Re: how do you get the ER dr to listen?/long

[Guest guest]

Here is the article written by Cohen and Saneto on how to treat a

child with mito. I have found (and it works most of the time) that

if you act like the most knowledgable mom, request what you want

done and have all of your facts with you, they tend to question you

less. They don't want to screw up. _Scare them!!!!!

Copy and paste this. Or you can find it at www.umdf.org

Good luck, Dawn

Management Strategy for Acute Illness in Patients with Mitochondrial

Cytopathy

by P. Saneto, DO, PhD, Pediatric Epilepsy

and Bruce H. Cohen, MD, Pediatric Neurology

The Cleveland Clinic Foundation, Cleveland, OH.

Introduction

The precarious health of a patient with a mitochondrial cytopathy

represents the fine line between little energy reserve and potential

energy deficiency. When demands of added energy requirements occur,

as they do in an acute illness, the decreased reservoir of stored

energy in a patient with a mitochondrial

cytopathy often cannot compensate for the new energy demand. When

combined with the decreased inherit capacity to manufacture energy,

the patient's bioenergetic health is altered and a bioenergetic

crisis can occur. This is especially true in young children, who

have little energy reserves to begin with, and in those with a

severe mitochondrial cytopathy. Although the number of things that

can cause excessive bioenergetic stress is large, we mostly see

compromised bioenergetic health in the context of another illness.

Viral illnesses and fevers for example, can have mitochondrial

consequences.

A quick and simple review of mitochondrial function is important to

understand this article. We consume

food to make the energy our body needs to function. The energy in

food is contained in the cleavable bonds

between the atoms in molecules of sugars (carbohydrate), fats, and

proteins. Healthy mitochondria will generate 36 molecules of ATP

(adenine triphosphate, each ATP represents a unit of energy) for

each molecule of glucose that the mitochondria can burn or oxidize.

If the mitochondria do not function (which is not compatible with

even a brief life of any person), glucose is not fully burned and

only 2 ATP molecules will be produced. In this situation, there is

also the production of two molecules of lactic acid. Studies of

mitochondrial function in some of our sicker patients show that

under ideal laboratory conditions, only about 40 - 60% of the

maximal energy can be produced (14 - 21 ATP molecules for each

glucose burned). This is an estimate of theoretical ATP production,

which would decrease if laboratory conditions mimicked what occurs

in the body during severe viral illnesses, dehydration, and high

fever.

A useful analogy is to think of an eight-cylinder car that is

running on only 6 or 7 cylinders. As long as the car is on

horizontal ground the car's performance can appear acceptable.

However, when the demands are increased, such as when the car is

loaded with passengers, attempts to climb a hill, or accelerates to

enter the freeway, there is not sufficient energy performance to

accomplish the task. The car knocks, sputters, and lags in

acceleration. Under these circumstances, the car can stop working

completely. In everyday life, the patient with a mitochondrial

cytopathy may function well enough to get by. But when the demands

of an illness or other stressful situation require a higher

performance state, the ability of the body to manufacture the needed

energy to meet that demand is not optimal. It takes longer for a

mitochondrial patient to recover from an illness, and sometimes the

illness is far more severe than if the same illness happened to

someone with normal mitochondrial function. So when illness occurs,

the mitochondrial cytopathy patient is faced with a situation of

having both less energy reserves to fight off the illness and the

inability to maximize energy production, to help overcome and

recover from the illness' effects on the body.

Little is known how to prevent an energy imbalance and possible

subsequent physiological damage. There is not much in the medical

literature that is instructive in medically managing the crises of

illness or other

stressful event in a mitochondrial patient. What follows is based on

our experience and understanding of some of the practical and

theoretical implications of how the body's biochemistry affects the

bioenergetic health of a mitochondrial patient.

Preparation is the Key to Energetic Health

There is a wide spectrum of mitochondrial cytopathies. Each one is

expressed in a unique way that is particular to a specific person.

Therefore, there is no " one " best treatment for those with a

mitochondrial cytopathy. Each patient has to be cared for on an

individual basis. Furthermore, our current understanding of

mitochondrial diseases is limited and hence, a best treatment

protocol does not exist. At present, there are many more unknowns

than proven treatments in the medical care of a patient with a

mitochondrial cytopathy.

The fragility of someone with a mitochondrial cytopathy requires a

working knowledge of what signs to look for during an acute illness.

For the purposes of this discussion, we will be discussing the

management of fevers, inability to consume enough liquid and food,

and dehydration. Some patients vomit excessively, others have

increased tremulousness, while still others stop drinking and

eating, and some have cognitive changes. It is important for the

parent or caregiver to know these signs (Table 1) for their loved

one and call their doctor if these signs develop. In addition, there

should be a good working relationship with the primary care

physician, so when the parent or caregiver begins to see the signs

of rapid bioenergetic decline, the physician can make arrangements

for hospitalization. A plan for such events should be well developed

by the physician prior to a crisis. Past experiences will dictate

the need for hospitalization and the immediate treatment once the

patient has arrived at the hospital. Unnecessary hospitalization may

occur on occasion, when the patient is not as sick as originally

believed to be, but both physician and caregivers quickly learn when

and when not hospitalization is needed.

Table 1. Some Worrisome Signs

Unexplained or excessive feverAlteration of usual level cognitive

functionConfusion, excessive sleepiness, excessive

cryingVomitingLoss of appetiteRapid breathingAbdominal pain

At the first signs of an illness, the parent or caregiver should be

quick to implement treatment. This generally includes fluid and

sugar, and we find that some common sports drinks such as Gatorade

help. High carbohydrate meals, given by frequent feedings, also may

help replenish and sustain the needed levels of glucose for

metabolism. For example, we have used added uncooked cornstarch in a

meal to increase the level of glucose in the meal.

The use of medication to reduce fever, such as ibuprofen or

acetaminophen should be used. The doctor should calculate the proper

dose of these medications (10 – 15 mg/kg/dose given every 4 – 6

hours), so that there are no fevers.

Treatment for Worsening Clinical Status

It is difficult to pinpoint the time when the patient needs

hospitalization. Experience and communication with the

physician/heath care team are needed. Decisions can be made when the

parent/caregiver notices that, despite the added measures of

increased fluids and extra carbohydrate-containing meals/drinks, the

patient has not responded appropriately. This would be more urgent

if the patient continues to worsen. For each patient, the dictating

symptoms are different, however, through consultation with the

health care team the appropriate decision can be made.

Once the decision is made, the patient and parent/caregiver should

go to the nearest hospital. We tend to have our patients admitted

directly to the hospital, but this will vary according to the

patient's doctor. Our decisions on what to do next are based on our

knowledge of what deficit our patient may have. Once the patient has

been checked into the hospital, we have a general plan for

proceeding ahead. Most patients will

need blood and urine tests, placement of an IV, and fluids

initiated.

Laboratory Tests: The underlying reason for the change in

bioenergetic status needs to be addressed. For example, if there is

an infection, this may need to be treated. If it is asthma, then the

proper respiratory medications need to be given.

Laboratory tests may need to be obtained, including lactate,

pyruvate, ammonia, electrolytes and urine analysis. These values may

assist in understanding the depth of bioenergetic compromise. For

instance, if the lactate level is high, then the amount of dextrose

added to the balanced salt solution used for hydration can be

determined. The level of BUN will help determine the level of

dehydration and the rate of fluid administration. If the urine

analysis indicates that ketone bodies are being excreted in the

urine, this is an indication that fats are being mobilized and maybe

carnitine needs to be added to the fluids.

Dehydration: The degree of dehydration is very important. This is

because dehydration may adversely affect the brain, muscle, heart,

and kidney. Even mild degrees of dehydration, caused by vomiting,

diarrhea, or fever may greatly limit the kidney's ability to get rid

of a toxic metabolite, set the conditions for rising metabolite

levels and induce further injury. This is the likely mechanism for

the evolution of basal ganglia injury in cases of methyl-malonic

aciduria and type I glutaric aciduria.

We usually begin dextrose containing a balanced salt solution,

usually D5 or D10 with 1/4 or 1/2 nor-mal saline (a salt mixture

containing 5% or 10% dextrose) and added carnitine. Given a

particular situation, the amount of salt or sugar could be higher or

lower in the IV solution. The percentage of dextrose containing

fluid depends on the abnormality of the patient. The rate at which

fluid is given is individualized depending on the degree of

dehydration, and is the same regardless of whether or not someone

has a mitochondrial disease. The normal criteria used to decide

whether to administer IV fluids should be abandoned in those with

acute illness and dehydration, as oral rehydration therapy does not

offer the same degree of control and there is not as much room for

error in someone with a mitochondrial disease.

Glucose: Why use added dextrose (glucose) in a mitochondrial

cytopathy patient that is dehydrated and/or has lactic acidosis?

Let's use the automobile engine analogy again. In a mitochondrial

cytopathy patient, the need for fuel is more pronounced, than in a

normal patient. Since the engine does not function optimally, we

need to either increase the octane of the fuel so the engine gets

more output from the fuel or give the engine more fuel to burn. By

giving the patient more glucose in intravenous fluids we are

accomplishing both, more glucose or fuel to burn and a higher octane

by enhancing the purity of the fuel to burn, and there-fore produce

more immediate energy (instead of the fatty acids from the breakdown

of fats). By treating dehydration, we are also producing an

environment for the engine, which is better for energy efficiency.

In more scientific terms, what we are trying to do is decrease the

lactic acidosis while expanding the volume of fluid in the body.

Lactate, but also other toxins, can be poisons to the brain and as

previously mentioned dehydration can concentrate toxic metabolites

and decrease the kidney's ability to get rid of these metabolites.

Lactate is the by-product of inefficient glucose metabolism due to

mitochondrial dysfunction. When lactate builds up, it causes the

blood to become acidotic. The liver, in a non-mitochondrial patient,

can utilize much of the lactate produced to remake glucose for

storage and also burn it for fuel. However, when the pH falls below

a certain point, below 7.1, the liver ceases using lactate and

instead produces lactate. By giving fluid, we are expanding the

volume of the blood and allowing the kidneys to help remove some of

the toxins. In addition, the added fluid is helping the kidneys

reverse the acidosis. Under conditions of severe illness, it is

easier for the body to burn glucose, rather than fat, for energy.

The hopeful result of IV flu-ids with added glucose and carnitine is

the resolution of lactic acidosis, correction of electrolyte

balance, and the resolution of symptoms. It is critical to note that

excess of glucose can be highly toxic to a person with pyruvate

dehydrogenase (PDH) deficiency. In some situations of severe

mitochondrial failure, excess glucose can result in worsening lactic

acidosis as well.

In certain emergent cases, we have had to add an insulin drip (0.03

units/kg/hr - 0.1 units/kg/hr) to help improve mitochondrial

function by making glucose more available to the mitochondria and

lowering free

fatty acid levels, which can improve the function of sick

mitochondria. These are very select cases, and consultation with a

mitochondria expert is needed to assess and implement insulin in

these special cases.

Levo-Carnitine: In some patients, we will give a bolus of levo-

carnitine (usually 50 mg/kg, followed by 100 mg/kg/day in 3 divided

doses) as these patients usually present with a lactate acidosis and

have begun to break down fats into fatty acids. In the analogy of

the car engine, when the fuel is improper for the engine there are

by-products produced that can decrease the performance of the

engine. One can think of carnitine as a fuel additive to help

prevent the build up of toxic by-products created by inefficient

fuel utilization.

Carnitine binds toxic-free fatty acids and organic acids. In

addition, it acts as a mitochondrial membrane stabilizer (seals

the " leaky " gasket). Often patients with mitochondrial cytopathies

have a secondary carnitine deficiency as a result of overproduction

of free fatty acids. The carnitine deficiency would be worsened by

an acute insult to the mitochondria and the metabolic machinery.

Added carnitine during the acute stage of an illness would help in

removing toxins and improving the carnitine deficiency. However,

there are situations when added carnitine may not be needed or may

potentially worsen the situation

Other Supplements: There are occasions when other supplements, in

addition to those above, may be needed. We have patients who have

severe muscle and peripheral nerve impairment when illness also

induces changes in bioenergetic homeostasis, very similar to chronic

inflammatory demyelinating

polyneuropathy. Other patients have severe movement disorders, such

as dystonia. We have found that intravenous gamma globulin (1 - 2

gm/kg in 1 or 2 doses) temporarily improves these conditions.

Although not FDA approved for these diseases, we have seen this

treatment help reverse neuropathic weakness and dystonic movements.

There is some experience with the use of creatine in patients having

mitochondrial myopathies. We have used creatine as only a short-term

treatment when trying to prevent a patient from being placed on a

breathing machine. The body adapts to long term use of creatine and

presumably its effectiveness lessens. We would only recommend these

types of treatment in consultation

with a mitochondria expert.

Conclusion

There are a few important points to remember when dealing with an

intervening illness in a person with a

mitochondrial cytopathy.

1. The patient or caregiver, along with the primary care

physician, should develop a plan of how these illnesses will be

approached ahead of time.

2. In many patients, there is little ability to compensate during

an acute illness, so early intervention and the use of IV fluids are

often warranted.

3. Once IV hydration has started, it may be necessary to stop all

attempts at feeding, allowing the bowel to rest, until the patient

begins to request fluids or food.

4. Improvement can be slower than would be expected in otherwise

healthy persons, but most patients restart oral hydration and

feeding within 12 - 24 hours of the IV fluids having begun.

5. The source of infection should be sought, and if there is a

bacterial infection, it should be treated with appropriate

antibiotics. Viral infections should not be treated with

antibiotics, as these do not work against viruses and many

antibiotics can further limit mitochondrial function.

Glossary of Terms

Sugars: a general term used to define a simple carbohydrate.

Glucose: a common sugar contained in sucrose (table sugar) or

lactose (milk sugar).

Dextrose is the pharmaceutical term for glucose.

Bioenergetic Health: a descriptive term used to define the ability

to produce an adequate supply of energy that will meet the body's

energy demands.

[Guest guest]

Here is the article written by Cohen and Saneto on how to treat a

child with mito. I have found (and it works most of the time) that

if you act like the most knowledgable mom, request what you want

done and have all of your facts with you, they tend to question you

less. They don't want to screw up. _Scare them!!!!!

Copy and paste this. Or you can find it at www.umdf.org

Good luck, Dawn

Management Strategy for Acute Illness in Patients with Mitochondrial

Cytopathy

by P. Saneto, DO, PhD, Pediatric Epilepsy

and Bruce H. Cohen, MD, Pediatric Neurology

The Cleveland Clinic Foundation, Cleveland, OH.

Introduction

The precarious health of a patient with a mitochondrial cytopathy

represents the fine line between little energy reserve and potential

energy deficiency. When demands of added energy requirements occur,

as they do in an acute illness, the decreased reservoir of stored

energy in a patient with a mitochondrial

cytopathy often cannot compensate for the new energy demand. When

combined with the decreased inherit capacity to manufacture energy,

the patient's bioenergetic health is altered and a bioenergetic

crisis can occur. This is especially true in young children, who

have little energy reserves to begin with, and in those with a

severe mitochondrial cytopathy. Although the number of things that

can cause excessive bioenergetic stress is large, we mostly see

compromised bioenergetic health in the context of another illness.

Viral illnesses and fevers for example, can have mitochondrial

consequences.

A quick and simple review of mitochondrial function is important to

understand this article. We consume

food to make the energy our body needs to function. The energy in

food is contained in the cleavable bonds

between the atoms in molecules of sugars (carbohydrate), fats, and

proteins. Healthy mitochondria will generate 36 molecules of ATP

(adenine triphosphate, each ATP represents a unit of energy) for

each molecule of glucose that the mitochondria can burn or oxidize.

If the mitochondria do not function (which is not compatible with

even a brief life of any person), glucose is not fully burned and

only 2 ATP molecules will be produced. In this situation, there is

also the production of two molecules of lactic acid. Studies of

mitochondrial function in some of our sicker patients show that

under ideal laboratory conditions, only about 40 - 60% of the

maximal energy can be produced (14 - 21 ATP molecules for each

glucose burned). This is an estimate of theoretical ATP production,

which would decrease if laboratory conditions mimicked what occurs

in the body during severe viral illnesses, dehydration, and high

fever.

A useful analogy is to think of an eight-cylinder car that is

running on only 6 or 7 cylinders. As long as the car is on

horizontal ground the car's performance can appear acceptable.

However, when the demands are increased, such as when the car is

loaded with passengers, attempts to climb a hill, or accelerates to

enter the freeway, there is not sufficient energy performance to

accomplish the task. The car knocks, sputters, and lags in

acceleration. Under these circumstances, the car can stop working

completely. In everyday life, the patient with a mitochondrial

cytopathy may function well enough to get by. But when the demands

of an illness or other stressful situation require a higher

performance state, the ability of the body to manufacture the needed

energy to meet that demand is not optimal. It takes longer for a

mitochondrial patient to recover from an illness, and sometimes the

illness is far more severe than if the same illness happened to

someone with normal mitochondrial function. So when illness occurs,

the mitochondrial cytopathy patient is faced with a situation of

having both less energy reserves to fight off the illness and the

inability to maximize energy production, to help overcome and

recover from the illness' effects on the body.

Little is known how to prevent an energy imbalance and possible

subsequent physiological damage. There is not much in the medical

literature that is instructive in medically managing the crises of

illness or other

stressful event in a mitochondrial patient. What follows is based on

our experience and understanding of some of the practical and

theoretical implications of how the body's biochemistry affects the

bioenergetic health of a mitochondrial patient.

Preparation is the Key to Energetic Health

There is a wide spectrum of mitochondrial cytopathies. Each one is

expressed in a unique way that is particular to a specific person.

Therefore, there is no " one " best treatment for those with a

mitochondrial cytopathy. Each patient has to be cared for on an

individual basis. Furthermore, our current understanding of

mitochondrial diseases is limited and hence, a best treatment

protocol does not exist. At present, there are many more unknowns

than proven treatments in the medical care of a patient with a

mitochondrial cytopathy.

The fragility of someone with a mitochondrial cytopathy requires a

working knowledge of what signs to look for during an acute illness.

For the purposes of this discussion, we will be discussing the

management of fevers, inability to consume enough liquid and food,

and dehydration. Some patients vomit excessively, others have

increased tremulousness, while still others stop drinking and

eating, and some have cognitive changes. It is important for the

parent or caregiver to know these signs (Table 1) for their loved

one and call their doctor if these signs develop. In addition, there

should be a good working relationship with the primary care

physician, so when the parent or caregiver begins to see the signs

of rapid bioenergetic decline, the physician can make arrangements

for hospitalization. A plan for such events should be well developed

by the physician prior to a crisis. Past experiences will dictate

the need for hospitalization and the immediate treatment once the

patient has arrived at the hospital. Unnecessary hospitalization may

occur on occasion, when the patient is not as sick as originally

believed to be, but both physician and caregivers quickly learn when

and when not hospitalization is needed.

Table 1. Some Worrisome Signs

Unexplained or excessive feverAlteration of usual level cognitive

functionConfusion, excessive sleepiness, excessive

cryingVomitingLoss of appetiteRapid breathingAbdominal pain

At the first signs of an illness, the parent or caregiver should be

quick to implement treatment. This generally includes fluid and

sugar, and we find that some common sports drinks such as Gatorade

help. High carbohydrate meals, given by frequent feedings, also may

help replenish and sustain the needed levels of glucose for

metabolism. For example, we have used added uncooked cornstarch in a

meal to increase the level of glucose in the meal.

The use of medication to reduce fever, such as ibuprofen or

acetaminophen should be used. The doctor should calculate the proper

dose of these medications (10 – 15 mg/kg/dose given every 4 – 6

hours), so that there are no fevers.

Treatment for Worsening Clinical Status

It is difficult to pinpoint the time when the patient needs

hospitalization. Experience and communication with the

physician/heath care team are needed. Decisions can be made when the

parent/caregiver notices that, despite the added measures of

increased fluids and extra carbohydrate-containing meals/drinks, the

patient has not responded appropriately. This would be more urgent

if the patient continues to worsen. For each patient, the dictating

symptoms are different, however, through consultation with the

health care team the appropriate decision can be made.

Once the decision is made, the patient and parent/caregiver should

go to the nearest hospital. We tend to have our patients admitted

directly to the hospital, but this will vary according to the

patient's doctor. Our decisions on what to do next are based on our

knowledge of what deficit our patient may have. Once the patient has

been checked into the hospital, we have a general plan for

proceeding ahead. Most patients will

need blood and urine tests, placement of an IV, and fluids

initiated.

Laboratory Tests: The underlying reason for the change in

bioenergetic status needs to be addressed. For example, if there is

an infection, this may need to be treated. If it is asthma, then the

proper respiratory medications need to be given.

Laboratory tests may need to be obtained, including lactate,

pyruvate, ammonia, electrolytes and urine analysis. These values may

assist in understanding the depth of bioenergetic compromise. For

instance, if the lactate level is high, then the amount of dextrose

added to the balanced salt solution used for hydration can be

determined. The level of BUN will help determine the level of

dehydration and the rate of fluid administration. If the urine

analysis indicates that ketone bodies are being excreted in the

urine, this is an indication that fats are being mobilized and maybe

carnitine needs to be added to the fluids.

Dehydration: The degree of dehydration is very important. This is

because dehydration may adversely affect the brain, muscle, heart,

and kidney. Even mild degrees of dehydration, caused by vomiting,

diarrhea, or fever may greatly limit the kidney's ability to get rid

of a toxic metabolite, set the conditions for rising metabolite

levels and induce further injury. This is the likely mechanism for

the evolution of basal ganglia injury in cases of methyl-malonic

aciduria and type I glutaric aciduria.

We usually begin dextrose containing a balanced salt solution,

usually D5 or D10 with 1/4 or 1/2 nor-mal saline (a salt mixture

containing 5% or 10% dextrose) and added carnitine. Given a

particular situation, the amount of salt or sugar could be higher or

lower in the IV solution. The percentage of dextrose containing

fluid depends on the abnormality of the patient. The rate at which

fluid is given is individualized depending on the degree of

dehydration, and is the same regardless of whether or not someone

has a mitochondrial disease. The normal criteria used to decide

whether to administer IV fluids should be abandoned in those with

acute illness and dehydration, as oral rehydration therapy does not

offer the same degree of control and there is not as much room for

error in someone with a mitochondrial disease.

Glucose: Why use added dextrose (glucose) in a mitochondrial

cytopathy patient that is dehydrated and/or has lactic acidosis?

Let's use the automobile engine analogy again. In a mitochondrial

cytopathy patient, the need for fuel is more pronounced, than in a

normal patient. Since the engine does not function optimally, we

need to either increase the octane of the fuel so the engine gets

more output from the fuel or give the engine more fuel to burn. By

giving the patient more glucose in intravenous fluids we are

accomplishing both, more glucose or fuel to burn and a higher octane

by enhancing the purity of the fuel to burn, and there-fore produce

more immediate energy (instead of the fatty acids from the breakdown

of fats). By treating dehydration, we are also producing an

environment for the engine, which is better for energy efficiency.

In more scientific terms, what we are trying to do is decrease the

lactic acidosis while expanding the volume of fluid in the body.

Lactate, but also other toxins, can be poisons to the brain and as

previously mentioned dehydration can concentrate toxic metabolites

and decrease the kidney's ability to get rid of these metabolites.

Lactate is the by-product of inefficient glucose metabolism due to

mitochondrial dysfunction. When lactate builds up, it causes the

blood to become acidotic. The liver, in a non-mitochondrial patient,

can utilize much of the lactate produced to remake glucose for

storage and also burn it for fuel. However, when the pH falls below

a certain point, below 7.1, the liver ceases using lactate and

instead produces lactate. By giving fluid, we are expanding the

volume of the blood and allowing the kidneys to help remove some of

the toxins. In addition, the added fluid is helping the kidneys

reverse the acidosis. Under conditions of severe illness, it is

easier for the body to burn glucose, rather than fat, for energy.

The hopeful result of IV flu-ids with added glucose and carnitine is

the resolution of lactic acidosis, correction of electrolyte

balance, and the resolution of symptoms. It is critical to note that

excess of glucose can be highly toxic to a person with pyruvate

dehydrogenase (PDH) deficiency. In some situations of severe

mitochondrial failure, excess glucose can result in worsening lactic

acidosis as well.

In certain emergent cases, we have had to add an insulin drip (0.03

units/kg/hr - 0.1 units/kg/hr) to help improve mitochondrial

function by making glucose more available to the mitochondria and

lowering free

fatty acid levels, which can improve the function of sick

mitochondria. These are very select cases, and consultation with a

mitochondria expert is needed to assess and implement insulin in

these special cases.

Levo-Carnitine: In some patients, we will give a bolus of levo-

carnitine (usually 50 mg/kg, followed by 100 mg/kg/day in 3 divided

doses) as these patients usually present with a lactate acidosis and

have begun to break down fats into fatty acids. In the analogy of

the car engine, when the fuel is improper for the engine there are

by-products produced that can decrease the performance of the

engine. One can think of carnitine as a fuel additive to help

prevent the build up of toxic by-products created by inefficient

fuel utilization.

Carnitine binds toxic-free fatty acids and organic acids. In

addition, it acts as a mitochondrial membrane stabilizer (seals

the " leaky " gasket). Often patients with mitochondrial cytopathies

have a secondary carnitine deficiency as a result of overproduction

of free fatty acids. The carnitine deficiency would be worsened by

an acute insult to the mitochondria and the metabolic machinery.

Added carnitine during the acute stage of an illness would help in

removing toxins and improving the carnitine deficiency. However,

there are situations when added carnitine may not be needed or may

potentially worsen the situation

Other Supplements: There are occasions when other supplements, in

addition to those above, may be needed. We have patients who have

severe muscle and peripheral nerve impairment when illness also

induces changes in bioenergetic homeostasis, very similar to chronic

inflammatory demyelinating

polyneuropathy. Other patients have severe movement disorders, such

as dystonia. We have found that intravenous gamma globulin (1 - 2

gm/kg in 1 or 2 doses) temporarily improves these conditions.

Although not FDA approved for these diseases, we have seen this

treatment help reverse neuropathic weakness and dystonic movements.

There is some experience with the use of creatine in patients having

mitochondrial myopathies. We have used creatine as only a short-term

treatment when trying to prevent a patient from being placed on a

breathing machine. The body adapts to long term use of creatine and

presumably its effectiveness lessens. We would only recommend these

types of treatment in consultation

with a mitochondria expert.

Conclusion

There are a few important points to remember when dealing with an

intervening illness in a person with a

mitochondrial cytopathy.

1. The patient or caregiver, along with the primary care

physician, should develop a plan of how these illnesses will be

approached ahead of time.

2. In many patients, there is little ability to compensate during

an acute illness, so early intervention and the use of IV fluids are

often warranted.

3. Once IV hydration has started, it may be necessary to stop all

attempts at feeding, allowing the bowel to rest, until the patient

begins to request fluids or food.

4. Improvement can be slower than would be expected in otherwise

healthy persons, but most patients restart oral hydration and

feeding within 12 - 24 hours of the IV fluids having begun.

5. The source of infection should be sought, and if there is a

bacterial infection, it should be treated with appropriate

antibiotics. Viral infections should not be treated with

antibiotics, as these do not work against viruses and many

antibiotics can further limit mitochondrial function.

Glossary of Terms

Sugars: a general term used to define a simple carbohydrate.

Glucose: a common sugar contained in sucrose (table sugar) or

lactose (milk sugar).

Dextrose is the pharmaceutical term for glucose.

Bioenergetic Health: a descriptive term used to define the ability

to produce an adequate supply of energy that will meet the body's

energy demands.