Domanda 299
I am 60 years
old and have recently been diagnosised with a Complex I
deficiency Mitochondrial disease. My foot doctor put me
on 250mg of Terbinafine tablets, (Lamsil), for toe nail
fungus. I have to take one pill a day for 3 months. I
was wondering if it was safe to take these pills since I
have this Mitochondrial disease.
Risposta di: Greg
Enns, MB, ChB
Terbinafine is an antifungal agent
commonly used to treat nail infections. Rare cases of
liver failure of unknown origin and decreased white
blood cell counts have been reported, but most adverse
reactions consist of common complaints or findings, such
as headache, gastrointestinal disturbance, rashes and
liver enzyme abnormalities (but not liver failure).
There is a single report in the medical literature of
terbinafine inducing mitochondrial dysfunction in a
leukemia cell line, but to my knowledge no reports of
using this medication in patients who have mitochondrial
disease. You should probably not take this medication
if you have significant liver disease, kidney disease,
immunodeficiency, or other serious disorder. In short,
it may be safe to use, but given the reactions described
above you should discuss the possibility of monitoring
your complete blood count and liver function (or any
other areas of concern depending on your medical history)
with your physician. In addition, your physician should
also consider the possible effects on any other
medications you are taking, because some drugs interact
with terbinafine.
Domanda 288
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?
Risposta di: Russell
Saneto, DO, PhD
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.
Domanda 287
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.
Risposta di: Sumit
Parikh, MD
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).
Domanda 286
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?
Risposta di:
Greg Enns, MB, ChB
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.
Domanda 285
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?
Risposta di: Russell
Saneto, DO, PhD
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.
Domanda 284
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)?
Risposta di: David
R. Thorburn, PhD
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.
Domanda 283
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?
Risposta di: Douglass
M. Turnbull, MD, PhD
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.
Domanda 282
Can a person with a mitochondrial
disease be an organ donor?
Risposta di: Sumit
Parikh, MD
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.
Domanda 281
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.
Risposte di:
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.
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).
Domanda 280
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
Risposta di: Russell
Saneto, DO, PhD
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.”
Domanda 279
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!
Risposta di: Richard
G. Boles, MD
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.
Domanda 278
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.
Risposta di: Carol
Greene, MD
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.
Domanda 277
My son was diagnosed with LHON. Now he
has Lennox Gastaut syndrome. Can he safely go on a
ketogenic diet?
Risposta di: Russell
Saneto, DO, PhD
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.
Domanda 276
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.
Risposta di:
Gerard Vockley, MD, PhD
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.
