RE: Possible adult mito? - LONG & poll idea

[Guest guest]

My eyes are normally glazed over, but I hope that my graduate work in

computational biochemistry helps me understand this.

I feel that my mitochondrial disease is not " textbook " , and may be

due to a genetic cause unrelated to mitochondrial mtDNA and nDNA

genes.

Yes, you are lucky to have such definition of what is going on, if I

had that much definition, I'd probably be spending my spare time

modeling the defect proteins to find a treatment for it

Some of my friends are studying protein folding - a genetic defect

can change a protein such that the binding site is changed directly

(amino acid in the binding site is altered) or such that an amino

acid not in the binding site changes the conformation of the protein,

so the binding site is affected, but not directly. So it's possible,

for example, that a modified Complex I protein (actually on of the

proteins making up Complex I) could not bind correctly to CoQ10, and

the result would be less activity (ATP produced) for each

CoQ10 " seen " .

BTW, having normal or above normal in other metabolic cycles is

probably compensation (as I'm sure you know) - one of my major

compensations seems to be lung performance - I do very well (over

100% for some test) on PFT's, enough to shock the respiratory tech

I also have high strength, but poor endurance for light exercise.

I've been too bummed about my complete lack of Complex I activity

(yet relative health) to read my muscle biopsy report in detail, but

when I first got it, I was looking up all sorts of interesting,

seemingly non-related, items found in my muscle. They all appear to

be " symptoms " , I don't have genetic info yet.

Ah, now I have an idea for a poll - along the lines of " have you had

a muscle biopsy " , " how many have you had " , " were any results

abnormal " , " did they find a mitochondrial defect " , " did they find a

mtDNA defect " " did they find a nDNA defect " - what do people think,

should I put it up (or any suggestions for other questions - how

about for reference " how many years have you had mito symptoms " ?)

How could we address people with more than one muscle biopsy - I

guess if any of them were " yes " for a question, go with that. There

are 450(!) people in this group, and I suspect many of us are

undiagnosed...

Take care,

RH

The upshot is that you have two genetic defects identified, so that

would

> > RH, I've posted this before and thought perhaps people were

getting

> tired of

> > rereading it all once again, so I mentioned the bare minimum. For

> now, I

> > will just cut and paste two paragraphs from my emergency packet

and

> if you

> > have further questions, I can answer them. Here goes:

> >

> >

> >

> > Patient has two co-existing mitochondrial disorders:

> >

> >

> >

> > 1. Carnitine Palmitoyltransferase II Deficiency. Diagnosed

1983

> by

> > Salvatore DiMauro, MD, Columbia University, New York and Herbert

> Lindsley,

> > MD, KUMC. CPT activity in muscle reduced to 10% of normal. CPT

> deficiency is

> > an inborn error in fat metabolism causing mitochondrial myopathy.

> >

> > For more information on CPT Deficiency, visit

> www.spiralnotebook.org

> >

> >

> >

> > 2. Global Mitochondrial Defect. Diagnosed 1998. Respiratory

chain

> enzymes

> > in complexes I-IV reduced to 22 - 49% of normal as determined by

> Georgirene

> > D. Vladutiu, PhD, Buffalo, NY, via muscle biopsy. Additional

> fibroblast

> > studies of nine beta-oxidation enzymes by , PhD,

> Houston, TX,

> > found all were reduced to 29-66% of normal. Underlying genetic

> defect is

> > thought to be in mitochondrial transport, possibly one of the

heat

> shock

> > proteins, but this remains undefined. The second mitochondrial

> defect is

> > thought to cause the majority of the patient's symptoms, which

> include

> > muscle weakness and pain, myoclonus, nausea, attacks of abdominal

> pain, GI

> > dysfunction, hypoglycemia, neuropathy and stroke-like events.

> >

> > For more information on respiratory chain disorders, visit

> > http://www.umdf.org/> www.umdf.org (United Mitochondrial Disease

> > Foundation)

> >

> >

> >

> >

> >

> > _____

> >

> > From:

[mailto: ]

> On Behalf

> > Of ohgminion

> > Sent: Tuesday, April 19, 2005 12:49 PM

> > To:

> > Subject: Re: Possible adult mito?

> >

> >

> >

> >

> > First, welcome to the group, a.

> >

> > But I have a question for Barbara - what do you mean you have two

> > forms of mito? Do you mean they found two genetic defects, or

> > defects in more than one complex?

> >

> > Just wondering,

> > RH

> >

> >

> >

> >

> > *

> >

> >

> >

> >

[Guest guest]

I admire anyone who actually chooses biochemistry..I have been dragged into

it kicking and screaming. Yes, have seen bits about the protein folding

stuff..wish I had friends working in the field, though I would probably

pester them to death with questions. I understand why you have questions

about what is going on it your case and hope you can eventually find more

answers too. I always think of Zora Neale Hurston's comment, " There are

years that ask questions and years that answer. " That's the way it's been

for me, but always more questions than answers, it seems.

Take care,

Barbara

ldies [mailto: ] On Behalf Of

ohgminion

Sent: Wednesday, April 20, 2005 9:20 AM

To:

Subject: Re: Possible adult mito? - LONG & poll idea

My eyes are normally glazed over, but I hope that my graduate work in

computational biochemistry helps me understand this.

I feel that my mitochondrial disease is not " textbook " , and may be

due to a genetic cause unrelated to mitochondrial mtDNA and nDNA

genes.

Yes, you are lucky to have such definition of what is going on, if I

had that much definition, I'd probably be spending my spare time

modeling the defect proteins to find a treatment for it

Some of my friends are studying protein folding - a genetic defect

can change a protein such that the binding site is changed directly

(amino acid in the binding site is altered) or such that an amino

acid not in the binding site changes the conformation of the protein,

so the binding site is affected, but not directly. So it's possible,

for example, that a modified Complex I protein (actually on of the

proteins making up Complex I) could not bind correctly to CoQ10, and

the result would be less activity (ATP produced) for each

CoQ10 " seen " .

BTW, having normal or above normal in other metabolic cycles is

probably compensation (as I'm sure you know) - one of my major

compensations seems to be lung performance - I do very well (over

100% for some test) on PFT's, enough to shock the respiratory tech

I also have high strength, but poor endurance for light exercise.

I've been too bummed about my complete lack of Complex I activity

(yet relative health) to read my muscle biopsy report in detail, but

when I first got it, I was looking up all sorts of interesting,

seemingly non-related, items found in my muscle. They all appear to

be " symptoms " , I don't have genetic info yet.

Ah, now I have an idea for a poll - along the lines of " have you had

a muscle biopsy " , " how many have you had " , " were any results

abnormal " , " did they find a mitochondrial defect " , " did they find a

mtDNA defect " " did they find a nDNA defect " - what do people think,

should I put it up (or any suggestions for other questions - how

about for reference " how many years have you had mito symptoms " ?)

How could we address people with more than one muscle biopsy - I

guess if any of them were " yes " for a question, go with that. There

are 450(!) people in this group, and I suspect many of us are

undiagnosed...

Take care,

RH

The upshot is that you have two genetic defects identified, so that

would

> > RH, I've posted this before and thought perhaps people were

getting

> tired of

> > rereading it all once again, so I mentioned the bare minimum. For

> now, I

> > will just cut and paste two paragraphs from my emergency packet

and

> if you

> > have further questions, I can answer them. Here goes:

> >

> >

> >

> > Patient has two co-existing mitochondrial disorders:

> >

> >

> >

> > 1. Carnitine Palmitoyltransferase II Deficiency. Diagnosed

1983

> by

> > Salvatore DiMauro, MD, Columbia University, New York and Herbert

> Lindsley,

> > MD, KUMC. CPT activity in muscle reduced to 10% of normal. CPT

> deficiency is

> > an inborn error in fat metabolism causing mitochondrial myopathy.

> >

> > For more information on CPT Deficiency, visit

> www.spiralnotebook.org

> >

> >

> >

> > 2. Global Mitochondrial Defect. Diagnosed 1998. Respiratory

chain

> enzymes

> > in complexes I-IV reduced to 22 - 49% of normal as determined by

> Georgirene

> > D. Vladutiu, PhD, Buffalo, NY, via muscle biopsy. Additional

> fibroblast

> > studies of nine beta-oxidation enzymes by , PhD,

> Houston, TX,

> > found all were reduced to 29-66% of normal. Underlying genetic

> defect is

> > thought to be in mitochondrial transport, possibly one of the

heat

> shock

> > proteins, but this remains undefined. The second mitochondrial

> defect is

> > thought to cause the majority of the patient's symptoms, which

> include

> > muscle weakness and pain, myoclonus, nausea, attacks of abdominal

> pain, GI

> > dysfunction, hypoglycemia, neuropathy and stroke-like events.

> >

> > For more information on respiratory chain disorders, visit

> > http://www.umdf.org/> www.umdf.org (United Mitochondrial Disease

> > Foundation)

> >

> >

> >

> >

> >

> > _____

> >

> > From:

[mailto: ]

> On Behalf

> > Of ohgminion

> > Sent: Tuesday, April 19, 2005 12:49 PM

> > To:

> > Subject: Re: Possible adult mito?

> >

> >

> >

> >

> > First, welcome to the group, a.

> >

> > But I have a question for Barbara - what do you mean you have two

> > forms of mito? Do you mean they found two genetic defects, or

> > defects in more than one complex?

> >

> > Just wondering,

> > RH

> >

> >

> >

> >

> > *

> >

> >

> >

> >

[Guest guest]

I admire anyone who actually chooses biochemistry..I have been dragged into

it kicking and screaming. Yes, have seen bits about the protein folding

stuff..wish I had friends working in the field, though I would probably

pester them to death with questions. I understand why you have questions

about what is going on it your case and hope you can eventually find more

answers too. I always think of Zora Neale Hurston's comment, " There are

years that ask questions and years that answer. " That's the way it's been

for me, but always more questions than answers, it seems.

Take care,

Barbara

ldies [mailto: ] On Behalf Of

ohgminion

Sent: Wednesday, April 20, 2005 9:20 AM

To:

Subject: Re: Possible adult mito? - LONG & poll idea

My eyes are normally glazed over, but I hope that my graduate work in

computational biochemistry helps me understand this.

I feel that my mitochondrial disease is not " textbook " , and may be

due to a genetic cause unrelated to mitochondrial mtDNA and nDNA

genes.

Yes, you are lucky to have such definition of what is going on, if I

had that much definition, I'd probably be spending my spare time

modeling the defect proteins to find a treatment for it

Some of my friends are studying protein folding - a genetic defect

can change a protein such that the binding site is changed directly

(amino acid in the binding site is altered) or such that an amino

acid not in the binding site changes the conformation of the protein,

so the binding site is affected, but not directly. So it's possible,

for example, that a modified Complex I protein (actually on of the

proteins making up Complex I) could not bind correctly to CoQ10, and

the result would be less activity (ATP produced) for each

CoQ10 " seen " .

BTW, having normal or above normal in other metabolic cycles is

probably compensation (as I'm sure you know) - one of my major

compensations seems to be lung performance - I do very well (over

100% for some test) on PFT's, enough to shock the respiratory tech

I also have high strength, but poor endurance for light exercise.

I've been too bummed about my complete lack of Complex I activity

(yet relative health) to read my muscle biopsy report in detail, but

when I first got it, I was looking up all sorts of interesting,

seemingly non-related, items found in my muscle. They all appear to

be " symptoms " , I don't have genetic info yet.

Ah, now I have an idea for a poll - along the lines of " have you had

a muscle biopsy " , " how many have you had " , " were any results

abnormal " , " did they find a mitochondrial defect " , " did they find a

mtDNA defect " " did they find a nDNA defect " - what do people think,

should I put it up (or any suggestions for other questions - how

about for reference " how many years have you had mito symptoms " ?)

How could we address people with more than one muscle biopsy - I

guess if any of them were " yes " for a question, go with that. There

are 450(!) people in this group, and I suspect many of us are

undiagnosed...

Take care,

RH

The upshot is that you have two genetic defects identified, so that

would

> > RH, I've posted this before and thought perhaps people were

getting

> tired of

> > rereading it all once again, so I mentioned the bare minimum. For

> now, I

> > will just cut and paste two paragraphs from my emergency packet

and

> if you

> > have further questions, I can answer them. Here goes:

> >

> >

> >

> > Patient has two co-existing mitochondrial disorders:

> >

> >

> >

> > 1. Carnitine Palmitoyltransferase II Deficiency. Diagnosed

1983

> by

> > Salvatore DiMauro, MD, Columbia University, New York and Herbert

> Lindsley,

> > MD, KUMC. CPT activity in muscle reduced to 10% of normal. CPT

> deficiency is

> > an inborn error in fat metabolism causing mitochondrial myopathy.

> >

> > For more information on CPT Deficiency, visit

> www.spiralnotebook.org

> >

> >

> >

> > 2. Global Mitochondrial Defect. Diagnosed 1998. Respiratory

chain

> enzymes

> > in complexes I-IV reduced to 22 - 49% of normal as determined by

> Georgirene

> > D. Vladutiu, PhD, Buffalo, NY, via muscle biopsy. Additional

> fibroblast

> > studies of nine beta-oxidation enzymes by , PhD,

> Houston, TX,

> > found all were reduced to 29-66% of normal. Underlying genetic

> defect is

> > thought to be in mitochondrial transport, possibly one of the

heat

> shock

> > proteins, but this remains undefined. The second mitochondrial

> defect is

> > thought to cause the majority of the patient's symptoms, which

> include

> > muscle weakness and pain, myoclonus, nausea, attacks of abdominal

> pain, GI

> > dysfunction, hypoglycemia, neuropathy and stroke-like events.

> >

> > For more information on respiratory chain disorders, visit

> > http://www.umdf.org/> www.umdf.org (United Mitochondrial Disease

> > Foundation)

> >

> >

> >

> >

> >

> > _____

> >

> > From:

[mailto: ]

> On Behalf

> > Of ohgminion

> > Sent: Tuesday, April 19, 2005 12:49 PM

> > To:

> > Subject: Re: Possible adult mito?

> >

> >

> >

> >

> > First, welcome to the group, a.

> >

> > But I have a question for Barbara - what do you mean you have two

> > forms of mito? Do you mean they found two genetic defects, or

> > defects in more than one complex?

> >

> > Just wondering,

> > RH

> >

> >

> >

> >

> > *

> >

> >

> >

> >

[Guest guest]

I tend to live one day at a time, and don't look over past years for

accomplishments or struggles, only what their impact is today.

I am grateful for the answers I have, and am trying to address

symptoms when there aren't answers for the disease. Sometimes we

have to find our own answers, or redefine the question.

I *HATE* the fact that even scientists and doctors (so

called " experts " ) don't know the right questions to ask, it's an

iterative process to find the right question. Maybe a science of

asking questions should be developed - to figure what questions to

ask and when to ask them...

Take care,

RH

> > > RH, I've posted this before and thought perhaps people were

> getting

> > tired of

> > > rereading it all once again, so I mentioned the bare minimum.

For

> > now, I

> > > will just cut and paste two paragraphs from my emergency packet

> and

> > if you

> > > have further questions, I can answer them. Here goes:

> > >

> > >

> > >

> > > Patient has two co-existing mitochondrial disorders:

> > >

> > >

> > >

> > > 1. Carnitine Palmitoyltransferase II Deficiency. Diagnosed

> 1983

> > by

> > > Salvatore DiMauro, MD, Columbia University, New York and

Herbert

> > Lindsley,

> > > MD, KUMC. CPT activity in muscle reduced to 10% of normal. CPT

> > deficiency is

> > > an inborn error in fat metabolism causing mitochondrial

myopathy.

> > >

> > > For more information on CPT Deficiency, visit

> > www.spiralnotebook.org

> > >

> > >

> > >

> > > 2. Global Mitochondrial Defect. Diagnosed 1998. Respiratory

> chain

> > enzymes

> > > in complexes I-IV reduced to 22 - 49% of normal as determined

by

> > Georgirene

> > > D. Vladutiu, PhD, Buffalo, NY, via muscle biopsy. Additional

> > fibroblast

> > > studies of nine beta-oxidation enzymes by , PhD,

> > Houston, TX,

> > > found all were reduced to 29-66% of normal. Underlying genetic

> > defect is

> > > thought to be in mitochondrial transport, possibly one of the

> heat

> > shock

> > > proteins, but this remains undefined. The second mitochondrial

> > defect is

> > > thought to cause the majority of the patient's symptoms, which

> > include

> > > muscle weakness and pain, myoclonus, nausea, attacks of

abdominal

> > pain, GI

> > > dysfunction, hypoglycemia, neuropathy and stroke-like events.

> > >

> > > For more information on respiratory chain disorders, visit

> > > http://www.umdf.org/> www.umdf.org (United Mitochondrial

Disease

> > > Foundation)

> > >

> > >

> > >

> > >

> > >

> > > _____

> > >

> > > From:

> [mailto: ]

> > On Behalf

> > > Of ohgminion

> > > Sent: Tuesday, April 19, 2005 12:49 PM

> > > To:

> > > Subject: Re: Possible adult mito?

> > >

> > >

> > >

> > >

> > > First, welcome to the group, a.

> > >

> > > But I have a question for Barbara - what do you mean you have

two

> > > forms of mito? Do you mean they found two genetic defects, or

> > > defects in more than one complex?

> > >

> > > Just wondering,

> > > RH

> > >

> > >

> > >

> > >

> > > *

> > >

> > >

> > >

> > >

[Guest guest]

I tend to live one day at a time, and don't look over past years for

accomplishments or struggles, only what their impact is today.

I am grateful for the answers I have, and am trying to address

symptoms when there aren't answers for the disease. Sometimes we

have to find our own answers, or redefine the question.

I *HATE* the fact that even scientists and doctors (so

called " experts " ) don't know the right questions to ask, it's an

iterative process to find the right question. Maybe a science of

asking questions should be developed - to figure what questions to

ask and when to ask them...

Take care,

RH

> > > RH, I've posted this before and thought perhaps people were

> getting

> > tired of

> > > rereading it all once again, so I mentioned the bare minimum.

For

> > now, I

> > > will just cut and paste two paragraphs from my emergency packet

> and

> > if you

> > > have further questions, I can answer them. Here goes:

> > >

> > >

> > >

> > > Patient has two co-existing mitochondrial disorders:

> > >

> > >

> > >

> > > 1. Carnitine Palmitoyltransferase II Deficiency. Diagnosed

> 1983

> > by

> > > Salvatore DiMauro, MD, Columbia University, New York and

Herbert

> > Lindsley,

> > > MD, KUMC. CPT activity in muscle reduced to 10% of normal. CPT

> > deficiency is

> > > an inborn error in fat metabolism causing mitochondrial

myopathy.

> > >

> > > For more information on CPT Deficiency, visit

> > www.spiralnotebook.org

> > >

> > >

> > >

> > > 2. Global Mitochondrial Defect. Diagnosed 1998. Respiratory

> chain

> > enzymes

> > > in complexes I-IV reduced to 22 - 49% of normal as determined

by

> > Georgirene

> > > D. Vladutiu, PhD, Buffalo, NY, via muscle biopsy. Additional

> > fibroblast

> > > studies of nine beta-oxidation enzymes by , PhD,

> > Houston, TX,

> > > found all were reduced to 29-66% of normal. Underlying genetic

> > defect is

> > > thought to be in mitochondrial transport, possibly one of the

> heat

> > shock

> > > proteins, but this remains undefined. The second mitochondrial

> > defect is

> > > thought to cause the majority of the patient's symptoms, which

> > include

> > > muscle weakness and pain, myoclonus, nausea, attacks of

abdominal

> > pain, GI

> > > dysfunction, hypoglycemia, neuropathy and stroke-like events.

> > >

> > > For more information on respiratory chain disorders, visit

> > > http://www.umdf.org/> www.umdf.org (United Mitochondrial

Disease

> > > Foundation)

> > >

> > >

> > >

> > >

> > >

> > > _____

> > >

> > > From:

> [mailto: ]

> > On Behalf

> > > Of ohgminion

> > > Sent: Tuesday, April 19, 2005 12:49 PM

> > > To:

> > > Subject: Re: Possible adult mito?

> > >

> > >

> > >

> > >

> > > First, welcome to the group, a.

> > >

> > > But I have a question for Barbara - what do you mean you have

two

> > > forms of mito? Do you mean they found two genetic defects, or

> > > defects in more than one complex?

> > >

> > > Just wondering,

> > > RH

> > >

> > >

> > >

> > >

> > > *

> > >

> > >

> > >

> > >

[Guest guest]

Amen to all.

B

_____

From: [mailto: ] On Behalf

Of ohgminion

Sent: Wednesday, April 20, 2005 10:17 AM

To:

Subject: Re: Possible adult mito? - LONG & poll idea

I tend to live one day at a time, and don't look over past years for

accomplishments or struggles, only what their impact is today.

I am grateful for the answers I have, and am trying to address

symptoms when there aren't answers for the disease. Sometimes we

have to find our own answers, or redefine the question.

I *HATE* the fact that even scientists and doctors (so

called " experts " ) don't know the right questions to ask, it's an

iterative process to find the right question. Maybe a science of

asking questions should be developed - to figure what questions to

ask and when to ask them...

Take care,

RH

> > > RH, I've posted this before and thought perhaps people were

> getting

> > tired of

> > > rereading it all once again, so I mentioned the bare minimum.

For

> > now, I

> > > will just cut and paste two paragraphs from my emergency packet

> and

> > if you

> > > have further questions, I can answer them. Here goes:

> > >

> > >

> > >

> > > Patient has two co-existing mitochondrial disorders:

> > >

> > >

> > >

> > > 1. Carnitine Palmitoyltransferase II Deficiency. Diagnosed

> 1983

> > by

> > > Salvatore DiMauro, MD, Columbia University, New York and

Herbert

> > Lindsley,

> > > MD, KUMC. CPT activity in muscle reduced to 10% of normal. CPT

> > deficiency is

> > > an inborn error in fat metabolism causing mitochondrial

myopathy.

> > >

> > > For more information on CPT Deficiency, visit

> > www.spiralnotebook.org

> > >

> > >

> > >

> > > 2. Global Mitochondrial Defect. Diagnosed 1998. Respiratory

> chain

> > enzymes

> > > in complexes I-IV reduced to 22 - 49% of normal as determined

by

> > Georgirene

> > > D. Vladutiu, PhD, Buffalo, NY, via muscle biopsy. Additional

> > fibroblast

> > > studies of nine beta-oxidation enzymes by , PhD,

> > Houston, TX,

> > > found all were reduced to 29-66% of normal. Underlying genetic

> > defect is

> > > thought to be in mitochondrial transport, possibly one of the

> heat

> > shock

> > > proteins, but this remains undefined. The second mitochondrial

> > defect is

> > > thought to cause the majority of the patient's symptoms, which

> > include

> > > muscle weakness and pain, myoclonus, nausea, attacks of

abdominal

> > pain, GI

> > > dysfunction, hypoglycemia, neuropathy and stroke-like events.

> > >

> > > For more information on respiratory chain disorders, visit

> > > http://www.umdf.org/> www.umdf.org (United Mitochondrial

Disease

> > > Foundation)

> > >

> > >

> > >

> > >

> > >

> > > _____

> > >

> > > From:

> [mailto: ]

> > On Behalf

> > > Of ohgminion

> > > Sent: Tuesday, April 19, 2005 12:49 PM

> > > To:

> > > Subject: Re: Possible adult mito?

> > >

> > >

> > >

> > >

> > > First, welcome to the group, a.

> > >

> > > But I have a question for Barbara - what do you mean you have

two

> > > forms of mito? Do you mean they found two genetic defects, or

> > > defects in more than one complex?

> > >

> > > Just wondering,

> > > RH

> > >

> > >

> > >

> > >

> > > *

> > >

> > >

> > >

> > >