Dr Korson's May Chat - Never Posted but Sent To Me after Editing

[Guest guest]

I was sent this about a month before the MDA Chat administrator retired. It was

not ever posted to the MDA site so I am sending it as I know many of you have

wanted to read this chat with Dr Korson.

Alice

Mon., May 17, 2004

Muscular Dystrophy Association (MDA) Chat

MITOCHONDRIAL (MITO) CHAT

Guest Host:

Mark Korson, M.D.

Dr. Korson's medical training at the University of Toronto was followed by a

pediatric residency at Toronto's Hospital for Sick Children. He completed a

genetics/metabolism fellowship at Children's Hospital in Boston. Dr. Korson was

Metabolism Service Director at Boston Children's for ten years until October

2000. He is currently the Associate Chief of the Metabolism Service at Tufts-New

England Medical Center and an Associate Professor of Pediatrics at Tufts

University School of Medicine. His interests include the natural history of

metabolic disease (treated and untreated) through childhood into adulthood, and

the development of teaching methods for training physicians, residents and

medical students and community professionals about metabolic/mitochondrial

disease.

Information contained in this chat transcript is not intended to replace, and

should not be interpreted or relied upon as, professional advice, whether

medical or otherwise. Please consult your own health care professional for

advice concerning the matter discussed herein.

=====================================================

MODERATOR -- Welcome Dr. Korson. It's great to have you here.

DR. KORSON -- It is a pleasure to participate in this chat room!

QUESTION -- I was just diagnosed with multi-complex defects of OXPHOS consistent

with a MELAS variant through muscle biopsy and other tests. The complexes and

which gene I don't know yet. My doctor is planning on discussing it next visit.

My plasma lactate level was 23 (NL 3-12) and though my pyruvate was high normal,

the ratio was 28. Is this all considered pretty high and what is considered

dangerous? I heard that lactic acidosis can be life threatening, how so?

DR. KORSON -- Elevated lactic acid levels are called " lactic acidemia " , or " high

lactic acid in the blood " . Lactic acid levels that are high enough to change the

pH of the blood and actually turn the blood acidic is referred to as " lactic

acidosis. " Lactic acidosis does not usually occur unless the the levels run

greater than three times the upper limit of normal, and occurs usually when

lactic acid levels climb quickly. Under those conditions, yes, the acidosis can

be dangerous. Many patients run mild elevations and show no clear symptoms as a

result. MELAS syndrome is associated with elevated levels only some of the time;

I have patients with the MELAS mutations who have NEVER had an elevated level.

That's a problem with the current inadequacies of our classification system.

QUESTION -- Are children with long chain fatty acids disorders (and on a normal

diet) in need of EFA supplementation and if given essential fatty acids will

they be able to properly metabolize them?

DR. KORSON -- If the child is following a " normal diet " (no fat restriction),

then extra essential fats (EFA) are not necessary. Patients with fatty acid

oxidation defects probably metabolize them slowly. However, under conditions of

fasting or illness, when metabolic needs are high, patients with defects cannot

metabolize them fast enough and run into trouble (develop symptoms).

QUESTION -- My daughter (17; Complex IV)has episodes of extreme irritability

that seem clearly out of the norm and can last a couple of hours. Normally, she

is very easy going. She is fasting intolerant, and the irritability sometimes

responds to food, but not always. These cluster for weeks, sometimes alternating

with days of extreme fatigue, drowsiness, and reduced muscle tone. Would you

please give possible reasons for irritability in MITO and possible treatments?

DR. KORSON -- There are numerous causes for irritability, including 1) - pain

(muscle cramps, nerve pain or neuropathy, headaches and migraine, abdominal

distress associated with poor motility), 2) - numbness/tingling (neuropathy), 3)

- seizures, 4) - dizziness (due to autonomic dysfunction), among others. Any of

these will run together with other symptoms. There are therapies for each, but

depend on making the current diagnosis of the cause. It may be worth giving a

trial of pain medication consistently for 1-2 days first to see if it is pain,

and if not consider one of the other causes.

QUESTION -- My infant son has a diagnosis of a partial defect of Complex I and a

suspected fatty acid oxidation disorder (elevated long chain fatty

acids/carnitine deficiency), all diagnosed through a frozen muscle biopsy. His

doctor (who evaluated the frozen biopsy, sent to him from Boston) has

recommended a fresh biopsy to investigate the results. What further information

could be gained from a fresh biopsy? Or more importantly, why can't the fresh

muscle biopsy wait? We are concerned as he has been through so much already

(G-tube placement complications, frozen muscle biopsy surgery, several

hospitalizations, etc).

DR. KORSON -- If the quality of the result is not in question (e.g., no concerns

about the technique or the processing of the specimen), then there seems to be a

real problem in your son's respiratory chain. Complex I defects are often

associated with fatty acid oxidation impairment, further supporting the

diagnosis. I am not sure that another biopsy is needed right now. The approach

to management will not change all that much, although further information may

help point toward slight changes in vitamin or cofactor therapies. Mitochondrial

DNA studies should probably be performed to evaluate a possible DNA mutation

that has been found to be associated with complex I defects, especially if there

is a family history suggestive of an energy problem.

QUESTION -- My 18-year-old son is on the autism spectrum, and has deteriorated

physically, developed movement disorders, and lost an awful lot of weight. He is

6 feet tall and only weighs 61 kg (lost 1 kg from a cold recently but regained

it). He was 67 kg nine months ago. He eats a lot and eats good food but won't

eat red meat.

My son's extreme fatigue, cramping from toes to hips when walking leisurely, and

inability to get up out of a chair gets worse as the day goes on and is very

scary at night resembling paralysis at times, yet he can still speak, but

appears breathless and complains of chest pains.

He had an appointment with a neurologist at our local hospital last week and was

told that he should see a psychiatrist because the neurologist didn't know what

was wrong and couldn't recommend any treatment or further testing.

Any ideas?

Would MCT oil help keep weight up? I give him CoQ10 300 mg/day in divided dose

and basically follow the MITO cocktail with the exclusion of carnitine, because

for some weird reason he looses even more weight when taking carnitine.

DR. KORSON -- A percentage of patients with " autism " have underlying metabolic/

mitochondrial disease. And a percentage of metabolic/mitochondrial patients have

autistic-like features. It is worth having your son evaluated by a metabolic

physician to consider underlying causes for his " autism " since the features you

describe are not typical for autism; mitochondrial disease should be considered.

Also remember that anyone who has a sleep disturbance (characterized by restless

sleeping, snoring, sluggishness when waking up on your own) can suggest sleep

apnea which is often associated with significant fatigue during the day; fatigue

can improve significantly when the sleep problem is addressed. And mitochondrial

patients are at risk for sleep apnea.

QUESTION -- I have a 100 percent TPN-dependant daughter who has a " clinical "

diagnosis of MITO who cannot receive CoQ10 (beacuse it has to be given through

the gut and in oil). I have heard that there is a company in Japan that will

possibly begin making a parenteral form of CoQ10 or that possibly it can be

given through the skin as a patch. Do you know about either of these products or

have more information?

DR. KORSON -- Yes, both of those products are in development. I know a

pharmacist who tried mixing coenzyme Q10 in a lipid-based gel patched to the

skin. The patient showed some clinical improvement for a brief while but blood

levels of coenzyme Q10 did not seem to show an increase compatible with the dose

he was taking, so I don't recommend trying this.

QUESTION -- My daughters carnitine level is normal but she has lots of autonomic

symptoms. Could extra carnitine help keep her blood pressures up? We've been

bolusing saline through her central line for diastolic less than 40.

DR. KORSON -- In general, the cardiologists seem to approach autonomic-based

blood pressure issues by 1)-providing more fluids on a regular basis (not just

in response to low pressures), 2)-providing fluids PLUS extra salt (to retain

fluid and regulate blood pressure), 3)-doing the above and treating with

medication (such as Florinef) which help retain fluid and stabilize blood

pressure). I don't believe carnitine helps but there is so much we don't know,

so to give extra carnitine a trial is reasonable. By the way, even patients with

" normal " carnitine levels can show a benefit from supplemental carnitine.

QUESTION -- I am 38 years old, with a clinical diagnosis of MITO. I have started

doing some walking for some exercise, but I am experiencing some bad leg cramps

on the front outside of my calf and burning throughout the whole leg, especially

down the back when walking. I have been walking for 6 weeks, two-three times a

week, for one to two miles each time. Things are not improving; they are getting

worse. I am trying to stay well hydrated and just started taking some magnesium

supplements to see if that helps. Do you have any further suggestions? I have a

fairly active job and am on my feet most of the day, but this is a completely

new symptom for me. I am trying to cut down the length of my walks, bought new

well-supportive shoes and am walking on a soft surface track. I am doing

everything I can think of.

DR. KORSON -- Listen to your body. If one-two miles bring on symptoms, try half

a mile then rest then another half-mile. The end point of your exercise should

be reached before you develop (significant) symptoms. If you are more fatigued

(i.e., " bad day " ), reduce your expectations. If it is hot or humid out, cut it

shorter or keep it indoors or work out in a cool-temp pool.

QUESTION -- My son is two years old and has LCHAD. He's been in the hospital for

so called " vomiting viral attacks " almost every month for about six months now.

I'm getting very concerned that something else may be wrong; it's not really

always viral. Two people recently mentioned CVS to me. I haven't had a chance to

look into it yet and wanted to know more about that or other areas to look into.

Also, he takes Carnitor and MCT, canola and cod liver oil, but I've been reading

up on CoQ10. Should he be on this and could it potentially help these acute

illnesses?

DR. KORSON -- How was the diagnosis made? If an enzyme or DNA mutation diagnosis

was not made, perhaps the LCHAD features are actually secondary to an underlying

mitochondrial problem (LCHAD patterns in biochemical testing occur in complex I

defects). By treating the mitochondrial disorder (including CoQ10), perhaps the

vomiting will come under better control. If the LCHAD deficiency is a proven

diagnosis, then try keeping him fed every 4-6 hours around the clock; this

should help prevent catabolism and its symptoms. If he responds, then gradually

increase the duration of overnight fasting to test his tolerance, remembering

that during illnesses or periods of poor intake, he must eat/drink every four

hours around the clock. By the way, make sure he doesn't have another cause of

vomiting which sets things off like migraine or reflux.

QUESTION -- I am 41 years old and diagnosed with mitochondrial myopathy and

encephalomyopathy. The muscle biopsy was not able to identify the particular

problem. My doctor says I have symptoms consistent with MITO and that I have

additional autoimmune problem. I have a big problem with exercise intolerance

that puts me in crisis (weakness with encephalopathy). However, I have not given

up on exercise and am trying a slow therapy program to build up my conditioning.

I have an obesity problem and cannot seem to keep from gaining weight without

activity. What are your thoughts on the value of an exercise program? And, do

you think strengthening should be part of it? Please take into consideration

that without exercise my weight and cholesterol go up.

DR. KORSON -- Exercise is important to maintain muscle tone, coordination, range

of motion and prevent atrophy. As I mentioned before, you need to listen to your

body and test its limits. Keep active with regular breaks and resting, modifying

your exercise according to your daily status. On low energy days, poor sleep

days, hot/humid days, cut back on your workout. On better days, increase it. The

end point of your workout should not be pain or profound exhaustion. If you

continue to gain weight, check for thyroid problems (a risk in mitochondrial

disease) and/or cut further on calories -- you might want to consult a dietitian

to help in this regard.

QUESTION -- I've heard that glycine is therapeutic for GA2? How does it work and

what does it do? My son is seven years old.

DR. KORSON -- Glycine (an amino acid) and carnitine (a body cofactor) bind to

various chemicals in the body. Carnitine binds with greater affinity (tighter

bond) to some chemicals, glycine to others. Carnitine is generally the cofactor

of choice for GAII; it binds some of the accumulating chemicals (like glutaric

acid) and helps facilitate their excretion from the body. These chemicals in

larger quantities often tie up an important body cofactor called Coenzyme A; by

binding the chemical directly, the carnitine frees up the coenzyme A to do all

it needs to do. Glycine does the same with certain chemicals, but I would have

to research what benefits have been shown for glycine in GAII.

QUESTION -- My pulmonary function test indicated an early anaerobic metabolism

and profoundly reduced carnitine levels and there was an indication in my labs

which suggested the possibility of a mild MADD, GAII disorder (actylcarnitine

elevations). Can the early anaerobic metabolism be caused by a MADD disorder

alone - or is it more likely that a mitochondrial disorder is behind that

problem?

DR. KORSON -- MADD (multiple acyl CoA dehydrogenase deficiency) is also know as

GAII (glutaric acidemia type II). MADD is a form of energy disorder affecting

the function of the mitochondrion (it interferes with many reactions including

one that involves delivering high energy electrons from the Krebs cycle where

they are formed to the electron transport chain where they are used). So it

could very well be the cause of your lab results.

QUESTION -- My 18 year old son has mtDNA mitochondrial Disease, severe

Dysautonomia, severe Cyclic Vomiting. He also has exercise and heat intolerance.

He receives monthly hydration for three days. The hydration really seems to perk

him up. Why does he do so much better after the hydration?

DR. KORSON -- Several possible reasons. 1)-Autonomic dysfunction is often

associated with blood pressure problems and fluids help. 2)-If there is sugar in

the IV, the extra calories might help as well especially if he is not a good

eater or has problems with his gut function. 3)-If this is migraine related,

since underhydration and/or undernutrition can precipitate migraine (and

vomiting), fluids can help. 4)-Whatever cyclic vomiting is, it seems to respond

to fluids. Have you tried any of these on a regular basis as prevention: Regular

fluids daily through a PICC line or central IV (autonomic), high-dose riboflavin

daily (migraine), Periactin daily (migraine, cyclic vomiting).

QUESTION -- What sort of pre-conception or perhaps pre-natal technology is

available to couples who have a child diagnosed with mitochondrial disease and

wish to have another child? Is there any technology that can reduce or even

eliminate the risk for future children? I have heard of pre-genetic implantation

diagnosis (PGD), but did not know if mitochondrial disease can be identified

through this procedure. We have one child with mito. and another who is

unaffected. Our affected child's disorder has been identified as a nuclear

mitochondrial disorder.

DR. KORSON -- If a DNA mutation has been identified as part of the diagnosis

(very rare due to limits in our technology), then prenatal diagnosis or PGD are

options. If only a respiratory chain enzyme diagnosis was made (vast majority of

cases to date), many labs do not feel comfortable with the accuracy of the

prenatal enzyme testing to make a prenatal diagnosis. That leaves looking for

possible evidence from other forms of testing like ultrasound (e.g., if a small

head -- microcephaly -- is part of the presentation).

QUESTION -- I just had a biopsy that said I had a profound deficiency of

succinate cytochrome C reductase. I believe this is complex II/III. How does

this present itself as far as symptoms and transmission? I also have three

affected kids.

DR. KORSON -- There are a variety of clinical presentations that are possible

with disorders caused by problems in complexes II or III. The majority of

defects involving complex III and all involving complex II (depending on where

the primary defect is) are autosomal recessive reflecting genetic abnormalities

in the nucleus. A minority of complex III defects are caused by genetic

abnormalities in mitochondrial DNA which is maternally inherited.

QUESTION -- Our son is now 7, was diagnosed in infancy with a rare terminal

seizure disorder, muscle biopsy came out -- no MITO disorder. One year ago, his

breathing became erratic, to a point that he can have apnea every 30-60 sec. for

30 sec to three min. He does not realize this and it happens continuously when

he's awake and asleep with beautiful rhythmic breathing. He is now on 4-6 liters

of oxygen through nasal prongs, 24 hours a day. For some unknown reason, this

keeps him gong; without it, he is totally blue centrally within about a minute

or two. His doctors decided that he is in brainstem failure due to a MITO

disorder. How can this be since originally his test came back -- no MITO

disorder? His quality of life is still good, though he gets tired. Less than a

year ago, he was given two weeks to live, but he is our fighter. Any patients

similar and what can we expect?

DR. KORSON -- Central apnea (brain failure to stimulate breathing) and

peripheral apnea (due to obstruction and/or muscle weakness) can occur in

mitochondrial disease. But there are other causes for apnea that are not

mitochondrial in origin. If your son does not have a mitochondrial cause,

there's your answer. If he does, then you should know that muscle biopsy results

provide only one piece of information that helps determine a diagnosis. I have

other patients who have confirmed DNA abnormalities that prove a mitochondrial

diagnosis but the muscle biopsy results were " normal. " The testing that

currently exists for making a diagnosis is OK but not the most sensitive nor

specific; we need to develop better testing.

MODERATOR -- Thank you Dr. Korson for your time tonight and his wonderful

answers.

=====================================================

Previous MDA Mitochondrial Experts Chat transcripts are available on the

Upcoming Mitochondrial Chats and Transcripts page.

Please check the MDAchat Calendar for the complete chat schedule.

Thanks for joining us and we hope to " see " you back!

[Guest guest]

Alice, Tks so much for posting this. Very interesting. I have always

wanted to read some of the chat transcripts and will try to get that

done now that I can be online more.

Barbara

>

> I was sent this about a month before the MDA Chat administrator

retired. It was not ever posted to the MDA site so I am sending it

as I know many of you have wanted to read this chat with Dr Korson.

>

> Alice

>

>

>

>

>