finger and toe nails

[faith]

Kim,

Could you give us just a little wrap up in your own words of what this all points to, I mean what lead you to look at these things and did what you find boost a certain theory of sorts? Have you concluded anything?

 

btw, I think my son's nails are just normal, but I can pretty much still peel them when he needs trimming, like you can when they are babies, don't really have to use a clipper. Hair is thick and wavy. ..... Are you trying to connect a deficiency of cystein?

 

And re the methionine synthesis--what should happen after that? cysteine?

 

 

 

Thanks

Faith

[Sunshine]

Kim,

 

Interesting thread... I'm not sure I totally understand the new link (re the golgi stuff). But, a few things did jump out at me. I'll throw them out there, but remember it's the end of a long, brutal work week for me, and it's past my bedtime. (Not that I make great sense when not under such compromised conditions but...).

 

The first thing is that we have Osteo in spades on both sides of the family. Would that affect gluconic acid levels???

 

The other thing that I picked up on is this:

 

" In aqueous solution at neutral pH, carboxylic acid forms the gluconate ion and the

salts of gluconic acid are also known as gluconates. "

 

Dr. Amy's forum has quite a bit of discussion with regards to pH. What I have learned from there is that typically the bad gut bugs thrive in an acidic environment and good flora dies in it. Elevated gut pH has also been associated with clostridia. And, if the stomach pH is too high, then there is not enough acid to stimulate the hormones that in turn stimulate enzyme production. Perhaps many of our chicklets have an imbalanced pH which also affects the level of gluconic acid.

 

Here is a quote from Dr. Amy, which talks about pH and magnesium...it's quite interesting!! The website is underneath for anyone who is interested in the article.

"It is interesting to note that nutrient status can be impacted by an acid-base balance in the body. Researchers in Germany found that "acid-base status affects renal magnesium losses, irrespectively of magnesium intake." This means that besides not eating enough foods high in magnesium, an acid load in the body could be another factor that contributes to a magnesium deficiency condition."

 

http://www.ch3nutrigenomics.com/phpBB2/vie...ae5a7b0bc334366

 

Just wondering, Kim, if this ties in with your thoughts, or am I in left field picking the daisies???

 

Sunshine

[kim]

nursepatty

 

If you read the articles about supplementing sulfur in the form of MSM, it says people that that have problems with sulfa drugs don't have problems with MSM, but I sure wouldn't buy that until I really did some digging. Are these drug allergies the liver's inability to detox a certain substance in the drug, what is the difference btwn sulfa sulfur sulfate? I guess once again, if you ask the "why" questions, you might find answers to other questions as well. I haven't looked at it, but if you do please let us know what you find.

 

Faith,

 

Without going back and looking at MTHFR (so always confirm on your own), I think the idea is that you are not making it to methionine. If you don't have methionine you don't make gluathione properly because of the problem with B12. Glutathione is about the most important antioxidant in our bodies. Not enough glut, improper detox. The CBS mutation is the one where homocystein is not converting to cystein.

 

If you're looking at sulfur deficiency, Waring's article says you need methionine and cystein to get sulfur. Well, we (my boys) may have enough of all of these, but maybe not the enzyme that gets it out of the cell in the glucosaminoglycan chains. So, as Peglem said, you can have different problems along a pathway, with the same end result. You have to figure out where the problem is. Faith, I don't think one "bad" copy of the MTHFR gene is the whole answer either but I sure respect what I have read on the Yasko forum. It's all just such a big picture with different pieces for everyone, so it's really impossible for me to answer what your asking. I'm just doing the best I can to try connect some dots. It may not apply to anyone on this forum, or there could be peices that are important to many but the bottom line, you either have to pay one of the best, or spend hours and hours using every clue in your particular situation and READING some tough stuff.

 

Boy Faith, posting this to you, just turned on a big old light bulb for me. Thanks Faith, you're a genious!!!!!!!! Keep asking those questions of yours!

 

 

Sunshine,

 

I will get back to you! One thing thou, when you said osteo in spades I'm assuming that you meant osteoarthritis?

 

 

Michelle and Myrose If you're reading, I hope you guys will contribute to anything that rings a bell for you too.

[kim]

response to others posted above

 

CP,

 

Seems we have something in common here. Why such exteme low values. Did your Dr. comment on that? I think they commonly look at that as a marker for "bad" bacteria but I think something else might be up with this. I was actually looking at lactic acid and it got me thinking about a dysbiosis profile that youngest had quite a while ago.

 

Here are a couple of things that made me wonder. Remember, I'm looking for things that indicate low gluconic acid. don't know how the phenyl part plays in. Lot's of reading to do on this. Our hippurate was way low too, but I think that is because he eats so little protein. Did your son have anything to indicate high ammonia?

 

 

http://jn.nutrition.org/cgi/content/abstract/132/8/2229

 

Gluconic acid reaches the large intestine to stimulate lactic acid bacteria. However, the fermentation pattern of gluconic acid has yet to be elucidated. Accordingly, we examined the fermentation properties induced by gluconic acid in the pig cecal digesta in vitro. We also tested sorbitol and glucose, substrates for which the fermentation rate and patterns are known. The gluconic acid–utilizing bacteria were further isolated from pig cecal digesta and identified to examine the effect of gluconic acid on hind gut fermentation. Gluconic acid was fermented more slowly than were the other two substrates. Gluconic acid stimulated butyrate production; the butyrate molar percentage reached 26%, which is considered a high butyrate production. The majority of gluconic acid fermenters were identified as lactic acid bacteria, such as Lactobacillus reuteri and L. mucosae, and acid-utilizing bacteria, such as Megasphaera elsdenii and Mitsuokella multiacida. The gluconic acid fermented by lactic acid bacteria, and the lactate and acetate that were produced were used to form butyrate by acid-utilizing bacteria, such as M. elsdenii. Gluconic acid may be useful as a prebiotic to stimulate butyrate production in the large intestine.

 

 

http://en.wikipedia.org/wiki/Butyric_acid

 

Butyric acid has been associated with the ability to inhibit the function of histone deacetylase enzymes, thereby favouring an acetylated state of histones in the cell. Acetylated histones have a lower affinity for DNA than non-acetylated histones, due to the neutralisation of electrostatic charge interactions. In general, it is thought that transcription factors will be unable to access regions where histones are tightly associated with DNA (ie non-acetylated, e.g., heterochromatin). Therefore, it is thought that butyric acid enhances the transcriptional activity at promoters, which are typically silenced/downregulated due to histone deacetylase activity.

[CSP]

Good morning Kim,

 

The only comment she made was he was low in good and bad bacteria. She wanted to know if he had been on antibiotics. I said, if he had it was when he was a baby, he had thrush. Other then that, never. She seemed puzzled that both would be low.

 

If I'm reading this right relating to the ammonia was his Energy markers high in both Cis-Aconitate and Isocitrate.

 

C.P.

[peglem]

Good morning Kim,

 

The only comment she made was he was low in good and bad bacteria. She wanted to know if he had been on antibiotics. I said, if he had it was when he was a baby, he had thrush. Other then that, never. She seemed puzzled that both would be low.

 

If I'm reading this right relating to the ammonia was his Energy markers high in both Cis-Aconitate and Isocitrate.

 

C.P.

 

I almost hate to mention this, because it means yet another direction for research, but its possible the low values for yeast and bacteria are because of the formation of biofilms. This is when bacteria and (sometimes w/yeast) form a community, almost like an organism. When this happens, a coating is formed over the community which is fairly impenetable and allows the colony to hide from the body and from most antibiotics. Most antibiotics do not kill the organisms protected by the biofilm, only the "satellite organisms" sent out from it. The only antibiotic that has been shown to penetrate this protective film is...drumroll please.....zithromax!

[michele]

These are interesting findings. I am also allergic to sulfa drugs and break out in hives, throat swells, swell up etc. I really liked the part about the biofilms and the zithromax. Is there more research information on the benefits of zithromax? I have never been successful in getting it long term for my boy. Do other parents have intolerances to sulfa?

 

Michele

nursepatty

 

If you read the articles about supplementing sulfur in the form of MSM, it says people that that have problems with sulfa drugs don't have problems with MSM, but I sure wouldn't buy that until I really did some digging. Are these drug allergies the liver's inability to detox a certain substance in the drug, what is the difference btwn sulfa sulfur sulfate? I guess once again, if you ask the "why" questions, you might find answers to other questions as well. I haven't looked at it, but if you do please let us know what you find.

 

Faith,

 

Without going back and looking at MTHFR (so always confirm on your own), I think the idea is that you are not making it to methionine. If you don't have methionine you don't make gluathione properly because of the problem with B12. Glutathione is about the most important antioxidant in our bodies. Not enough glut, improper detox. The CBS mutation is the one where homocystein is not converting to cystein.

 

If you're looking at sulfur deficiency, Waring's article says you need methionine and cystein to get sulfur. Well, we (my boys) may have enough of all of these, but maybe not the enzyme that gets it out of the cell in the glucosaminoglycan chains. So, as Peglem said, you can have different problems along a pathway, with the same end result. You have to figure out where the problem is. Faith, I don't think one "bad" copy of the MTHFR gene is the whole answer either but I sure respect what I have read on the Yasko forum. It's all just such a big picture with different pieces for everyone, so it's really impossible for me to answer what your asking. I'm just doing the best I can to try connect some dots. It may not apply to anyone on this forum, or there could be peices that are important to many but the bottom line, you either have to pay one of the best, or spend hours and hours using every clue in your particular situation and READING some tough stuff.

 

Boy Faith, posting this to you, just turned on a big old light bulb for me. Thanks Faith, you're a genious!!!!!!!! Keep asking those questions of yours!

 

 

Sunshine,

 

I will get back to you! One thing thou, when you said osteo in spades I'm assuming that you meant osteoarthritis?

 

 

Michelle and Myrose If you're reading, I hope you guys will contribute to anything that rings a bell for you too.

[kim]

Could you give us just a little wrap up in your own words of what this all points to, I mean what lead you to look at these things and did what you find boost a certain theory of sorts? Have you concluded anything?

 

Faith,

 

When trying to figure out how to answer that question, it occured to me that I needed to go back and look at people that had the multiple hereditary syndrome. I was making an assumption that my boys sort of developed this, not necessarly born with it. I was perfectly willing to accept that it was just an inherited condition, but I was mostly looking at current research. When I did that (went back and looked at the hereditary symdrome), it hit me that my boys most likely DO NOT have that disorder. I should have been focusing on Sunshine's info. The CBS mutation.

 

Sunshine, if you're reading, could you PM your Dr.s phone #. I would very much like to speak with her and make arrangements for testing for at least one of the boys. I can probably find it, but if you have it handy, I would really appreciate it.

 

I left this thread hang, as I was trying to digest how foolish it was to jump to what was very likely the wrong conclusion. Sunshine, I think for now we can forget the problem that occurs in the golgi. I do think the study that I have been referring to provides very useful info though.

 

I'm typing on the way out the door, but I appreciate SO much the discussion on this thread.

 

I'll be back and will try to give more info to some of the remarks here.

 

Thank you all again!

[kim]

CP

 

Yes, we have that under COMPOUNDS OF BACTERIAL OR YEAST/FUNGAL ORIGIN.

 

Son was very very low for both.

 

Only thing high in that compound was Hippurate. (Part of his failing to digest protein)

 

CP

 

Does it look like having a CBS mutation would result LOW forms of at least some forms of yeast. I'm thinking that the low readings in the Phenylpropinonate and phenylacetate are due to low gluconic acid (?) but this looks interesting too. Did your sons testing reflect B12 or folate?

 

http://www.ncbi.nlm.nih.gov/pubmed/1754059...Pubmed_RVDocSum

 

Missense mutations in the cystathionine beta-synthase (CBS) gene, such as I278T, are responsible for CBS deficiency, the most common inherited disorder in sulfur metabolism.

 

and

 

Expression of human mutant CBS proteins in Saccharomyces cerevisiae reveals that most disease causing mutations severely inhibit enzyme activity and cannot support growth of yeast on cysteine-free media.

 

Here is another article on CBS

 

http://www.ncbi.nlm.nih.gov/pubmed/1768664...Pubmed_RVDocSum

 

Increased homocysteine concentrations in CBS gene mutation carriers are associated with reduced concentrations of folic acid and vitamin B12 in blood. In view of the adverse effects of mild hyperhomocysteinemia, routine testing of vitamin status in parents of homocystinuria patients may be warranted. The causal relationship and pathophysiological consequences are uncertain; it is likely that CBS gene mutation carriers need higher doses of dietary vitamins.

[kim]

Faith,

 

I think I'm finally understanding the MTHFR/CBS a little better.

 

It looks to me like a MTHFR mutation would result in inadequate methione which would throw off the CBS cycle without having a mutation in CBS. If methionine isn't there, you aren't going to make it to sulfate. Can someone else look at this diagram and see if that's what they get out of it? I think that's why these two things are discussed together in a lot of articles. I think about the mom who posted recently about lack of ability to utilize B12. Her child develops tics.....no one is looking for these things??????? In that situation, it may not be a mthfr or cbs mutation, but again, you need these pathways to function right no matter where in the chain the glitch is.

 

I'm not sure how the therma variant fits into this. Would that pathway only be affected during an increase in body temp? Did your Dr. that tested for the MTHFR mutation explain any of it to you?

 

http://circ.ahajournals.org/cgi/reprint/99/1/178.pdf

[faith]

Kim,

okay, yes, I think what you get is correct, the methionine is needed to be made there, and with our inability to convert the b12 and folic acid, then the methionine (I think) gets stuck and too much homocysteine is built up and not converted to methionine or whatever other pathway it is supposed to be a donor for. BUT, here is my problem and frustration with this -- WE ARE doing the methy12 shots and folinic acid, so my feeling would be that shouldn't this fix this pathway automatically for us? I mean we seem to have the remedy here, but I can tell you it is NOT seeming to work at least in arresting our symptoms of tics. Now I have mentioned that in November I switched to nasal spray form of this and possibly it was not a good form for us (totally my thinking, doc said it seems to be good for many patients), but lets say I am correct for my son, .... in April I went back to shots and he has had about 5 weeks of the shots again, so maybe it takes a little bit to totally kick in so to speak (that's what I'm waiting for) but I think by five weeks or so of starting our shots last year, that is when things got somewhat better (as i see in my journaling) not totally but the head jerking started to dissappear (and at that time we were just getting rid of high sensitivities on our Igg, i.e. corn, so could have been that too). BTW, that jerking is back in a big way for last couple months, so I am desperate here. I don't know what I am trying to say, but bottom line, why isn't our fix "fixing" this mutation (in the way of tics, anyway)?

 

And for what its worth, just to mention, I know Carolyn lsc was using this too (don't think she necessarily had the MTHFR, but it was part of her regimen) and she did tell me that she didn't think it necessarily was a factor in reducing tics. I got that from Syd'smom too, who was using that as part of the DAN docs therapy for her daughter a while back, and she eventually stopped the shots as she did not think they helped much (there is cost involved here, don't forget).

 

As far as doctor explaining anything, no I got not much except the part about he homocystene and it being implicated in heart and strokes. I think they are so fixated on this as a therapy for autism, that they just don't know how it helps in other issues such as tics.

 

What were you saying about the CBS, what was you lightbulb moment? Are you believing your kids have the CBS?

 

Faith

[kim]

Faith,

 

I'm thinking that my youngest son, and this finger/toenail issue is pointing to a problem with cysteine that he was born with. Now remember, oldest son had perfectly normal nails. It doesn't have to be present. I had a root canal btwn two sons birth. Removal of old amalgam replacement with new. They didn't cap it, since they said the tooth still appeared strong. Does that have anything to do with anything, I don't know. Just trying to think of what may have changed btwn the two, and why one had those nails and the other didn't. Sunshine's son had the problem nails, and a couple others here mention it, so I'm thinking in the study that I have been focusing on, the people with congenital hereditary form of bony growths, may have a different or more severe mutation or combo of things. It's just like using autism studies to find clues. Not autism, but some overlap. I'm thinking that we have the same problem with undersulfated GAGs but from a different source. In our case the CBS mutation makes sense. People with the hereditary form are usually short. My boys are both right near the tallest in their class. I'm wondering too, why they talk about "autistic" traits, not tics. Well, I'm not helping you out much here am I?

 

I understand your frustration Faith. I have seen cynocobalimin mentioned as a starting point on the Yasko forum and I think it was mentioned in the article that I just posted. Maybe the methyl form isn't right for your son. Maybe there are other missing pieces, but getting that pathway functioning right is the first step. I agree about "theories" becoming too focused on, and individual circumstances not being taken into consideration enough. There were things that needed specific supplementation of Sunshines son, besides what was needed for the CBS mutation.

 

Back to the "the study" on bony tumors for a sec. They said that the surface area of the AMPA lacked gluamate receptors (GluR1's), due to undersulfated heperan sulfate (i think). These receptors are sensitive to GABA, but my uderstanding GABA doesn't cross the BBB. They do respond (increase) to nicotine. Hmmmm.

I'm a little convinced there is a big clue there. I guess I'm bring that up because I wonder what neurons or receptors would be affected in a mthfr mutation. The same...or different? I can't help but to go back to the problem that you mentioned with your Dad. Have you ever had any kind of a lipid profile? I know MTHFR (although no clue about the type your son tested for) could result in an inability to excrete toxins, the whole methionine /glutathione thing, even if it doesn't affect sulfur metabolism. I'm wondering if oral or trandermal glut was ever recommended for your son. Honestly Faith, there could be SO many missing steps there. I can't remember what tests your son had?

 

I have a feeling this post is a jumbled up mess.

[CSP]

Kim,

 

His first set of tests showed deficient in B12, Folate was fine. The second set of tests showed his B12 went up just enought to be not deficient. Folate went down but still adequate.

 

Last week my husband and I were out on a date and he was to take his vitamins before we came home. He took one to many of the B12, and by the next day he was doing really good. I have since given him 1000mg of B12 and this week he has been really good all week. The only other thing he got was a probiotic, since his Igg came up high in the yogurt I stopped giving him kefir. So I'm not sure what has been the help here or how long this will last.

 

CP

[kim]

CP,

 

Interesting about the B12. Is that 1000 mgs or mcgs though? CP, you mentioned methylation markers being fine. If it isn't a really long list, could you say what they tested for?

 

 

Faith,

 

As far as doctor explaining anything, no I got not much except the part about he homocystene and it being implicated in heart and strokes

 

I could be totally wrong here, but I thought that I had read where the thermal (thermo?) form really wasn't significant where homocysteine was concerned?

 

Was that the only mutation that was checked for?

 

Look at this Faith. bolding mine

 

http://www.med.uiuc.edu/hematology/PtHomocysteinemia.htm

 

There is another type of mutation that can occur with MTHFR. This mutation results in a thermolabile variant (that means that the protein becomes inactivated with heat). A patient who is heterozygous for this mutation has no evidence of hyperhomocysteinemia or increased risk of thrombotic disorders. Patients who are homozygous (see * below) for the defect can develop hyperhomocysteinemia. In addition to the above causes, deficiencies in Vitamin B6 and folate can lead to increased levels of homocysteine. Other causes include certain medications and kidney disease.

 

and

 

 

The prevalence of hyperhomocysteinemia in the general population is not known. Studies looking at the prevalence of homozygosity (both (2) copies of the gene are mutated) for the thermolabile variant mutation in MTHFR have shown a prevalence near 15% in European, Middle Eastern and Japanese populations, compared with a range at or below 1.4% in African Americans. Patients who are heterozygous (1 copy of the mutated gene) are seen in 30-40% of the population.

[Sunshine]

I just quickly scanned the last few posts here, as I'm heading out on the boat with the family. Pardon me if I'm out in left field. I do not want to stir the pot or worry anyone, but I'll share some insight from our experience.

 

I just want to comment on the B12. We have been following the Yasko protocol, and my son needs LOTS (even more than 1,000 mg) of B12. However, Dr. Amy insists that certain forms of B12 are to be used, depending on the genetics of the patient. My son can NOT use Methyl B12, but needs LOTS of Hydroxy B12. I think for my son Cayano B12 is ok too, but not as good as Hydroxy.

 

Again, I don't want to rock the boat for anyone. My motto is if it's working, stick with it!