete amino acid and organic acid profile done previously that did not show any problems. She is eating again, but has not returned to normal cognitively and her seizures have not decreased. Her primary seizure type is tonic-clonic, but she appears to just sit and stare most of the day since the initiation of the diet. I do not think she is seizing during these times because eventually she will respond to her name, but very slowly. We have found that the more fluids she consumes the better she seems to feel and the less seizures she has. Everytime she is admitted to the hospital and put on IV fluids her seizures stop. If we give her a lot to drink during the day and her diapers are really wet her seizures are decreased later that day and the next. Her seizures stopped for an entire week when we went to visit family out of state. She went swimming 2-3 times a day everyday. While she was in the pool she was constantly drinking the pool water. Is there any type of relationship between fluid intake and reduced seizures in kids with mitochondrial disease?

A: I am sorry to hear about your daughter. The reaction your daughter had with diet initiation is not uncommon. This is why we like to introduce the diet while the patient is in the hospital. Is your daughter taking the ketocal formula or is the diet non-ketocal? We have found that depending on the patient and the beta hydroxybutyrate level achieved, various diet ratios are tolerated depending on the particular patient.
What I mean is that for one patient, a 3:1 diet works best, for another, a 3.5:1 diet works best and for others, a 4:1 ratio diet works best.
This needs to be considered, because we have found that one ratio does not fit all. The type of lipid used can also affect the toleration of the diet. Some of our patients cannot handle microlipid well. Toleration of the diet often depends on what seizure medications are used as well. For instance, enzyme inducing drugs will often increase the triglyceride levels. We have also found that extremely high beta hydroxybutyrate levels can adversely affect cognition and awareness. The level of beta hydroxybutyrate inducing these changes varies between patients. We usually try to aim for beta hydroxybutyrate about 40-60. Some centers restrict fluids but we do not, as this does not seem to help. So, fluids are okay to give. I don't know what her beta level is when she gets IV fluids. My guess is that her beta is really high and you are reducing the concentration of them with added fluids or you are correcting a dehydrated state. We have seen this in some of our patients as well.
When the beta gets really high, patients can become irritable and some have increased vomiting and seizures. We do many labs during the initial part of the diet so we understand how a patient individual biochemistry is altered by the diet. I would think this might be helpful to your daughter.

Answered by: Russell Saneto, DO, PhD

(back to top)



Q: My daughter was diagnosed with MELAS in 2004. She had a severe migraine and a stroke. It took months to figure it out with the help of a genetics doctor. She has had several bouts with migraines that put her in the hospital for pain treatments. She also has muscle twitches which are little seizures. She is only 57 lbs. and is 18 years old. She does take a vitamin cocktail. I was wondering if there is a certin diet she should follow that might help her feel better and put on a few pounds. She does seem to like eating more carbs then protein. She is a very picky eater and doesn't like much. Basically she is anorexic. She has a great neurologist but she doesn't really know much about MELAS.

A: In regards to your daughter with MELAS, I am concerned by her poor growth and nutrition status. If you have not met with a gastroenterologist and nutritionist, I would see if this is possible. If she is not growing despite adequate 'age-appropriate' calories, she may need someone to determine her basal metabolic rate and see how many calories she actually needs. Many patients with mitochondrial disease have a higher metabolic rate and require more calories.
If she is not able to get enough calories into her, then ways to ameliorate that problem should be looked into, including, but not limited to night time G-tube feedings and calorie supplementation. If she is very picky and 'anorexic' as you imply in that she does not like to eat much - the G-tube mediated calorie supplementation is most likely needed.
In regards to diet - unless she has an identified problem in metabolizing fats or proteins (seen on amino/organic acid and acylcarnitine testing) OR if she does not get ill after ingesting a specific category of food (protein/carbohydrate/fat) - then there are no firm dietary changes that a MELAS patient needs. Some metabolic physicians do recommend a trial of small frequent well-balanced meals (5/day instead of typical 3) and a bedtime snack of corn starch to prevent prolonged fasting and secondary body catabolism.
Lastly, in regards to the cocktail - a trial of Arginine should be considered (see MELAS Arginine therapy, in Mitochondrion 2007, by Dr. Koga et al).

Answered by: Sumit Parikh, MD

(back to top)



Q: I have a 2 1/2 year old son with a Complex I mitochondrial disorder. A month after his second birthday he started experiencing episodes of vomiting. I do not think that it is cyclic vomiting syndrome, in that he only will vomit once. One day he will vomit without warning, it just pours out of his mouth with no gagging. Then for the next week he has a very poor appetite. He will start to regain his appetite and then he vomits again. When he vomits he becomes pale in color. We have had him to the doctor and they are unsure what it is. They did a blood test and nothing has showed up. Another thing that has been happening which may or may not be related is he gets a rash only on his face. It starts out as a red dot, raised into a white head and then disappears. He is not complaining of any itchiness and we are also unsure of the cause. Could the rash and vomiting be related to his diagnosis? Another question that I have is that my husband and I would like to have another child, they told us that there was a 25% chance of having another child with mitochondrial disorder. If I start taking the mito supplements prior to and during my pregnancy will it be beneficial in preventing another child with mitochondrial disorder or will it improve the childs outcome, so that they may also have a mild case as my son does?

A: I am sorry to hear about your son's episodes of vomiting. Yes, such episodes may occur in children affected by mitochondrial disease, even if a definite cyclic pattern is not present. Rashes may also occur, so it is possible that these symptoms are indeed related to his underlying diagnosis of complex I deficiency. Sometimes children who have mitochondrial disease experience a variety of symptoms related to the function of the autonomic nervous system (which functions to keep our bodies in equilibrium). Such symptoms include gastroesophageal reflux, a rapid heart rate, abnormal body temperature regulation, colonic dysmotility, migraine headaches, and blotchy rashes. In my experience, sometimes treatment with an antihistamine (e.g. cyproheptadine) can help alleviate symptoms in some patients. From what you say about the recurrence risk you were given, your doctor likely thinks that your son has inherited an autosomal recessive form of mitochondrial disease. In such cases, an affected child inherits an abnormal copy of a gene from each parent. The risk for having another affected child is 25% in autosomal recessive conditions, regardless of taking supplements or medications. In general, siblings who are affected by an autosomal recessive condition are likely to have similar features, although numerous exceptions exist. I think it would be worthwhile to meet with a prenatal genetic counselor to discuss inheritance in more detail. I would not expect taking mitochondrial supplements prenatally to change the outcome, although it is important to take the usual recommended vitamins as prescribed by your obstetrician.

Answered by: Greg Enns, MB, ChB

(back to top)



Q: My son's seizures have increased dramatically. Does this indicate this is progressing or just maybe a different therapy approach? My son underwent muscle and skin biopsy in 2005 which were normal but clinical and other blood work up ( lacic acid elevated) indicated some kind of mitochondrial disorder, but undefined biochemically. His seizures increased dramatically and his breathing with breath-holding followed by shaking and extremities jerking have been progressively worse. Should we follow up with our mito doctor to see if we can do anything different to find the optimal therapy for it? I know there is no cure, but is it worth to see if we can change therapy?

A: I am really sorry that your son has seizures. What we know about epilepsy is that seizures are unpredictable; seizures have no time scale and can erupt at any time. You are very correct in thinking that the events your son is having need to be investigated. The first priority is to make sure they are actual seizures; that is, the events are driven by abnormal brain activity. This may even require to be admitted to a Video-EEG room in the hospital and undergo examination for a few days.
Hopefully, several events will be captured and then can be analyzed to see if they were actual seizure events. Then, working with an epileptologist, try to sort out which medications might be best to control these events. The medication part may take awhile to sort out but it is necessary to optimize seizure control and medication side effect profile. Unfortunately, this is usually a trial and error process. Each child is so individual that we need to see just what drugs and their dosing will achieve in a particular child. Since your son has some symptoms of having a mitochondrial disease, this should be mentioned to the epileptologist as well.
If these events are not correlated with the abnormality on EEG, then likely they are not cerebral seizures. Our seizure medications really do not work well for these non-cerebral events. But, it is critical to know if the events are or are not cerebral seizures.

Answered by: Russell Saneto, DO, PhD

(back to top)



Q: Our 3 year old daughter was diagnosed with Complex I and III defects in January. She has intractible seizures (since 9 months old) and developmental delay (she's seems to be doing very well despite her medical issues). The mito DNA sequencing showed no mutations, which means she has an autosomal recessive inheritance pattern from the nuclear DNA. We have an older daughter who is healthy, but are interested in having another child. I know there is a 1 in 4 chance for our next child to inherit the mutation. My question is, if our next child would inherit the mutation, would the symptoms and severity of the disease be the same as our daughter's or could there be other symptoms present with more or less severity? Would the actual nuclear DNA mutations also be the same (ie- same deletion, same insertion, base pair change)?

A: I am glad to hear your daughter is doing well. From what you mention, it sounds like your daughter almost certainly has an autosomal recessive condition. I say "almost certain" because I don't know the exact details and assume the enzyme studies and mtDNA sequencing were done on a muscle biopsy and the DNA was fully sequenced, rather than screened. Assuming that is correct, then siblings with the same autosomal recessive disease usually have similar symptoms and similar severity of disease. However, the disease gene is often not 100% responsible for determining the severity of a disease. Other genes can impact on this and so can the "environment", particularly things like infections, for example at what age and how severely a child may have flu or gastrointestinal disease, how well nourished they are, etc. Occasionally, affected siblings with autosomal recessive disease can show substantial differences, and we have seen that in some children with mtDNA depletion. However, as a general rule, the symptoms and severity are likely to be similar. If a second child was affected then we would expect them to have inherited exactly the same nuclear DNA mutations as the first child.

Answered by: David R. Thorburn, PhD

(back to top)



Q: My daughter has been suspected of having Mitochondrial Myopathy; we just had a second opinion from the local MDA and they said the same. Besides the normal blood work, or biopsy, is there a specific genetic test we can do to confirm this? This disorder seems so different with each child and all the research I do she fits in some cases and not in others. Is there a test we can do for an absolute yes or no?

A: Unfortunately, there is no specific test for mitochondrial disease. Certain patients show a very specific clinical picture and this might be typical of a certain type of mitochondrial disease. Under these circumstances then a genetic test may be best. For many children however, a range of tests is necessary.

Answered by: Douglass M. Turnbull, MD, PhD

(back to top)



Q: Can a person with a mitochondrial disease be an organ donor?

A: There are no formal/studied guidelines. We would suspect if there is a mitochondrial DNA mutation that is known - that each organ's mitochondria harbor these mutations - thus the recipient would be receiving an organ with a certain % of unhealthy mitochondria. In this circumstance, our group advises against using the organs as donor tissue. If there is a nuclear DNA mutation - the answer is not as straight forward.  If there is a mutation causing mitochondrial depletion, then this organ has 'lived' its entire life without enough mitochondria and is likely functionally 'older' than the donor's chronological age.  In this situation - using the tissue is not advisable.
Other situations would be determined on a case-by-case basis.

Answered by: Sumit Parikh, MD

(back to top)



Q: Is there any new research on Mito & the use of cord blood ? My daughter (age 29) is due to have a baby in Dec. 2007. She is looking into having the cord blood saved & stored. She asked if it could possibly help me with my mito situation. I have no idea if cord blood might be beneficial for mito patients. I read a previous cord blood Q&A posting on “ask the mito doc” but was told it was a couple of years old.

A: Two mito doc responders answered this question: David Thorburn, PhD, Royal Children’s Hospital, Melbourne, Australia Cord blood stem cells certainly remain an active area of research, including for potential treatment of neurological diseases. I am not aware of any specific research using them for mito diseases nor of any developments that make it likely there will be a breakthrough that would be useful for mito disease any time soon. In general I think it is a great idea to donate cord blood but not so sure about the practicalities of cord blood storage in the USA, e.g. costs, intention to store for directed use versus donation, etc.

A: Sumit Parikh, MD, Cleveland Clinic I agree with Dr. Thorburn. While there are mitochondria in stem cells (including in cord blood cells) - we do not know how to utilize stem cells in general - and are not close to making use of them for mitochondrial disease (hopefully in 5 to 10 years).

(back to top)



Q: I have a two year old daughter with mitochondrial disease complex I.She is on the following drugs: Phenobarbital and Trileptal. She was still having break through seizures and was placed on Tennex last week to help calm her, I was told. Is this common? I was also told she was on the maximum dose and there was nothing else medication-wise. Are there other options? If not what does this mean for her life-wise? I have been told if they didn't get them under control she could 1) go into a coma and not come out  2) she could die 3) her organs would just stop working This is very scary; my husband and I have just been so upset. Could you please give us some insight on this matter? Is it normal for children with this diagnosis to respond this way? Also is there any truth to this information? We just need to know so we know what to expect. Thank You

A: I am sorry to hear about your daughter’s seizures. No, it doesn’t sound like you are at the limits of what could be done. Personally, I don’t like using Phenobarbital on someone who is 2 years old-too many side effects but that is my personal bias. The first question to answer is what does the EEG and her seizures look like? We use our seizure medications based on these two factors. For instance, if there are tonic spasms then clearly neither of the medications is proper as Phenobarbital nor Trileptal have efficacy in treating spasms. So, I would first find out what the EEG showed. Then talk to your epileptologist and find out how the seizures compare to the EEG. Based on that then formulate a plan of action. This can be time consuming as each child is different and respond to medications somewhat differently. I would start with a base medications, one may use what she is already on or change to another medication. Most will start with what they have the most experience with using. I usually start with Lamictal but that is just my choice. What we find is that when we have used two to three medications at their upper limit and seizures are not controlled, then likely we will not stop seizures completely using medications. Therefore, at this point we decide how many seizures are acceptable with respect to medication side effects. If the acyl carnitine profile is benign, then the ketogenic diet might be an option. We have had some good efficacy using this on children with electron transport chain defects. But, this is something you will have to talk over with your epileptologist. We have not found the VNS to be particularly effective in children with mitochondrial disease. For seizure lasting greater than 4 minutes; we usually use diastat (a benzodiazepine used rectally to abort seizures). I would highly recommend this medication as it may keep you out of the ED, which by now you have likely come to dislike.
The vast majority of patients with seizures never go into a coma. Even those with bad uncontrolled seizures do not. What we are trying to prevent is long seizures (10 minutes) that may produce neuronal damage. Thank goodness that greater than 85-90% of seizures are self limiting, lasting less than 2 minutes. No, her organs will not stop working. There are some side effects to our seizure medications that might reduce the performance of some of the organs, such as pancreatitis, low white blood count, low platelets, etc. But, these side effects are pretty well known and that is why we get labs to detect these side effects.
We find that having seizures in children with mitochondrial disease is common, especially with an electron transport chain defect. Seizures are often difficult to control. Working with an epileptologist is critical because each child is so different, that often there are many medication changes that occur.”

Answered by: Russell Saneto, DO, PhD

(back to top)



Q: Hello, My son has been diagnosed with mitochondrial myopathy with complex I and III defects. My question is that he seems to go through phases where he eats very little, has vomiting and when he does eat, his stomach becomes very bloated and hard. I was just curious if you had any recommendations on what to do when he goes through these spells. Thank you!

A: Episodes of vomiting in mitochondrial disease are not uncommon, and can have several different causes, which are briefly summarized here:
Cyclic vomiting - a migraine-like condition in which there are severe episodes of nausea, vomiting and lethargy (tiredness), with the absence of these symptoms between episodes. In a given patient, the episodes are similar to each other. Cyclic vomiting is treatable. For more information, visit www.cvsaonline.org
Gastrointestinal dysmotility refers to slow or abnormal movement of food, and can be at any level, from the top (GERD) to the bottom (constipation) of the GI tract. Unlike cyclic vomiting, the "episodes" are not as dramatic, and times of more and less symptoms tend to blur together. GERD (gastroesophageal reflux disease) is very common in mitochondrial disease. Delayed gastric emptying (DGE) is also common, and causes the early satiety (filling up fast) that you describe. Constipation, also common, can be so bad that food/feces builds up all the way to causing vomiting! Delayed gastric emptying and constipation can result in a hard bloated abdomen. Treatment depends on the level of the dysmotility and severity, but often consists of medications to make the gut move better (GERD, DGE), small frequent feeds (GERD, DGE) and polyethylene glycol (trade names: MiraLax, Glycolax, and others; constipation).
Many mito patients have more than one of the above conditions, sometimes all of them, at the same time. Finally, although much rarer, pancreatitis should be considered as well.

Answered by: Richard G. Boles, MD

(back to top)



Q: My daughter is 11 years old and has Complex I and IV mitochondrial disease. Her pediatrician was concerned with the curvature of her spine. We just completed an X-ray and found out she has a 24 degree curve. We will be visiting an orthopedic doctor soon. Should we consult our mitochonrial physician as well? What should we be aware of in regard to mitochondrial disease and scoliosis? What questions should we ask the orthopedic doctor as I am concerned they may not know as much about scoliosis and mitchondrial disease.

A: You are asking an excellent question. You do not mention whether your daughter has any neuromuscular problems. Neuromuscular problems (and especially if any hypotonia or hypertonia is assymetric) do lead to an increased risk of scoliosis. Since mitochondrial disorders can cause neuromuscular problems, there is therefore an increased risk of scoliosis in mitochondrial disease. I am not aware of any other reason that scoliosis would be increased in mitochondrial disease. Scoliosis is fairly common, and at age 11 your daughter may be in the growth spurt of puberty, and that is a common time for presentation of scoliosis - so the scoliosis may have nothing to do with the mitochondrial disorder. Regardless, it is a good idea to make certain that your mitochondrial physician is aware of what is going on. If your mitochondrial physician is also your neurologist, he or she can help to determine if there is an immediate neuromuscular cause or contribution of the scoliosis, and whether there might therefore be some specific treatment in addition to whatever the orthopedist has to recommend. And your mitochondrial physician can also help you to evaluate if any of the orthopedist's suggestions have any increased risk for an individual with mitochondrial disease. Most treatment for scoliosis is quite low risk, and I hope your daughter will never require any surgery, but if she does it will be your mitochondrial physician who will help the surgeons and anesthesiologists to know how best to help keep her safe.

Answered by: Carol Greene, MD

(back to top)



Q: My son was diagnosed with LHON. Now he has Lennox Gastaut syndrome. Can he safely go on a ketogenic diet?

A: I am sorry to hear that your son has Lennox-Gaustaut syndrome. In our center this epilepsy syndrome is extremely rare; in fact in 67 patients with electron transport disorders, we do not have a single patient with Lennox-Gaustaut. In the other 20 patients with either nuclear DNA mutations or mitochondrial DNA mutations (several with the LHON mutations), there is also no patient with Lennox-Gaustaut. However, this syndrome has been reported in children with mitochondrial disease in the literature. The reason a correct diagnosis is very important, is the treatment is based on having the epilepsy syndrome. So there should be mixed seizures: tonic, atypical absence and generalized tonic clonic.
Drop seizures are also extremely common. The ketogenic diet works best for the latter type of seizures as well as the atypical absence. The EEG should show slow spike and wave complexes, 1.5 - 2.5 Hertz as well as generalized paroxysmal fast. In children with electron transport chain disorders we usually begin the diet at a low ratio. This is because the ketone level often is high, out of proportion to the ratio (fats + protein/carbohydrate + protein). We have also found that side effects (mainly nausea and vomiting) are more pronounced in the electron transport chain children. Once we see that the child tolerates the diet well, we increase the ratio to efficacy and toleration. We monitor our kids on the diet very closely, for instance most all of them become selenium depleted and have to be supplemented.
So, your question of safety is generally yes it is safe. But, I always do an acyl carnitine profile before starting the diet just to make sure that fatty acids are being metabolized okay. If there is any problem with long chain fats, then the answer would be no. Depending on what other seizure medication is being used (usually not the ones used for Lennox-Gaustaut syndrome) there can be increased levels of triglycerides. We have found that the use of omega 3 can decrease triglycerides. Often removing the enzyme inducing seizure medication is the only way to reduce triglycerides. MCT oil supplementation does not seem to be tolerated well in our population. We have had fairly good luck with seizure control and the ketogenic diet in patients with electron transport chain defects.
In our regular Lennox-Gaustaut syndrome population (non-mitochondrial) the VNS stimulator works well. In one patient with a complex III disorder and drop seizures, we have found that the VNS stopped all his drop seizures, but unfortunately did not have any effect on his other seizures.

Answered by: Russell Saneto, DO, PhD

(back to top)



Q: If a person has MCAD, can she have kidney problems and migraines as a result of MCAD? The doctors have told her this is not possible. However, they also told her that it was impossible for her to have MCAD and Diabetes, and they were amazed when they found out that was her case. Could the MCAD be secondary to another mitochondrial abnormality, or be the primary cause of other mitochondrial dysfunction? Maybe she has more than one mitochondrial defect that is causing various unrelated issues? Any insight would help.

A: MCAD deficiency is easily diagnosable by a geneticist or metabolism specialist and shouldn't be confused with anything else. It does not cause kidney problems or migraine headaches. If a person has MCAD deficiency, they can still have a second disorder but it doesn't mean that MCAD caused it. For example, a person with MCAD deficiency can get the flu or a cold completely independent of the MCAD deficiency. Similarly, having MCAD deficiency doesn't preclude having mitochondrial disease but it would be rare and should be very well investigated before accepting it as true.

Answered by: Gerard Vockley, MD, PhD

(back to top)



Q: I'm going to have to have a root canal, fillings, etc. done at a dental office...no general anesthetic, only injections to gums with usual lidocane or some type of medication given to numb the area. Are there any meds I need to avoid at the dental office as a mito patient?

A: I am so sorry you have to get dental work (without anesthesia, at that). However, there are no direct contraindications to local anesthetics. Some individuals with mitochondrial disease have noted that the effects of even the local anesthetic last longer than expected. However this is typically a transient issue.
The key concern is typically with general anesthesia, prolonged fasting or 'major' surgery. In case your dental work requires any of this, please use the UMDF's outlined anesthesia precautions.

Answered by: Sumit Parikh, MD

(back to top)



Q: I'm a 42 yo female, married with two children. I've reviewed the Mito Doc posts and there is much discussion on GI problems. I was diagnosed with Leukodystrophy in 2002, and have recently (2006) been confirmed to have Mitochondrial COX defect in complex IV, with others in I, II, III as well (confirmed by muscle biopsy) . . . it has been devastating to me and my family. I have been empirically on a mito cocktail since early 2003, and found benefits for general ADL's. I take CoQ10, Carnitor, Alpha Lipoic Acid, B complex, Gamma E, Ocuvites, Vit C, probiotics and recently Miralax . . . which caused some dehydration problems. I suffer a whole slew of symptoms, mainly severe fatigue and loss of strength and many autonomic problems including temperature regulation, difficulty swallowing and GI dysmotility. I have recently had severe 'loss of motility' and subsequent constipation . . . my GI, PCP have helped greatly resolve initial problems. My question is: Is there a way to rehab the GI tract and increase the GI muscular tone and general motility? Or is this problem completely related to the Autonomic Nervous System with no over-ride?

A: I am so sorry to hear of how devastating this disease has been for you and your family. Through testing, it seems that you have several signs symptoms and also several complex deficiencies. I was wondering if you have had any additional testing done, including MNGIE (thymidine phosphorlyase) because of the leukodystrophy and mtDNA mutations/deletions/duplications and/or the polymerase gamma 1 mutation.  I would consult again with your PCP or GI doctor to see if any further additional tests could help you obtain a more specific diagnosis that is genetically based.
Dysmotility issues are very common in patients with mitochondrial disorders. The symptoms can range from mild (gastro-esophageal reflux, irritable bowel syndrome) to severe (chronic intestinal pseudo-obstruction).  When the problem is dysmotility, the symptoms can be fluctuating in nature.
Some patients do well on a modified diet alone, possibly with the use of supplements. I strongly suggest that anyone with GI symptoms work with a Nutritionist who is affiliated with a Metabolic Department or Gastroenterology Department of a University based hospital.; Any supplements need to be tried carefully and individually, as some of them can cause increased GI problems (such as Carnitine in particular but includes many others).
A specialist in the GI field of dysmotility is the best physician to help diagnose and manage symptoms. Other conditions may need to be ruled out; such as lactose intolerance, celiac disease, H. pylori infection, etc.  In general, reflux and irritable bowel may be treated medically when needed, and there are several medications that may help ease these symptoms. Many of the neuropathic pain medications we use in migraine or depression can be helpful in treating irritable bowel symptoms, including the SSRIs (Prozac, Celexa, Zoloft, Lexapro, etc.), tricyclics (Elavil, Pamelor, Doxepin), anti-seizure medications (Neurontin, Lyrica), and Periactin (an antihistamine).
When motility is the problem, there are specialized tests (manometry) that can be done only in special motility centers in order to properly diagnose pseudo-obstruction and determine if the problem is in the nerves or muscles of the GI tract. There are a limited number of medications that can be tried (erythromycin, octroetide), and some of them are better to use when we know which part of the GI tract is more affected. Finally, there have been surgical techniques used to help ease pressure and many GI physicians work closely with surgeons whose expertise is in GI procedures.

Answered by: Amy C. Goldstein, MD

(back to top)



Q: After going to the symposium we had some more questions. We understood that mitochondrial disease is passed down 100% maternally, but after the symposium we heard it can be from 1 to 100%. I (the mom) have it and all of my children plus my mom and her mom. Three out of four of my siblings got tested and all have it. When I spoke to some moms and they didn't have it I was a bit confused because I thought they would have it. Maybe you could explain how this works. Thank you.

A: It is not surprising you were confused as there are lots of different types of mitochondrial disease, and they are complicated even for those who have studied genetics. The term "mitochondrial disease" can be a little ambiguous and I assume you are referring to mitochondrial diseases caused by mutations in mitochondrial DNA, which are the type passed on maternally. Other mitochondrial diseases are caused by mutations (changes in the DNA sequence) in some of the 25,000 or so nuclear genes. With those genes we get one copy from mom and one from dad, except for the genes on the X and Y sex chromosomes. Mutations in nuclear genes can cause "mitochondrial disease" but are not associated with maternal inheritance. So if we focus on just the mitochondrial DNA, then you would have heard that our cells contain thousands of copies of mitochondrial DNA. In some mitochondrial diseases, for example most families with Leber's Hereditary Optic Neuropathy, every copy of the mitochondrial DNA contains the mutation that causes the disease. This is referred to as homoplasmy, and if the mother is homoplasmic then all her children will be homoplasmic, ie 100%. That doesn't mean they will all develop disease, since that may depend on other nuclear genes and the environment. In other mitochondrial DNA diseases, only some of the mitochondrial DNAs contain the mutation, while others are healthy. That situation is called heteroplasmy, and in that case different family members can have different amounts of mutant and healthy mitochondrial DNA. The more mutant DNA, the more likely the individual is to suffer symptoms of mitochondrial disease. With heteroplasmy, if the mother has a high proportion of mutant mitochondrial DNA, then the chances are that all or most of her children will have inherited some mutant mitochondrial DNA. Some may have 100% mutant, some may have 50% mutant and 50% healthy, while others may have 10% mutant and 90% healthy. The fact it can vary so much between different children is due to the "bottleneck effect" which results in big differences in the amount of mutant and healthy mitochondrial DNA being present in a woman's oocytes. In fact, it is possible that the bottleneck can mean that some oocytes only end up with healthy mitochondrial DNA so they have 0% mutant DNA. The lower the amount of mutant mitochondrial DNA that the mom has, the greater the chance that some of her oocytes will have 0% mutant mitochondrial DNA.
That explains why we inherit all our mitochondrial DNA from our mom, but if our mom has a heteroplasmic mitochondrial DNA mutation then the amount of mutant mitochondrial DNA that we inherit can be anywhere from 0% to 100%. I should also mention that the amount of mutant mitochondrial DNA is not always the same in every part of our body. So finding 0% mutant mitochondrial DNA in blood doesn't always mean that there is 0% present in muscle, brain, etc. That is one explanation for why some moms don't have the mutation, at least in blood. However, it is also possible that they not have it elsewhere in their body. The bottleneck effect occasionally results in new mutations appearing in women who don't have the mutation anywhere else in their body, but may have one or more oocytes containing a mitochondrial DNA mutation. If that oocyte is fertilized, then that can be how a child with a mitochondrial DNA mutation suddenly appears in a family with no history of mitochondrial disease.

Answered by: David R. Thorburn, PhD

(back to top)



Q: I have Mitochondrial Myopathy with Fiber 2. Could you please explain to me the difference between Fiber1, Fiber2. Thank you.

A: I am sorry to say that this diagnosis does not make much sense. "Mitochondrial myopathy" is due to a mitochondrial dysfunction (the biochemical and molecular causes can be many) that affects predominantly or exclusively the musculature. Fiber 2 probably refers to one of the two major fibers composing muscle: type 1 fibers are richer in mitochondria and type 2 fibers contain less mitochondria and rely more on glycogen metabolism. In this sense, it is somewhat paradoxical that a mitochondrial dysfunction should affect more type 2 fibers: usually, we see the opposite. More than this I cannot say.

Answered by: Salvatore DiMauro, MD

(back to top)



Q: I consider the most important testing I received was the respiratory enzyme. Is this possible without a muscle biopsy? I would like my relative to get it. If I have positive complex I deficiency, is it possible for this to be tested in my relatives?

A: Yes and no! In some patients the respiratory deficiency is only picked up in muscle, but in other patients can be detected in cultured skin fibroblasts. It would only be worth testing your relative if your complex deficiency is also detected in fibroblasts.

Answered by: Douglass M. Turnbull, MD, PhD

(back to top)



Q: I am 49 years of age and was diagnosed with MERRF as well as LHON. I started treatment for HEP C. To date, my liver enzymes are still rising instead of leveling out despite my viral load being undetectible. Before I went on treatment for HEP C virus, blood work showed elevated liver enzymes and since then they have been rising steadily. For this reason, I am told something else is causing the rise in liver enzymes other than my HEP C treatment and as such, my treating Physician is puzzled. My questions are as follows: In your opinion, could the rise in liver enzymes be caused by my Mitochondrial problems? Also, are there any other test that can be performed to ascertain the reason for the rise in liver enzymes and/or to rule out any other possible causes? What is the significance of RFLP in MERRF, and what are the clinical features associated with it? Had there ever been any studies done on Mito patients taking anti-viral drugs?

A: A chronic elevation in liver enzymes may be due to mitochondrial dysfunction (regardless of the mutation). I am glad the liver biopsy was okay. Did your physician evaluate you for other non-liver causes of elevated AST (muscle breakdown) and ALT levels (celiac disease)?
As to your second and third question, they may require quite a lengthy answer and more detailed review of the medical record. Visiting a clinical geneticist with an interest in mitochondrial medicine would be worthwhile.

Answered by: Sumit Parikh, MD

(back to top)



Q: About 12 years ago (before a confirmed Mito diagnosis) I began having episodes of severe diarrhea in which food would run through me undigested in about 6-8 hours. I was hospitalized for more than a week and the GI doc in town did an upper endoscopy and colonoscopy but all that was ever found was some inflammation that was not specific for any other disorders. For years the bouts of severe diarrhea would continue to occur periodically but because no one knew the cause, no one treated it. They are continuing with a greater intensity and now that I have been diagnosed with mito my GI doc gave me Levsin as needed. This has not been entirely effective but helpful at times. He has had to do more upper endoscopies for a few small ulcers. The ulcers are healed; however, they continue to see the gastritis and duodenitis. As far as the gastritis and duodenitis, is this connected to the mito?

A: Gastrointestinal dysmotility causing trouble swallowing, early satiety, diarrhea, or constipation is the most severe clinical feature of mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), but is also being recognized in other mitochondrial diseases such as MELAS. I presume that malabsorption has been excluded. It is important for your gastroenterologist to screen your gastrointestinal system for dysmotility, which could be causing your diarrhea and might be contributing to your gastritis and duodenitis. Other factors that could contribute to the slow healing of your gastritis include intestinal inflammation, bacterial overgrowth (which is not uncommon in the setting of intestinal dysmotility), and microscropic colitis. Hormonal factors are rare (e.g. gastrin or thyroid hormone abnormalities), but may be considered in this setting.

Answered by: Michio Hirano, MD

(back to top)


Showing 61 to 80 of 437      First | Prev | 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 | Next | Last

   [Go Back]



Ask the MitoDocSM Questions - The United Mitochondrial Disease Foundation - OLD