Guest guest Posted September 8, 2005 Report Share Posted September 8, 2005 > ----- Original Message ----- > From: klaga5 >> Hi, I got my results from Athena for the > mitochondrial genetic tests. > They were negative. I assume that rules them out. > Have any of you > had them turn out negative, then had a biopsy say > otherwise? > Are you talking about blood tests? Serum genetic testing is positive in only about 3% of disorders. The thing is that they know little about mito and it's tough to get a diagnosis. Hey, we're at seven years of trying---and we're still at the beginning. Mom to the two best kids in the world! http://www.caringbridge.org/visit/thomasandkatie ______________________________________________________ Click here to donate to the Hurricane Katrina relief effort. http://store.yahoo.com/redcross-donate3/ Quote Link to comment Share on other sites More sharing options...
Guest guest Posted September 8, 2005 Report Share Posted September 8, 2005 Hi Kim, You've already gotten a lot of replies and they fit my experience. Athena screens for certain known mitochondrial mutations. A negative result does not rule out mitochondrial disease, it only means that you do not carry any of the specific mitochondrial mutations in the Athena list. Your doctor should have explained this to you when he gave you the test results. Most labs have certain mutations that their technicians are trained to screen for, and this list is limited and in no way includes all known mitochondrial mutations. Usually a lab like Athena will screen for the most common known mutations. In addition to this list of more common mutations, there are many other known mutations that were not included in your screening. No one lab screens for every known mitochondrial mutation. And beyond the known mutations, there are many mutations that have not yet been discovered. Mito science is in its infancy, which means genetic screening may, in a few cases, hit the jackpot and find the specific mutation that is causing the patient's symptoms. But in most cases, this doesn't happen. There are simply too many mitochondrial mutations that have not yet been discovered and are not even in the lists for screening. To make it even more difficult, some mutations can be private, that is, they are found only in one family. In our family, researchers did find the causative mutation for our CPT deficiency, R503C, but it was a new one at that point (1998) and was first found in our family. Three people in my family carry it and they have since found it in one other family. Screening for common CPT mutations turned up nothing because we don't have the more common mutations. Those who want to read further about genetic screening in the diagnosis of mitochondrial respiratory chain disorders might be interested in this article. Two excerpts below. http://www.rgbgl.org/research/respiratorychain.htm Barbara -------- Genetic testing for mitochondrial disorders: " I predict that only in a minority of cases will we be fortunate enough to find a single gene defect (mitochondrial DNA or nuclear DNA) that is causative. In fact, in a published study of 2,000 specimens referred for mtDNA mutation analysis, Dr. Lee-Jun Wong's laboratory found a causative mutation in under 7%. This ballpark yield in large-scale studies has been echoed in at least 2 other laboratories. " Supplements and biopsies: " We have had the opportunity to study a handful patient biopsies before and after the patients received vitamin/cofactor therapy. The enzyme activities were generally higher during therapy compared with being off therapy. I always recommend that patients not be on cofactor therapy at the time of biopsy if possible. At the very least, if they are on cofactors I would like to have that information and may factor it into my interpretation of the quantitative data. " > athena mito results > > Hi, I got my results from Athena for the mitochondrial genetic tests. > They were negative. I assume that rules them out. Have any of you > had them turn out negative, then had a biopsy say otherwise? Quote Link to comment Share on other sites More sharing options...
Guest guest Posted September 8, 2005 Report Share Posted September 8, 2005 > Hi, I got my results from Athena for the mitochondrial genetic tests. > They were negative. I assume that rules them out. Have any of you > had them turn out negative, then had a biopsy say otherwise? I've had both the genetic blood tests and genetic sequencing, by Shoffner's lab, and they were all negative. On the other hand, the biochemical testing was much different, I have a complete lack of activity in Complex I when my muscle was tested. I am considered a " MELAS phenotype " that is my symptoms match MELAS pretty well, but have no genetic markers that have been identified. There are almost literally an infinite number of genetic mutations possible in a person, and a few may lead to a genetic disease. I get the impression that this area isn't fully developed yet, so the only response I had to my negative genetic sequencing result is that it's a shame because now my son (who shows symptoms) can't be tested for whatever my genetic defect might be. > I'm still waiting on the electron microscope study of my 2nd muscle > biopsy. Because some of my cells have central nucleus, and some > other abnormalities, there's a chance I have > centronuclear/myotubular myopathy. If I do, the electron > microscope study should be able to diagnose it. > > I'm now at three years of trying to find a diagnosis. If my > symptoms hadn't been blamed on my bad heart valve, I'm sure it > would have been looked into and diagnosed long ago. I try to > ignore this whole situation, and just live life. I suppose that's > why I don't read or post to the list much. If you read this site, you'll see that many of us " just live life " , but try to find a bit of assistance or support through other people's experiences. > With the negative genetic tests, I guess I should say goodbye to > this list. Thank you all for your support. It really has helped. Uh, see my notes above. ALL of my genetic testing, including sequencing which is very detailed, are negative. Yet Horizon Molecular Medicine showed that the activity of Complex I was ZERO, indicating a mitochondrial disease. The doctors definitely don't have all the answers for this group of diseases. Note that I had some odd macroscopic abnormalities on my cells that are indicative of other things going on, I don't think they rule out mito, just part of the " mystery " . If you think you " could " have mito, you might want to talk to a doctor about starting some supplements to see if you have improvement. Take care, RH Quote Link to comment Share on other sites More sharing options...
Guest guest Posted September 8, 2005 Report Share Posted September 8, 2005 My primary doc doesn't want to give me anything without a diagnosis. My MDA doc is out of ideas. I'll just have to find a way to get to Atlanta. I'm thankful they're willing to see me. Kim > If you think you " could " have > mito, you might want to talk to a doctor about starting some > supplements to see if you have improvement. > > Take care, > RH Quote Link to comment Share on other sites More sharing options...
Guest guest Posted September 8, 2005 Report Share Posted September 8, 2005 --- klaga5 klaga5@...> wrote: > RH, > I still don't really understand it I guess. Complex > I doesn't show > up on genetic tests? Very little shows up on genetic tests---about three percent can be diagnosed that way. We're starting my son on supplements with only a metabolic disorder, NOS diagnosis. You can do that. Everything (but carnitor) is OTC. Responsiveness to the cocktail strongly suggests mito even in the face of other non-diagnostic test. Mom to the two best kids in the world! http://www.caringbridge.org/visit/thomasandkatie __________________________________________________ Quote Link to comment Share on other sites More sharing options...
Guest guest Posted September 8, 2005 Report Share Posted September 8, 2005 Kim, I don't how long you have been in the testing process. I know how it must feel in the waiting game, as I have been there also. It is a horrible situation to be in, when you do not know what exactly you suffer from. Albeit it would be much simpler if Mito had a definitive test. It would certainly cut down the amount of wait time. It took 8 agonizing years before a doctor at Froedtert gave me the diagnosis of Mitochondrial Myopathy. He still feels I have MELAS despite what 2 common genetic types proved negative. It is a sad state of affairs when the doctors throw their hands in the air, saying they have exhausted their options. (Been there, done that many times) I'll be praying the diagnosis does not pull the " Mito name " out of its hat. Wishing you the best- Ann Re: athena mito results > > > > Barbara, > > Of course I would have prefered that it was a definative test > > result, but I want the truth. I guess I'd better accept I'll need > > to go to Atlanta. At least it'll probably represent the end of > > testing. Hopefully it'll mean a diagnosis too. > > Thanks for the info. > > Kim > > 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...
Guest guest Posted September 8, 2005 Report Share Posted September 8, 2005 Hi Kim I would like to know what the full panel involves, can you explain or point me to a place where it is described? Thanks, Lene Subject: Re: athena mito results Did they only test for melas or did they do the full mito panel? (mine was the full panel) Kim Quote Link to comment Share on other sites More sharing options...
Guest guest Posted September 8, 2005 Report Share Posted September 8, 2005 > I still don't really understand it I guess. Complex I doesn't show > up on genetic tests? Sorry if that's a dumb question. > Kim Not a dumb question at all. Think of your DNA as a blueprint or recipe for building proteins. If the recipe for the proteins in complex I are written correctly in your DNA, then complex I will be normal---like a cake recipe that turns out right. If there is a mistake in the recipe, the proteins in complex I may be missing or damaged--and the cake falls flat. That means there are two ways to diagnose a mitochondrial disease like complex I deficiency. 1. You can look for the mistake in the recipe---the disease-causing mutation--the " mis-spelled " part of the genetic code that contains the instructions for complex I. 2. Or you can look at the fallen cake, measure the biochemical ingredients of the cake and figure out which protein is damaged or missing. Given our current technology, we are better at #2 than #1. Most often #2 is the best bet for diagnosis. In this case, the " fallen cake " is muscle. So they take a piece of muscle and measure it biochemically (using enzyme assays) to see if complex I is present in normal amounts. If not, that confirms the diagnosis. But scientists being of a scientific mind, they like to get to the bottom of the story. The bottom of the story in genetic disease is in the DNA. There are many different kinds of " mis-spellings " in the genetic code for complex I that can cause complex I to be damaged or missing. These mutations or changes are given individual names---strings of letters and numbers that make a sort of " address " which identifies where the mutation is in the DNA and what kind of " mis-spelling " occurred at that location. Because there are so many different kinds of mutations or " mis-spellings " just for complex I, many have not been identified yet. So your chances of getting a diagnosis by looking at the recipe are slim, at least for now. The science just isn't there yet. Still, it can be worth checking. Best bet is looking at the fallen cake and identifying which biochemical ingredient is missing, which is the way most people in this group have gotten a diagnosis. This analogy greatly simplifies everything, of course, but was the best thing I could think of at the moment. Barbara Quote Link to comment Share on other sites More sharing options...
Guest guest Posted September 8, 2005 Report Share Posted September 8, 2005 We enjoyed Atlanta, and went to Disneyworld first to make a bit of a vacation out of it, then drove to Atlanta. I was close to going to C- P in NYC, very close to where I live, but people on this list convinced me otherwise (well, not " not " to go to NYC, just that Atlanta seemed to work out for several people who had had biospies elsewhere). We were able to schedule within a few months, and got out-of-network coverage for the fresh muscle biopsy because no one in network could do it. Take care, RH > > Hi Kim, > > > > You've already gotten a lot of replies and they fit my experience. > Athena > > screens for certain known mitochondrial mutations. A negative > result does > > not rule out mitochondrial disease, it only means that you do not > carry any > > of the specific mitochondrial mutations in the Athena list. Your > doctor > > should have explained this to you when he gave you the test > results. > > > > Most labs have certain mutations that their technicians are > trained to > > screen for, and this list is limited and in no way includes all > known > > mitochondrial mutations. Usually a lab like Athena will screen for > the most > > common known mutations. > > > > In addition to this list of more common mutations, there are many > other > > known mutations that were not included in your screening. No one > lab screens > > for every known mitochondrial mutation. And beyond the known > mutations, > > there are many mutations that have not yet been discovered. > > > > Mito science is in its infancy, which means genetic screening may, > in a few > > cases, hit the jackpot and find the specific mutation that is > causing the > > patient's symptoms. But in most cases, this doesn't happen. There > are simply > > too many mitochondrial mutations that have not yet been discovered > and are > > not even in the lists for screening. To make it even more > difficult, some > > mutations can be private, that is, they are found only in one > family. > > > > In our family, researchers did find the causative mutation for our > CPT > > deficiency, R503C, but it was a new one at that point (1998) and > was first > > found in our family. Three people in my family carry it and they > have since > > found it in one other family. Screening for common CPT mutations > turned up > > nothing because we don't have the more common mutations. > > > > Those who want to read further about genetic screening in the > diagnosis of > > mitochondrial respiratory chain disorders might be interested in > this > > article. Two excerpts below. > > http://www.rgbgl.org/research/respiratorychain.htm > > > > Barbara > > -------- > > > > Genetic testing for mitochondrial disorders: > > " I predict that only in a minority of cases will we be fortunate > enough to > > find a single gene defect (mitochondrial DNA or nuclear DNA) that > is > > causative. In fact, in a published study of 2,000 specimens > referred for > > mtDNA mutation analysis, Dr. Lee-Jun Wong's laboratory found a > causative > > mutation in under 7%. This ballpark yield in large-scale studies > has been > > echoed in at least 2 other laboratories. " > > > > Supplements and biopsies: > > " We have had the opportunity to study a handful patient biopsies > before and > > after the patients received vitamin/cofactor therapy. The enzyme > activities > > were generally higher during therapy compared with being off > therapy. I > > always recommend that patients not be on cofactor therapy at the > time of > > biopsy if possible. At the very least, if they are on cofactors I > would like > > to have that information and may factor it into my interpretation > of the > > quantitative data. " > > > > > > > athena mito results > > > > > > Hi, I got my results from Athena for the mitochondrial genetic > tests. > > > They were negative. I assume that rules them out. Have any of > you > > > had them turn out negative, then had a biopsy say otherwise? Quote Link to comment Share on other sites More sharing options...
Guest guest Posted September 8, 2005 Report Share Posted September 8, 2005 That's the beauty of some of the supplements, they don't need a prescription. I just wanted to " cover all bases " and not say " yes, go on the cocktail ASAP " , it's SOOOOOOOO frustrating because we are all so much into self-management of meds (not recommended by anyone) because of the vagaries of these illnesses. Perhaps you could email someone privately about your concerns about starting supplements on your own, although I didn't start going through " the mito cocktail " list until I had a confirmed diagnosis, I had only tried CoQ10 and Carnitor before that. Take care, RH > My primary doc doesn't want to give me anything without a diagnosis. > My MDA doc is out of ideas. I'll just have to find a way to get to > Atlanta. I'm thankful they're willing to see me. > Kim > > > If you think you " could " have > > mito, you might want to talk to a doctor about starting some > > supplements to see if you have improvement. > > > > Take care, > > RH Quote Link to comment Share on other sites More sharing options...
Guest guest Posted September 8, 2005 Report Share Posted September 8, 2005 To add to this, my understanding is that not all mitochondrial proteins (of which Complex I is one, or rather Complex I is a protein complex, more than one protein I think) are coded 100% from mtDNA (mitochondrial DNA), there is often a nDNA (nuclear DNA) component as well. Perhaps think of it, taking Barbara's analogy, as making a cake, but the cake recipe is in one book and the frosting recipe in the other book, and instructions for decorations somewhere else (i don't know, candied violets maybe?). Even the sequencing, which individually checks one's DNA versus a normal DNA, is limited because they just may not know where all the parts of the complex " come from " . Genetic blood testing takes one little bit of DNA and sees if one particular mutation is present. I have some " misspellings " in my mtDNA, but none that lead to a genetic disorder ( " normal " defects if you can imagine that). But I don't think they sequenced the nDNA portion, which is the part they suspect is messed up for me, because of the time and trouble and possibly lack of knowledge of it. The test that was very abnormal for me was one where they essentially check if Complex I can do its normal biochemical reaction. Mine couldn't. As far as how I can function with no activity (and function pretty well), the interpretation is that their test is limited in scope and doesn't put in all possible raw materials for the biochemical reaction, just a standard one that they have results for normal and affected people for. So another analogy is that the complexes are each little black boxes where you throw in a raw material, and get a product out, but they are in a line so any part could be not working to cause a problem. My first little black box didn't know what to do with the raw material given when they tested it (others please correct me if this is incorrect). Never be afraid to ask a question, the only stupid question is the one not asked... Take care, RH > > I still don't really understand it I guess. Complex I doesn't show > > up on genetic tests? Sorry if that's a dumb question. > > Kim > > Not a dumb question at all. > > Think of your DNA as a blueprint or recipe for building proteins. If the > recipe for the proteins in complex I are written correctly in your DNA, then > complex I will be normal---like a cake recipe that turns out right. If there > is a mistake in the recipe, the proteins in complex I may be missing or > damaged--and the cake falls flat. > > That means there are two ways to diagnose a mitochondrial disease like > complex I deficiency. > > 1. You can look for the mistake in the recipe---the disease-causing > mutation--the " mis-spelled " part of the genetic code that contains the > instructions for complex I. > > 2. Or you can look at the fallen cake, measure the biochemical ingredients > of the cake and figure out which protein is damaged or missing. > > Given our current technology, we are better at #2 than #1. Most often #2 is > the best bet for diagnosis. In this case, the " fallen cake " is muscle. So > they take a piece of muscle and measure it biochemically (using enzyme > assays) to see if complex I is present in normal amounts. If not, that > confirms the diagnosis. > > But scientists being of a scientific mind, they like to get to the bottom of > the story. The bottom of the story in genetic disease is in the DNA. > > There are many different kinds of " mis-spellings " in the genetic code for > complex I that can cause complex I to be damaged or missing. These mutations > or changes are given individual names---strings of letters and numbers that > make a sort of " address " which identifies where the mutation is in the DNA > and what kind of " mis-spelling " occurred at that location. > > Because there are so many different kinds of mutations or " mis- spellings " > just for complex I, many have not been identified yet. So your chances of > getting a diagnosis by looking at the recipe are slim, at least for now. The > science just isn't there yet. Still, it can be worth checking. > > Best bet is looking at the fallen cake and identifying which biochemical > ingredient is missing, which is the way most people in this group have > gotten a diagnosis. > > This analogy greatly simplifies everything, of course, but was the best > thing I could think of at the moment. > > Barbara Quote Link to comment Share on other sites More sharing options...
Guest guest Posted September 8, 2005 Report Share Posted September 8, 2005 Here's another question for you, RH. Maybe with your background in biochemistry you can clear this up for me. I once referred to complex I as a group of enzymes and Dr. Vladutiu corrected me and said it was one enzyme. This I understand now, but what I don't understand is why one enzyme is referred to as a " complex " in this case. Yes, it has many subunits, but so do many other enzymes. CPT, for example, has four subunits and it is never referred to as a " complex, " only an individual enzyme. Biochemically, what qualifies the work of one enzyme to earn the distinguished label " complex " ? Is it literally the " complexity " of biochemical steps that is being recognized? All enzymes in any metabolic cycle work in clearly defined biochemical sequences similar to the five black boxes of OXPHOS---like the cars of a train. So that part isn't different, as far as I can see. Obviously not a burning question that keeps me awake at night, but something I've wondered about for years. :-) http://www.bmb.leeds.ac.uk/illingworth/oxphos/complex1.htm B > Re: athena mito results > > To add to this, my understanding is that not all mitochondrial > proteins (of which Complex I is one, or rather Complex I is a protein > complex, more than one protein I think) are coded 100% from mtDNA > (mitochondrial DNA), there is often a nDNA (nuclear DNA) component as > well. > > Perhaps think of it, taking Barbara's analogy, as making a cake, but > the cake recipe is in one book and the frosting recipe in the other > book, and instructions for decorations somewhere else (i don't know, > candied violets maybe?). Even the sequencing, which individually > checks one's DNA versus a normal DNA, is limited because they just > may not know where all the parts of the complex " come from " . Genetic > blood testing takes one little bit of DNA and sees if one particular > mutation is present. > > I have some " misspellings " in my mtDNA, but none that lead to a > genetic disorder ( " normal " defects if you can imagine that). But I > don't think they sequenced the nDNA portion, which is the part they > suspect is messed up for me, because of the time and trouble and > possibly lack of knowledge of it. > > The test that was very abnormal for me was one where they essentially > check if Complex I can do its normal biochemical reaction. Mine > couldn't. As far as how I can function with no activity (and > function pretty well), the interpretation is that their test is > limited in scope and doesn't put in all possible raw materials for > the biochemical reaction, just a standard one that they have results > for normal and affected people for. > > So another analogy is that the complexes are each little black boxes > where you throw in a raw material, and get a product out, but they > are in a line so any part could be not working to cause a problem. > My first little black box didn't know what to do with the raw > material given when they tested it (others please correct me if this > is incorrect). > > Never be afraid to ask a question, the only stupid question is the > one not asked... > > Take care, > RH Quote Link to comment Share on other sites More sharing options...
Guest guest Posted September 8, 2005 Report Share Posted September 8, 2005 http://www.athenadiagnostics.com/site/product_search/test_description_t emplate.asp?id=208 Here's a link to the Athena description of a mitochondrail myopathy mtDNA evaluation. Kim > Hi Kim > I would like to know what the full panel involves, can you explain or point me to a place where it is described? > Thanks, Lene > > > > From: " klaga5 " > Subject: Re: athena mito results > > Did they only test for melas or did they do the full mito panel? > (mine was the full panel) > Kim Quote Link to comment Share on other sites More sharing options...
Guest guest Posted September 8, 2005 Report Share Posted September 8, 2005 That makes sense. I wish I had known that before the costly DNA test. What a waste. Kim > > I still don't really understand it I guess. Complex I doesn't show > > up on genetic tests? Sorry if that's a dumb question. > > Kim > > Not a dumb question at all. > > Think of your DNA as a blueprint or recipe for building proteins. If the > recipe for the proteins in complex I are written correctly in your DNA, then > complex I will be normal---like a cake recipe that turns out right. If there > is a mistake in the recipe, the proteins in complex I may be missing or > damaged--and the cake falls flat. > > That means there are two ways to diagnose a mitochondrial disease like > complex I deficiency. > > 1. You can look for the mistake in the recipe---the disease-causing > mutation--the " mis-spelled " part of the genetic code that contains the > instructions for complex I. > > 2. Or you can look at the fallen cake, measure the biochemical ingredients > of the cake and figure out which protein is damaged or missing. > > Given our current technology, we are better at #2 than #1. Most often #2 is > the best bet for diagnosis. In this case, the " fallen cake " is muscle. So > they take a piece of muscle and measure it biochemically (using enzyme > assays) to see if complex I is present in normal amounts. If not, that > confirms the diagnosis. > > But scientists being of a scientific mind, they like to get to the bottom of > the story. The bottom of the story in genetic disease is in the DNA. > > There are many different kinds of " mis-spellings " in the genetic code for > complex I that can cause complex I to be damaged or missing. These mutations > or changes are given individual names---strings of letters and numbers that > make a sort of " address " which identifies where the mutation is in the DNA > and what kind of " mis-spelling " occurred at that location. > > Because there are so many different kinds of mutations or " mis- spellings " > just for complex I, many have not been identified yet. So your chances of > getting a diagnosis by looking at the recipe are slim, at least for now. The > science just isn't there yet. Still, it can be worth checking. > > Best bet is looking at the fallen cake and identifying which biochemical > ingredient is missing, which is the way most people in this group have > gotten a diagnosis. > > This analogy greatly simplifies everything, of course, but was the best > thing I could think of at the moment. > > Barbara Quote Link to comment Share on other sites More sharing options...
Guest guest Posted September 8, 2005 Report Share Posted September 8, 2005 I think I'll wait. Atlanta has been calling me every couple weeks waiting on the test results to schedule my appointment. I know they can get me an appointment in the next couple months, then we'll go from there. Kim > > My primary doc doesn't want to give me anything without a > diagnosis. > > My MDA doc is out of ideas. I'll just have to find a way to get to > > Atlanta. I'm thankful they're willing to see me. > > Kim > > > > > If you think you " could " have > > > mito, you might want to talk to a doctor about starting some > > > supplements to see if you have improvement. > > > > > > Take care, > > > RH Quote Link to comment Share on other sites More sharing options...
Guest guest Posted September 8, 2005 Report Share Posted September 8, 2005 Thank you Ann, It's only been three years of testing, since my heart valve was replaced. I guees I feel like it's been a lifetime. I've never felt well, and it was blamed on my heart, but the cardiologist, and heart surgeon didn't think it all fit. Now I know it didn't, but still don't know the whole answer. At least I know it's muscles now. That's one step closer to a diagnosis. Kim > > The other abnormalities you mentioned on your biopsy may lead to a > diagnosis > > also. I hope they go ahead and do electron microscopy studies and > follow > > those leads. > > > > I sure wish there was some way to shorten the agony of getting a > diagnosis, > > but I'm afraid it is often like this. Just don't give up. There is > an > > answer! > > > > Hugs, > > Barbara > > > > > Re: athena mito results > > > > > > Barbara, > > > Of course I would have prefered that it was a definative test > > > result, but I want the truth. I guess I'd better accept I'll > need > > > to go to Atlanta. At least it'll probably represent the end of > > > testing. Hopefully it'll mean a diagnosis too. > > > Thanks for the info. > > > Kim > > > > > > > > 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...
Guest guest Posted September 8, 2005 Report Share Posted September 8, 2005 Kim Genetic testing is done on frozen tissue, so it can be sent to Dr. Shoffner. This is what Cleveland Clinic does. Arrangments have to be made with Horizen Labs before it is sent and insurance pre-approval is needed. It is very expensive. laurie > I think I'll wait. Atlanta has been calling me every couple weeks > waiting on the test results to schedule my appointment. I know they > can get me an appointment in the next couple months, then we'll go > from there. > Kim > > > > > My primary doc doesn't want to give me anything without a > > diagnosis. > > > My MDA doc is out of ideas. I'll just have to find a way to get > to > > > Atlanta. I'm thankful they're willing to see me. > > > Kim > > > > > > > If you think you " could " have > > > > mito, you might want to talk to a doctor about starting some > > > > supplements to see if you have improvement. > > > > > > > > Take care, > > > > RH > > > > > > 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...
Guest guest Posted September 8, 2005 Report Share Posted September 8, 2005 I'm not sure why the whole link didn't work. If you copy the last part that isn't pink, click on what's there, then paste the last bit onto the rest of the link, it'll take you there. Kim > > Hi Kim > > I would like to know what the full panel involves, can you explain > or point me to a place where it is described? > > Thanks, Lene > > > > > > > > From: " klaga5 " > > Subject: Re: athena mito results > > > > Did they only test for melas or did they do the full mito panel? > > (mine was the full panel) > > Kim Quote Link to comment Share on other sites More sharing options...
Guest guest Posted September 8, 2005 Report Share Posted September 8, 2005 genetic tests can be done on blood or muscle. Mine was done on blood. Kim > > > > My primary doc doesn't want to give me anything without a > > > diagnosis. > > > > My MDA doc is out of ideas. I'll just have to find a way to get > > to > > > > Atlanta. I'm thankful they're willing to see me. > > > > Kim > > > > > > > > > If you think you " could " have > > > > > mito, you might want to talk to a doctor about starting some > > > > > supplements to see if you have improvement. > > > > > > > > > > Take care, > > > > > RH > > > > > > > > > > > > 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...
Guest guest Posted September 9, 2005 Report Share Posted September 9, 2005 Hi Barbara - just wanted to say thankyou to you all including RH and Laurie who go to the trouble of getting into detail and explaining things in such detail (are you all scientists?) It is all very interesting. Pamela (just diagnosed within 3 mths, with mito (from muscle biopsy), melas A3243G (from urine cells) - " lucky " I guess to get such a quick dx)) RE: athena mito results > I still don't really understand it I guess. Complex I doesn't show > up on genetic tests? Sorry if that's a dumb question. > Kim Not a dumb question at all. Think of your DNA as a blueprint or recipe for building proteins. If the recipe for the proteins in complex I are written correctly in your DNA, then complex I will be normal---like a cake recipe that turns out right. If there is a mistake in the recipe, the proteins in complex I may be missing or damaged--and the cake falls flat. That means there are two ways to diagnose a mitochondrial disease like complex I deficiency. 1. You can look for the mistake in the recipe---the disease-causing mutation--the " mis-spelled " part of the genetic code that contains the instructions for complex I. 2. Or you can look at the fallen cake, measure the biochemical ingredients of the cake and figure out which protein is damaged or missing. Given our current technology, we are better at #2 than #1. Most often #2 is the best bet for diagnosis. In this case, the " fallen cake " is muscle. So they take a piece of muscle and measure it biochemically (using enzyme assays) to see if complex I is present in normal amounts. If not, that confirms the diagnosis. But scientists being of a scientific mind, they like to get to the bottom of the story. The bottom of the story in genetic disease is in the DNA. There are many different kinds of " mis-spellings " in the genetic code for complex I that can cause complex I to be damaged or missing. These mutations or changes are given individual names---strings of letters and numbers that make a sort of " address " which identifies where the mutation is in the DNA and what kind of " mis-spelling " occurred at that location. Because there are so many different kinds of mutations or " mis-spellings " just for complex I, many have not been identified yet. So your chances of getting a diagnosis by looking at the recipe are slim, at least for now. The science just isn't there yet. Still, it can be worth checking. Best bet is looking at the fallen cake and identifying which biochemical ingredient is missing, which is the way most people in this group have gotten a diagnosis. This analogy greatly simplifies everything, of course, but was the best thing I could think of at the moment. Barbara 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...
Guest guest Posted September 9, 2005 Report Share Posted September 9, 2005 Pamela You are welcome. I'm not a scientist - just a patient who has been doing this for lots of years. I do have some basic medical background. My degree is in teaching the physically and health impaired. I wish I had had more biochemistry, so I could understand more. laurie > Hi Barbara - just wanted to say thankyou to you all including RH and Laurie who go to the trouble of getting into detail and explaining things in such detail (are you all scientists?) It is all very interesting. Pamela (just diagnosed within 3 mths, with mito (from muscle biopsy), melas A3243G (from urine cells) - " lucky " I guess to get such a quick dx)) > RE: athena mito results > > > > I still don't really understand it I guess. Complex I doesn't show > > up on genetic tests? Sorry if that's a dumb question. > > Kim > > Not a dumb question at all. > > Think of your DNA as a blueprint or recipe for building proteins. If the > recipe for the proteins in complex I are written correctly in your DNA, then > complex I will be normal---like a cake recipe that turns out right. If there > is a mistake in the recipe, the proteins in complex I may be missing or > damaged--and the cake falls flat. > > That means there are two ways to diagnose a mitochondrial disease like > complex I deficiency. > > 1. You can look for the mistake in the recipe---the disease-causing > mutation--the " mis-spelled " part of the genetic code that contains the > instructions for complex I. > > 2. Or you can look at the fallen cake, measure the biochemical ingredients > of the cake and figure out which protein is damaged or missing. > > Given our current technology, we are better at #2 than #1. Most often #2 is > the best bet for diagnosis. In this case, the " fallen cake " is muscle. So > they take a piece of muscle and measure it biochemically (using enzyme > assays) to see if complex I is present in normal amounts. If not, that > confirms the diagnosis. > > But scientists being of a scientific mind, they like to get to the bottom of > the story. The bottom of the story in genetic disease is in the DNA. > > There are many different kinds of " mis-spellings " in the genetic code for > complex I that can cause complex I to be damaged or missing. These mutations > or changes are given individual names---strings of letters and numbers that > make a sort of " address " which identifies where the mutation is in the DNA > and what kind of " mis-spelling " occurred at that location. > > Because there are so many different kinds of mutations or " mis-spellings " > just for complex I, many have not been identified yet. So your chances of > getting a diagnosis by looking at the recipe are slim, at least for now. The > science just isn't there yet. Still, it can be worth checking. > > Best bet is looking at the fallen cake and identifying which biochemical > ingredient is missing, which is the way most people in this group have > gotten a diagnosis. > > This analogy greatly simplifies everything, of course, but was the best > thing I could think of at the moment. > > Barbara > > > > > 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...
Guest guest Posted September 9, 2005 Report Share Posted September 9, 2005 Hi Pamela, I'm not a scientist either, but I have worked as a medical journalist and also had a lot of contact with mito researchers. Like Laurie, I'm a long-time patient, initial diagnosis 1983. Glad you were able to get a diagnosis so quickly. That is very encouraging to hear. Barbara > Re: athena mito results > > Pamela > > You are welcome. > > I'm not a scientist - just a patient who has been doing this for lots > of years. I do have some basic medical background. My degree is in > teaching the physically and health impaired. I wish I had had more > biochemistry, so I could understand more. > > laurie > > > > Hi Barbara - just wanted to say thankyou to you all including RH and Laurie who > go to the trouble of getting into detail and explaining things in such detail (are you > all scientists?) It is all very interesting. Pamela (just diagnosed within 3 mths, with > mito (from muscle biopsy), melas A3243G (from urine cells) - " lucky " I guess to get > such a quick dx)) > > RE: athena mito results > > > > > > > I still don't really understand it I guess. Complex I doesn't show > > > up on genetic tests? Sorry if that's a dumb question. > > > Kim > > > > Not a dumb question at all. > > > > Think of your DNA as a blueprint or recipe for building proteins. If the > > recipe for the proteins in complex I are written correctly in your DNA, then > > complex I will be normal---like a cake recipe that turns out right. If there > > is a mistake in the recipe, the proteins in complex I may be missing or > > damaged--and the cake falls flat. > > > > That means there are two ways to diagnose a mitochondrial disease like > > complex I deficiency. > > > > 1. You can look for the mistake in the recipe---the disease-causing > > mutation--the " mis-spelled " part of the genetic code that contains the > > instructions for complex I. > > > > 2. Or you can look at the fallen cake, measure the biochemical ingredients > > of the cake and figure out which protein is damaged or missing. > > > > Given our current technology, we are better at #2 than #1. Most often #2 is > > the best bet for diagnosis. In this case, the " fallen cake " is muscle. So > > they take a piece of muscle and measure it biochemically (using enzyme > > assays) to see if complex I is present in normal amounts. If not, that > > confirms the diagnosis. > > > > But scientists being of a scientific mind, they like to get to the bottom of > > the story. The bottom of the story in genetic disease is in the DNA. > > > > There are many different kinds of " mis-spellings " in the genetic code for > > complex I that can cause complex I to be damaged or missing. These mutations > > or changes are given individual names---strings of letters and numbers that > > make a sort of " address " which identifies where the mutation is in the DNA > > and what kind of " mis-spelling " occurred at that location. > > > > Because there are so many different kinds of mutations or " mis-spellings " > > just for complex I, many have not been identified yet. So your chances of > > getting a diagnosis by looking at the recipe are slim, at least for now. The > > science just isn't there yet. Still, it can be worth checking. > > > > Best bet is looking at the fallen cake and identifying which biochemical > > ingredient is missing, which is the way most people in this group have > > gotten a diagnosis. > > > > This analogy greatly simplifies everything, of course, but was the best > > thing I could think of at the moment. > > > > Barbara > > > > > > > > > > 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...
Guest guest Posted September 9, 2005 Report Share Posted September 9, 2005 Here's a definition for you: http://www.answers.com/topic/protein-complex I think the short answer is that an enzyme can be a single protein or a protein complex. We were originally taught that " an enzyme is a protein that catalyzes a reaction " , but now I suppose it's " an enzyme is a protein or protein complex that catalyzes a reaction " . An interesting other point I read was that there are cohesive and dynamic protein complexes. Cohesive protein complexes have only proteins that are unique to that protein complex. Dynamic protein complexes have one or more proteins that are not unique to the complex, that is they occur in other protein complexes too. This site is *very* interesting, and note that Complex I is coded from both nDNA and mtDNA (I am thought to have a defect in the nDNA genetic code of Complex I, not the mtDNA). http://www.mitosciences.com/complex_i.html Some enzymes are able to catalyze reactions with just a single protein, perhaps made up of two, four, or eight subunits, but only a single protein nonetheless. That certainly isn't the case with Complex I, but is the case for CPT as I understand it. The molecular weights for the two are 950,000 for Complex I, and CPT is just under 90,000. CPT is coded from one gene location: http://www.genecards.org/cgi-bin/carddisp?CPT1B http://us.expasy.org/cgi-bin/sprot-search-de?cpt%20human and Complex I is not. http://us.expasy.org/cgi-bin/sprot-search-de?nadh%20human Hope that helps, RH > Here's another question for you, RH. Maybe with your background in > biochemistry you can clear this up for me. > > I once referred to complex I as a group of enzymes and Dr. Vladutiu > corrected me and said it was one enzyme. This I understand now, but what I > don't understand is why one enzyme is referred to as a " complex " in this > case. Yes, it has many subunits, but so do many other enzymes. CPT, for > example, has four subunits and it is never referred to as a " complex, " only > an individual enzyme. Biochemically, what qualifies the work of one enzyme > to earn the distinguished label " complex " ? Is it literally the " complexity " > of biochemical steps that is being recognized? All enzymes in any metabolic > cycle work in clearly defined biochemical sequences similar to the five > black boxes of OXPHOS---like the cars of a train. So that part isn't > different, as far as I can see. > > Obviously not a burning question that keeps me awake at night, but something > I've wondered about for years. :-) > > http://www.bmb.leeds.ac.uk/illingworth/oxphos/complex1.htm > > B > > > Re: athena mito results > > > > To add to this, my understanding is that not all mitochondrial > > proteins (of which Complex I is one, or rather Complex I is a protein > > complex, more than one protein I think) are coded 100% from mtDNA > > (mitochondrial DNA), there is often a nDNA (nuclear DNA) component as > > well. > > > > Perhaps think of it, taking Barbara's analogy, as making a cake, but > > the cake recipe is in one book and the frosting recipe in the other > > book, and instructions for decorations somewhere else (i don't know, > > candied violets maybe?). Even the sequencing, which individually > > checks one's DNA versus a normal DNA, is limited because they just > > may not know where all the parts of the complex " come from " . Genetic > > blood testing takes one little bit of DNA and sees if one particular > > mutation is present. > > > > I have some " misspellings " in my mtDNA, but none that lead to a > > genetic disorder ( " normal " defects if you can imagine that). But I > > don't think they sequenced the nDNA portion, which is the part they > > suspect is messed up for me, because of the time and trouble and > > possibly lack of knowledge of it. > > > > The test that was very abnormal for me was one where they essentially > > check if Complex I can do its normal biochemical reaction. Mine > > couldn't. As far as how I can function with no activity (and > > function pretty well), the interpretation is that their test is > > limited in scope and doesn't put in all possible raw materials for > > the biochemical reaction, just a standard one that they have results > > for normal and affected people for. > > > > So another analogy is that the complexes are each little black boxes > > where you throw in a raw material, and get a product out, but they > > are in a line so any part could be not working to cause a problem. > > My first little black box didn't know what to do with the raw > > material given when they tested it (others please correct me if this > > is incorrect). > > > > Never be afraid to ask a question, the only stupid question is the > > one not asked... > > > > Take care, > > RH Quote Link to comment Share on other sites More sharing options...
Guest guest Posted September 9, 2005 Report Share Posted September 9, 2005 It's easy to say it is a waste since nothing was found, but there's really not much for them to work with unless you get a muscle biopsy, and then it seems a " fresh muscle biopsy " like done in Atlanta has worked for some people who had negative muscle biopsies elsewhere. The mito blood tests are kind of " is it or isn't it " for specific defects as far as I can tell. The fresh muscle biopsy was about $20K from my recollection, as I mentioned before I got it covered as in-network because there were no in-network doctors who could do the muscle testing. Take care, RH > > > I still don't really understand it I guess. Complex I doesn't > show > > > up on genetic tests? Sorry if that's a dumb question. > > > Kim > > > > Not a dumb question at all. > > > > Think of your DNA as a blueprint or recipe for building proteins. > If the > > recipe for the proteins in complex I are written correctly in your > DNA, then > > complex I will be normal---like a cake recipe that turns out > right. If there > > is a mistake in the recipe, the proteins in complex I may be > missing or > > damaged--and the cake falls flat. > > > > That means there are two ways to diagnose a mitochondrial disease > like > > complex I deficiency. > > > > 1. You can look for the mistake in the recipe---the disease- causing > > mutation--the " mis-spelled " part of the genetic code that contains > the > > instructions for complex I. > > > > 2. Or you can look at the fallen cake, measure the biochemical > ingredients > > of the cake and figure out which protein is damaged or missing. > > > > Given our current technology, we are better at #2 than #1. Most > often #2 is > > the best bet for diagnosis. In this case, the " fallen cake " is > muscle. So > > they take a piece of muscle and measure it biochemically (using > enzyme > > assays) to see if complex I is present in normal amounts. If not, > that > > confirms the diagnosis. > > > > But scientists being of a scientific mind, they like to get to the > bottom of > > the story. The bottom of the story in genetic disease is in the > DNA. > > > > There are many different kinds of " mis-spellings " in the genetic > code for > > complex I that can cause complex I to be damaged or missing. These > mutations > > or changes are given individual names---strings of letters and > numbers that > > make a sort of " address " which identifies where the mutation is in > the DNA > > and what kind of " mis-spelling " occurred at that location. > > > > Because there are so many different kinds of mutations or " mis- > spellings " > > just for complex I, many have not been identified yet. So your > chances of > > getting a diagnosis by looking at the recipe are slim, at least > for now. The > > science just isn't there yet. Still, it can be worth checking. > > > > Best bet is looking at the fallen cake and identifying which > biochemical > > ingredient is missing, which is the way most people in this group > have > > gotten a diagnosis. > > > > This analogy greatly simplifies everything, of course, but was the > best > > thing I could think of at the moment. > > > > Barbara Quote Link to comment Share on other sites More sharing options...
Guest guest Posted September 9, 2005 Report Share Posted September 9, 2005 My understanding is that they can't do complete genetic testing on blood - they have to have a known defect to test against. Testing on blood is therefore very limited, by the specific identified genetic defects of which there are relatively few. On the other hand, I think several (more than that?) of us have benefited from having the lactate and pyruvate levels tested in our blood, a biochemical not genetic test. I'm not sure if it is specific to mito, but it is indicative of a problem in the mitochondria. Take care, RH > > > > > My primary doc doesn't want to give me anything without a > > > > diagnosis. > > > > > My MDA doc is out of ideas. I'll just have to find a way to > get > > > to > > > > > Atlanta. I'm thankful they're willing to see me. > > > > > Kim > > > > > > > > > > > If you think you " could " have > > > > > > mito, you might want to talk to a doctor about starting > some > > > > > > supplements to see if you have improvement. > > > > > > > > > > > > Take care, > > > > > > RH > > > > > > > > > > > > > > > > > > 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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