Re: Skin Fibroblast Studies

[Guest guest]

We returned from clinic visits at Mayo Clinic last night. I did have the

opportunity to ask Dr. Whiteman specifically about the best way for families to

have formal skin fibroblast studies completed (if they are not patients at Mayo

Clinic). He provvided information sheets that I would be happy to fax to anyone

that is interested with the specific ordering information. Mayo Clinic Lab runs

Mitochondrial Respiratory Chain Complex Profiles on skin fibroblasts. He said

the ideal is to have the skin tissue sample taken and grown locally, then to

have the lab forward some of the dcells fo ranalysis. That way the originating

center has additional cells if more are needed. else a sample can bne taken and

shipped immediately (the order codes are different). Then Mayo grows the cells

and maintains the sample. The challenge with this route is getting the cells to

Mayo quickly enough that they are viable for growth and analysis. He indicated

that often the cells are damaged in transit

and then Mayo has nothing or a suboptimal specimen to work with. If you are

interested in having me fax a copy of the ordering information from Mayo, please

send me a private post with your fax number. NOTE: A skin fibroblast study may

or may not be able to yield a diagnosis, but it is one study that is far less

invasive than a muscle biopsy. If the result is positive, you may be spared a

muscle biopsy. If it is negative, a muscle biopsy may still be indicated if

mitochondrial disease is suspected.

Generally cell samples are grown locally and split. He typically suggests that

cells be evaluated for both mitochondrial function and FOD related analysis. My

girls had their FOD analysis completed (and now being redone with newer

technology) at Children's Hospital of Wisconsin in Bill Rhead's lab at Dr.

Whiteman's request. Bill's lab is also supposed to be superb in conducting

analysis for carnitine related dysfunction as well.

The following is some of the general contact information for both the Mayo Lab

and Dr. Rhead's Lab.

Mayo Medical Laboratories (Rochester, MN)

Mayo Clinic Biochemical Genetics Laboratory

Phone: for Supplemental Diagnostic testing/Consultation

Fax:

Co-Directors: Dietrich Matern, MD, FACMG matern@... and Piero Rinaldo*, MD,

PhD, FACMG rinaldo@...

Website:http://www.mayoclinic.org/laboratorygenetics-rst/newbornscreening.html

Please note that approximately 35 disorders of fatty acid, amino acid, and

organic acid metabolism are included in the Supplemental Newborn Screen (SNS).

Your physician, hospital, or hospital laboratory must arrange for SNS testing,

including requesting screening cards and submitting samples to Mayo. Mayo is

unable to accept specimens directly from patients or families. Mayo works

directly with health care providers and laboratories who may contact Mayo to

arrange for SNS testing for their patients by calling 1-.

Metabolism Clinic Appointments for patients who wish to be seen in consultation

at Mayo Clinic

Whiteman* MD

Appointments:

Fax:

[Please note: Self-referrals are accepted at Mayo, however, we cannot make

specific clinical recommendations prior to evaluating you or your child. It is

very helpful to have your primary physician contact us and send a referral

summary and relevant laboratory reports. With this information, we may be able

to provide your physician with some guidance if necessary prior to your

evaluation.]

Labs that perform FOD Diagnostic Testing, Research and/or Consultation

[Note: Each Lab has their own procedures for diagnostic testing and which

specific FODs may be tested, researched, and/or clinically treated. Some Labs

only perform diagnostics, but others may offer onsite clinical

evaluation/treatment (and possibly emergency phone consultation) by physicians

experienced with FODs. Please have your physician contact the specific Lab to

determine what services they can provide. Please note that professionals on both

lists with an * next to their name have listed on a Professional Questionnaire

that families may contact them or their staff directly via email and/or phone.

If for some reason their policies change, however, have your physician contact

them for information.]

Medical College of Wisconsin - Fatty Acid Oxidation Disorder Lab (Milwaukee, WI)

Rhead*, MD, PhD, Director

wrhead@...

Phone:

Website:

http://www.chw.org/display/PPF/DocID/9972/router.asp

FODs Addressed At This Site

Carnitine Transport Defect (Primary Carnitine Deficiency)

Carnitine-Acylcarnitine Translocase Deficiency (Translocase)

Carnitine Palmitoyl Transferase I & II (CPT I & II) Deficiency

Very Long Chain Acyl-CoA Dehydrogenase (VLCAD) Deficiency

Long Chain 3-Hydroxyacyl-CoA Dehydrogenase (LCHAD) Deficiency

Trifunctional Protein (TFP) Deficiency

Medium Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency

2,4 Dienoyl-CoA Reductase Deficiency

Short Chain Acyl-CoA Dehydrogenase (SCAD) Deficiency

Short Chain L-3-Hydroxyacyl-CoA Dehydrogenase (SCHAD) Deficiency

Electron Transfer Flavoprotein (ETF) Dehydrogenase Deficiency (GAII & MADD)

3-Hydroxy-3 Methylglutaryl-CoA Lyase Deficiency (HMG)

Unclassified FODs

Joanne Kocourek (mom to , lies, and )

visit us at: http://www.caringbridge.org/il/annakris

[Guest guest]

I understand that if you have two sets of conflicting results, you

might want to run more tests, but what caused you to doubt the

results of the first test? Because they were looking for similar

issues with both daughters

When you say " different " , do you mean different complexes showing up

as affected or unaffected, or different microscopic changes (RRF

present or not, abnormal numbers or shapes of mitochondria)? Did the

different results lead to a change in treatment for either of your

daughters? I could understand getting different numbers for %

activity of a particular complex, but not having 0% and 95% activity

for the same complex in different tests (or is that possible?).

Sorry for all the questions, I've had one muscle biopsy that I've

been assuming is " mostly " correct, but since I have a son affected, I

am wondering myself about how definite one test is (but how would

more tests help?).

Thanks,

RH

> Joanne, Thanks for sharing this information. The FOD lab at the

Medical

> College of Wisconsin worked on my tissue and my son's about 15

years ago on

> a research basis (not for diagnosis which we already had). They were

> specifically looking at variations upon carnitine, CPT, ATP and

nucleotides

> via muscle. Dr. Wortmann was there at the time and was the

research

> person working on our family stuff. Not sure if Dr. Rhead was there

at that

> point or if he was involved, but I'm glad to know they are still

doing good

> work on FODs.

>

>

>

> It sounds like Mayo is still saying that OXPHOS diagnosis by

fibroblast

> analysis of enzyme activity is iffy. It may or may not reveal a

> mitochondrial respiratory chain disorder. At least that's what I

hear in

> what you've posted. This would fit with what I've been told from

other

> experts. Fibroblasts are definitely more useful in FODs.

>

>

>

> Barbara

>

>

>

> _____

>

> From: [mailto: ]

On Behalf

> Of Joanne Kocourek

> Sent: Thursday, June 30, 2005 11:35 AM

> To:

> Subject: Re: Skin Fibroblast Studies

>

>

>

>

> We returned from clinic visits at Mayo Clinic last night. I did

have the

> opportunity to ask Dr. Whiteman specifically about the best way for

families

> to have formal skin fibroblast studies completed (if they are not

patients

> at Mayo Clinic). He provvided information sheets that I would be

happy to

> fax to anyone that is interested with the specific ordering

information.

> Mayo Clinic Lab runs Mitochondrial Respiratory Chain Complex

Profiles on

> skin fibroblasts. He said the ideal is to have the skin tissue

sample taken

> and grown locally, then to have the lab forward some of the dcells

fo

> ranalysis. That way the originating center has additional cells if

more are

> needed. else a sample can bne taken and shipped immediately (the

order

> codes are different). Then Mayo grows the cells and maintains the

sample.

> The challenge with this route is getting the cells to Mayo quickly

enough

> that they are viable for growth and analysis. He indicated that

often the

> cells are damaged in transit

> and then Mayo has nothing or a suboptimal specimen to work with.

If you are

> interested in having me fax a copy of the ordering information from

Mayo,

> please send me a private post with your fax number. NOTE: A skin

fibroblast

> study may or may not be able to yield a diagnosis, but it is one

study that

> is far less invasive than a muscle biopsy. If the result is

positive, you

> may be spared a muscle biopsy. If it is negative, a muscle biopsy

may still

> be indicated if mitochondrial disease is suspected.

>

> Generally cell samples are grown locally and split. He typically

suggests

> that cells be evaluated for both mitochondrial function and FOD

related

> analysis. My girls had their FOD analysis completed (and now being

redone

> with newer technology) at Children's Hospital of Wisconsin in Bill

Rhead's

> lab at Dr. Whiteman's request. Bill's lab is also supposed to be

superb in

> conducting analysis for carnitine related dysfunction as well.

>

> The following is some of the general contact information for both

the Mayo

> Lab and Dr. Rhead's Lab.

>

>

>

>

> Mayo Medical Laboratories (Rochester, MN)

> Mayo Clinic Biochemical Genetics Laboratory

> Phone: for Supplemental Diagnostic

testing/Consultation

> Fax:

> Co-Directors: Dietrich Matern, MD, FACMG matern@m... and Piero

Rinaldo*,

> MD, PhD, FACMG rinaldo@m...

> Website:http://www.mayoclinic.org/laboratorygenetics-

rst/newbornscreening.ht

> ml

>

> Please note that approximately 35 disorders of fatty acid, amino

acid, and

> organic acid metabolism are included in the Supplemental Newborn

Screen

> (SNS). Your physician, hospital, or hospital laboratory must

arrange for SNS

> testing, including requesting screening cards and submitting

samples to

> Mayo. Mayo is unable to accept specimens directly from patients or

families.

> Mayo works directly with health care providers and laboratories who

may

> contact Mayo to arrange for SNS testing for their patients by

calling

> 1-.

>

> Metabolism Clinic Appointments for patients who wish to be seen in

> consultation at Mayo Clinic

> Whiteman* MD

> Appointments:

> Fax:

> [Please note: Self-referrals are accepted at Mayo, however, we

cannot make

> specific clinical recommendations prior to evaluating you or your

child. It

> is very helpful to have your primary physician contact us and send a

> referral summary and relevant laboratory reports. With this

information, we

> may be able to provide your physician with some guidance if

necessary prior

> to your evaluation.]

>

>

> Labs that perform FOD Diagnostic Testing, Research and/or

Consultation

>

> [Note: Each Lab has their own procedures for diagnostic testing and

which

> specific FODs may be tested, researched, and/or clinically treated.

Some

> Labs only perform diagnostics, but others may offer onsite clinical

> evaluation/treatment (and possibly emergency phone consultation) by

> physicians experienced with FODs. Please have your physician

contact the

> specific Lab to determine what services they can provide. Please

note that

> professionals on both lists with an * next to their name have

listed on a

> Professional Questionnaire that families may contact them or their

staff

> directly via email and/or phone. If for some reason their policies

change,

> however, have your physician contact them for information.]

>

>

>

> Medical College of Wisconsin - Fatty Acid Oxidation Disorder Lab

(Milwaukee,

> WI)

> Rhead*, MD, PhD, Director

> wrhead@m...

> Phone:

> Website:

>

> http://www.chw.org/display/PPF/DocID/9972/router.asp

>

>

>

> FODs Addressed At This Site

>

> Carnitine Transport Defect (Primary Carnitine Deficiency)

> Carnitine-Acylcarnitine Translocase Deficiency (Translocase)

> Carnitine Palmitoyl Transferase I & II (CPT I & II) Deficiency

> Very Long Chain Acyl-CoA Dehydrogenase (VLCAD) Deficiency

> Long Chain 3-Hydroxyacyl-CoA Dehydrogenase (LCHAD) Deficiency

> Trifunctional Protein (TFP) Deficiency

> Medium Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency

> 2,4 Dienoyl-CoA Reductase Deficiency

> Short Chain Acyl-CoA Dehydrogenase (SCAD) Deficiency

> Short Chain L-3-Hydroxyacyl-CoA Dehydrogenase (SCHAD) Deficiency

> Electron Transfer Flavoprotein (ETF) Dehydrogenase Deficiency

(GAII &

> MADD)

> 3-Hydroxy-3 Methylglutaryl-CoA Lyase Deficiency (HMG)

> Unclassified FODs

>

>

>

>

>

>

>

>

>

>

>

>

> Joanne Kocourek (mom to , lies, and )

> visit us at: http://www.caringbridge.org/il/annakris

>

>

[Guest guest]

I think (at least) another mitoldie has gone through this issue with

Child Protective Services accusing them of " Munchausen by Proxy " . As

adults, many, if not all, of us have had doctors and/or family

members tell us that we were " making up symptoms " or it's " all in our

heads " .

Thank you for answering my questions, and two comments. One is that

if they test different areas, they might find different complex

activities. Another thing is that Dr. Shoffner's office told us that

if there is a problem in Complex I, it might " trickle down " to the

other complexes. I show a " partial defect " in the activity of

Complex III, but the lab results and report indicate that it is

probably due to my lack of activity in Complex I.

Once again, thanks for sharing the info

Take care,

RH

> Hi,

>

> No easy answers but I will try....

>

test? > I didn't, but two events pushed the decision

> to biopsy both (vs one child) and later to rebiopsy.

> First, we had a numebr of physicians that flatly

> refused to treat one child based upon the other

> child's positive pathology. Then, an influencial

> physician refused to accept the positive pathology

> from Atlanta, with differing pathology in the other

> child, and called protective services, stating that

> we, as parents, were " making the girls ill " . The

> State basically demanded verification of diagnosis.

>

> > When you say " different " , do you mean different

> > complexes , or different microscopic

> > changes (RRF present or not, abnormal numbers or

> shapes of mitochondria)?> Different as in differing

> defects, between all of the pathology reports, the

> girls have defects or deficiencies in Complex I, III,

> IV and ANT. Not only do they show different defects,

> but different percentages of abnormality.

>

>

treatment for either of your daughters? > Yes, they

> have modified both treatment and additional testing

> based upon the differing results. And, more

> complexing to some physicians, their response to the

> different changes has been interesting. Many of the

> changes have lead to at least short term improvement.

>

> I could understand getting different numbers for %

> > activity of a particular complex, but not having 0%

> > and 95% activity for the same complex in different

> tests (or is that possible?).> This is EXACTLY what

> happened. One biopsy showeed 0% Complex I, the next

> completely NORMAL Complex I, but a partial defect in

> Complex III and IV. In our other daughter, one showed

> a complete defect in ANT with normal everything else,

> and the next study showed defects in Complex I, the

> next defects in III and IV.

>

> > (but how would more tests help?).> In all honestly

> if it weren't for the problems with protective

> services and challenging, ignorant physicians we would

> have NEVER done any additional diagnostic testing. It

> was the only way to keep our family together. Even

> with all of the studies we have, some physicians still

> continue to refute the diagnosis and/or deny the

> presence of symptoms, necessary treatment, etc. At

> this pooint, I do my level headed best to avoid those

> docs and limit their visits to physicians who are

> knowledgeable, understanding and willing to offer

> supportive treatment and care. We ended up seeing

> Dr., Whiteman and Dr. Cohen because that is the

> combination of expertice that was required for us to

> keep our family intact. They seem to have a good

> working relationship and every consult note reconfirms

> the diagnosis with supportive medical reports.

> >

>

>

> Joanne Kocourek (mom to , lies, and )

> visit us at: http://www.caringbridge.org/il/annakris