Guest guest Posted June 21, 2005 Report Share Posted June 21, 2005 Oh, one further question. Do you know if the ANT testing was done on fresh or frozen tissue? I know Cleveland does some testing on fresh and some testing on frozen from each biopsy. I just wondered which was used for ANT. Barbara _____ From: [mailto: ] On Behalf Of Joanne Kocourek Sent: Tuesday, June 21, 2005 9:52 AM To: Subject: RE: ANT Dr. Hoppel (Cleveland CIDDM) did the ANT diagnosis. He was so surprised that he actually has rechecked the study at least three times. It was been a positive study each time. Dr. Wallace is the ANT expert in the US. So given the girls also have identified defects in Complex I, III and IV, I decided to discuss this atypical mix with him at the conference. (He was very approachable). He said that, from his perspective, this mix is unusual and is likely the result of severely abnormal dysfunction both within the mitochondria and across the inner mitochondrial membrane. He is positive that in my girls their base defect lies within mtDNA. Dr. Shoffner is doing an evaluation of their entire mitochondrial genone and, to date, has not identified any " known " mutations or deletions, etc. One curious comment/questions he posed was, " Your daughter's are significantly affected, aren't they? " How did he know??? Funny, they look " fine " but medically are quite compromised with major organ system involvement. Barbara Seaman wheatchild@...> wrote:Joanne, Do you know if there is any genetic connection between the two defects your daughter has? In other words, is it possible that the ANT defect is secondarily causing the deficiencies found in the respiratory chain or are there two separate mutations, one for each defect? Or has this even been defined? I ask because I also have two mitochondrial defects, though different from your daughter's. You are the only other person I can remember talking about two defects in one patient, so I am interested and curious. Do you mind sharing who did the ANT defect diagnosis? Thanks. Barbara _____ From: [mailto: ] On Behalf Of Joanne Kocourek Sent: Tuesday, June 21, 2005 9:11 AM To: Subject: Re: ANT Adenine nucleotide translocators General characteristics Most abundant mitochondrial proteins Integral components of inner mitochondrial membrane Facilitate exchange of ADP and ATP between cytosol & mitochondria ohgminion rakshasis@...> wrote: Sorry, what is ANT? Thanks, RH Joanne Kocourek (mom to , lies, and ) visit us at: http://www.caringbridge.org/il/annakris Quote Link to comment Share on other sites More sharing options...
Guest guest Posted June 21, 2005 Report Share Posted June 21, 2005 Oh, this is most interesting, as I also have an FOD. I will pass on something about Dr. Wallace's work to my doctors and see how they respond. Thanks again. Much appreciated. Barbara _____ From: [mailto: ] On Behalf Of Joanne Kocourek Sent: Tuesday, June 21, 2005 10:31 AM To: Subject: RE: ANT--- PS I believe that the ANT studies are performed after the tissue has been frozen (given Dr. Hoppel repeated the studies over a year later, some of the study was definitely done using frozen tissue). The RTC studies are completed when the sample is fresh. As for ANT genetics.... increased expression of ANT-1 and ATP synthase: subunit mRNAs have been described in patients with respiratory defects resulting from mtDNA point mutations and increased mRNAs encoding cytochrome oxidase (COX IV and COX VI) were also observed. While eukaryotic cells can respond to mitochondrial dysfunction by a modulation of nuclear gene expression, evidence for signaling pathways and transcriptional mechanisms are lacking in most instances. Several studies have also questioned mt tRNA abnormalities. I honestly believe that there can be multiple genetic reasons for a particluar abnormality or mix of abnormalities. The science is just too young for a complete body of knowledge. We are positive mtDNA is responsible in my girls we just don't know where/how. Dr. Wallace recently identified a novel homogygous mt related defect for another family (with an ANT defect and FOD), so his work is continuing. Barbara Seaman wheatchild@...> wrote: Oh, one further question. Do you know if the ANT testing was done on fresh or frozen tissue? Joanne Kocourek (mom to , lies, and ) visit us at: http://www.caringbridge.org/il/annakris Quote Link to comment Share on other sites More sharing options...
Guest guest Posted June 21, 2005 Report Share Posted June 21, 2005 If you don't mind my asking, which FOD? My girls seem to have a VLCFAD (testing still in process). Dr. Cohen is also highly suspicious of GAII. Barbara Seaman wheatchild@...> wrote:Oh, this is most interesting, as I also have an FOD. I will pass on something about Dr. Wallace's work to my doctors and see how they respond. Thanks again. Much appreciated. Barbara _____ From: [mailto: ] On Behalf Of Joanne Kocourek Sent: Tuesday, June 21, 2005 10:31 AM To: Subject: RE: ANT--- PS I believe that the ANT studies are performed after the tissue has been frozen (given Dr. Hoppel repeated the studies over a year later, some of the study was definitely done using frozen tissue). The RTC studies are completed when the sample is fresh. As for ANT genetics.... increased expression of ANT-1 and ATP synthase: subunit mRNAs have been described in patients with respiratory defects resulting from mtDNA point mutations and increased mRNAs encoding cytochrome oxidase (COX IV and COX VI) were also observed. While eukaryotic cells can respond to mitochondrial dysfunction by a modulation of nuclear gene expression, evidence for signaling pathways and transcriptional mechanisms are lacking in most instances. Several studies have also questioned mt tRNA abnormalities. I honestly believe that there can be multiple genetic reasons for a particluar abnormality or mix of abnormalities. The science is just too young for a complete body of knowledge. We are positive mtDNA is responsible in my girls we just don't know where/how. Dr. Wallace recently identified a novel homogygous mt related defect for another family (with an ANT defect and FOD), so his work is continuing. Barbara Seaman wheatchild@...> wrote: Oh, one further question. Do you know if the ANT testing was done on fresh or frozen tissue? Joanne Kocourek (mom to , lies, and ) visit us at: http://www.caringbridge.org/il/annakris Quote Link to comment Share on other sites More sharing options...
Guest guest Posted June 21, 2005 Report Share Posted June 21, 2005 Are your daughters by any chance riboflavin-responsive? I don't know for sure, but I doubt it. They take relatively high doses of riboflavin and signs/symptoms have not lessened. GA II is a relatively new " physician thought " for them. Dr. Cohen suggested it a few months ago. He ruled out all of the leukodystrophies. Children's Hospital was trying to run more formal fibrooblast studies. What they completed showed a variety of abnormalities and then they ran out of cells. They are waiting for more cells from Mayo and will then redo all of the studies. Their Complex I, II and IV function ranges from 0-40% depending on the study. TO date only the isolated novel point mutation has been found and Dr. Shoffner didn't believe it was the cause of teh problem. Information regarding ANT defects is quite limited. Some of the articles are specific to ANT alone and others discuss more global implications/deficiencies. Dr. Wallace is the ANT guru! He is at UC Irvine (relocated from Emory). Joanne Kocourek (mom to , lies, and ) visit us at: http://www.caringbridge.org/il/annakris Quote Link to comment Share on other sites More sharing options...
Guest guest Posted June 21, 2005 Report Share Posted June 21, 2005 Thanks! B _____ From: [mailto: ] On Behalf Of Joanne Kocourek Sent: Tuesday, June 21, 2005 11:45 AM To: Subject: RE: ANT--- PS Are your daughters by any chance riboflavin-responsive? I don't know for sure, but I doubt it. They take relatively high doses of riboflavin and signs/symptoms have not lessened. GA II is a relatively new " physician thought " for them. Dr. Cohen suggested it a few months ago. He ruled out all of the leukodystrophies. Children's Hospital was trying to run more formal fibrooblast studies. What they completed showed a variety of abnormalities and then they ran out of cells. They are waiting for more cells from Mayo and will then redo all of the studies. Their Complex I, II and IV function ranges from 0-40% depending on the study. TO date only the isolated novel point mutation has been found and Dr. Shoffner didn't believe it was the cause of teh problem. Information regarding ANT defects is quite limited. Some of the articles are specific to ANT alone and others discuss more global implications/deficiencies. Dr. Wallace is the ANT guru! He is at UC Irvine (relocated from Emory). Joanne Kocourek (mom to , lies, and ) visit us at: http://www.caringbridge.org/il/annakris Quote Link to comment Share on other sites More sharing options...
Guest guest Posted June 21, 2005 Report Share Posted June 21, 2005 Thanks! B _____ From: [mailto: ] On Behalf Of Joanne Kocourek Sent: Tuesday, June 21, 2005 11:45 AM To: Subject: RE: ANT--- PS Are your daughters by any chance riboflavin-responsive? I don't know for sure, but I doubt it. They take relatively high doses of riboflavin and signs/symptoms have not lessened. GA II is a relatively new " physician thought " for them. Dr. Cohen suggested it a few months ago. He ruled out all of the leukodystrophies. Children's Hospital was trying to run more formal fibrooblast studies. What they completed showed a variety of abnormalities and then they ran out of cells. They are waiting for more cells from Mayo and will then redo all of the studies. Their Complex I, II and IV function ranges from 0-40% depending on the study. TO date only the isolated novel point mutation has been found and Dr. Shoffner didn't believe it was the cause of teh problem. Information regarding ANT defects is quite limited. Some of the articles are specific to ANT alone and others discuss more global implications/deficiencies. Dr. Wallace is the ANT guru! He is at UC Irvine (relocated from Emory). Joanne Kocourek (mom to , lies, and ) visit us at: http://www.caringbridge.org/il/annakris Quote Link to comment Share on other sites More sharing options...
Guest guest Posted June 21, 2005 Report Share Posted June 21, 2005 Joanne Do you know what gene was found that was homogygous. I have one at A3796G (ACC.GCC, thr.Ala,N in Complex I. Dr. Shoffner thought that since my mother also had the same defect and it was homogenious, that it was insignificant. laurie > I believe that the ANT studies are performed after the tissue has been frozen (given Dr. Hoppel repeated the studies over a year later, some of the study was definitely done using frozen tissue). The RTC studies are completed when the sample is fresh. > > As for ANT genetics.... > increased expression of ANT-1 and ATP synthase: subunit mRNAs have been described in patients with respiratory defects resulting from mtDNA point mutations and increased mRNAs encoding cytochrome oxidase (COX IV and COX VI) were also observed. While eukaryotic cells can respond to mitochondrial dysfunction by a modulation of nuclear gene expression, evidence for signaling pathways and transcriptional mechanisms are lacking in most instances. Several studies have also questioned mt tRNA abnormalities. I honestly believe that there can be multiple genetic reasons for a particluar abnormality or mix of abnormalities. The science is just too young for a complete body of knowledge. We are positive mtDNA is responsible in my girls we just don't know where/how. Dr. Wallace recently identified a novel homogygous mt related defect for another family (with an ANT defect and FOD), so his work is continuing. > > Barbara Seaman wheatchild@...> wrote: > Oh, one further question. Do you know if the ANT testing was done on fresh > or frozen tissue? > > Joanne Kocourek (mom to , lies, and ) > visit us at: http://www.caringbridge.org/il/annakris > > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted June 21, 2005 Report Share Posted June 21, 2005 Funny you should ask....it was definitely on an A-G combination. I can't remember which number and every other physician has tried to obtain a copy of the report (and I've tried to obtain a replacement copy) unsuccessfully. Our house sustaioned major water damage while we were gone several years ago and I lost alot of the paper files I had organized. --- Laurie Fitzgerald laurie.fitzgerald@...> wrote: > Joanne > > Do you know what gene was found that was homogygous. > I have one at > A3796G (ACC.GCC, thr.Ala,N in Complex I. Dr. > Shoffner thought that > since my mother also had the same defect and it was > homogenious, that > it was insignificant. > > laurie > > On 6/21/05, Joanne Kocourek servedogmom@...> > wrote: > > I believe that the ANT studies are performed after > the tissue has been frozen (given Dr. Hoppel > repeated the studies over a year later, some of the > study was definitely done using frozen tissue). The > RTC studies are completed when the sample is fresh. > > > > As for ANT genetics.... > > increased expression of ANT-1 and ATP synthase: > subunit mRNAs have been described in patients with > respiratory defects resulting from mtDNA point > mutations and increased mRNAs encoding cytochrome > oxidase (COX IV and COX VI) were also observed. > While eukaryotic cells can respond to mitochondrial > dysfunction by a modulation of nuclear gene > expression, evidence for signaling pathways and > transcriptional mechanisms are lacking in most > instances. Several studies have also questioned mt > tRNA abnormalities. I honestly believe that there > can be multiple genetic reasons for a particluar > abnormality or mix of abnormalities. The science is > just too young for a complete body of knowledge. We > are positive mtDNA is responsible in my girls we > just don't know where/how. Dr. Wallace recently > identified a novel homogygous mt related defect for > another family (with an ANT defect and FOD), so his > work is continuing. > > > > Barbara Seaman wheatchild@...> > wrote: > > Oh, one further question. Do you know if the ANT > testing was done on fresh > > or frozen tissue? > > > > Joanne Kocourek (mom to , lies, and > ) > > visit us at: > http://www.caringbridge.org/il/annakris > > > > [Non-text portions of this message have been > removed] > > > > > > > > Medical advice, information, opinions, data and > statements contained herein are not necessarily > those of the list moderators. The author of this e > mail is entirely responsible for its content. List > members are reminded of their responsibility to > evaluate the content of the postings and consult > with their physicians regarding changes in their own > treatment. > > > > Personal attacks are not permitted on the list and > anyone who sends one is automatically moderated or > removed depending on the severity of the attack. > > > > Quote Link to comment Share on other sites More sharing options...
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