MTHFR Homozygous for A1298C

[browneyesmom]

DD12 is in her third severe exacerbation. She is PANDAS - triggered by strep and complicated by an immune deficiency for IgA & IgG. Our Ped recently indicated he thinks we might be missing something and wanted to test for heavy metals, food intolerances, etc. We wound up testing several things (not foods as she is on IVIG r/t immune deficiency, so it would not be reliable information - he recommended Feingold for anti-inflammatory diet and we're going to look over Paleo also) and are just starting to get back some of the results.

 

For the MTHFR, she is homozygous for A1298C. I realize this means that her parents (my ex and I) are both heterozygous for this gene and it has possible implications for our health also. I know I need to look into that; however, she is the one struggling at the moment.

 

I'd appreciate input on where I can read up on how this relates to PANDAS, immune deficiency, etc. TIA

[browneyesmom]

I should say that we are at least heterozygous; it's certainly possible that one or both of us are homozygous and we may be heterozygous for C677T also. I'll bring this up with my doc at next visit and see what he thinks.

[fightingmom]

Denise, I posted a little bit ago on the facebook page a link to Dr. Jones' site. He is a Lyme doc, but the man knows his stuff. He gives a lot of information on the MTHFR genes, and some suggestions as to the common treatments. Here is the link:

 

http://sites.google.com/site/drjoneskids/mthfr

 

And, this seems to be more focused on autism, but I'm convinced some day we'll find links to all of this stuff:

http://findingtherootcause.blogspot.com/

[LNN]

Denise - my understanding is that the A1298 is the lesser problem than C677. The workaround that Yasko suggests for A1298 is to supplement with TMG. I know it's a big time investment, but the best way to put it all together for me was to watch Yasko's presentations. I bought her book and DVD set but I suspect this link has very similar info..

http://www.autismone.org/content/dr-amy-yasko-presents-assessment-metals-and-microbes-function-nutrigenomic-profiling-part-1-

 

It's quite long and you may need to watch in in more than one sitting or repeat a few times. It gets complicated. But you walk away with an appreciation for how everything can be intertwined.

 

Hats off to your pedi for being willing to go here with you! If nothing from your testing gives you an AHA moment, you may also want to look into pyroluria, which is a $70 urine test from Vitamin Diagnostics. It's the one deficiency I've never seen on yasko's list. But here's some info on it http://betterhealthguy.com/joomla/images/stories/PDF/kpu_klinghardt_explore_18-6.pdf

 

My heart breaks for you guys. Please know you're in my thoughts.

Laura

Edited April 6, 2012 by LLM

[fightingmom]

And more:

http://nwhealthcare.net/index.php?id=64

 

Along with this flow chart displaying related medical conditions:

http://www.mindmeister.com/12694596/mthfr-related-health-problems

Edited April 6, 2012 by fightingmom

[fightingmom]

In this blogL http://itsnotmental.blogspot.com/2008/06/nutrition-genes-and-brain-dysfunctions.html I found a link to this supplement company that makes hypoallergenic supps - also the activated form of folate that it seems necessary in many cases:

 

http://www.pureencapsulations.com/newscaps.asp?cap=20100511

 

"Metafolin® ((L)-5-MTHF) is stereochemically identical to naturally occurring 5-MTHF. Metafolin® does not require modification and can therefore execute the beneficial effects of folate regardless of MTHFR genotype. Metafolin® is also efficiently absorbed and assimilated. In a double-blind, randomized, placebo-controlled intervention study of 144 women, 5-MTHF supplementation resulted in a greater accumulation of 5-MTHF in red blood cells than equimolar doses of folic acid 6. Another advantage of Metafolin® is that 5-MTHF is the sole substrate for methionine synthase, which converts homocysteine to methionine to maintain vascular and neuronal health. In a placebo-controlled study of 30 women, 5-MTHF supplementation supported healthy homocysteine levels over a 3-week period 7. Contrary to folic acid, 5-MTHF readily traverses the blood-brain barrier to support neurological health. In a placebo-controlled trial of 123 individuals, 5-MTHF administered over 6 months promoted emotional well-being. 8 * "

Edited April 6, 2012 by fightingmom

[SSS]

Hello-

My dd also has double A1298C.

When our then DAN got the results, he actually didn't seem to think it was a big deal, and he knew a lot about MTHFR- but perhaps before hand because I had told him no way am I giving her shots, and her blood levels of B12 were on the high side, I had been supping with the B's, anyway.

Of course, showing high blood levels of B12 does not mean the body is converting it properly.

 

Okay, having said all that-

what I have been able to learn about A1298C (and this will be a cloudy and unprofessional explanation with no links)

We have to watch out for ammonia.

Yucca is an herb that clears ammonia, many bio-meds use it for this purpose, it should not be used more than 2 weeks at a time.

I went on Yasko's supplement site, searched-

'BH4' is suppose to help, but this is not a supp you can buy, although she recommends a liver supplement specifically for A1298C.

The other thing she offers are her RNA formula's-

Ingredients seem to be a secret, a scientific base I don't get, and expensive- 1 bottle (liquid) is $80.

Yep, I bought the bottle of RNA for A1298C, gave to dd every morning, slipped myself some (because I have one of these, who knows maybe two also, never been tested)

and honestly could tell nothing from it, personally won't buy again, have pondered the specific liver supp, which is good herbs.

 

So, I give her oral B-12 drops most days, supp some B complex.

 

Sure I'm not much help here, but if you learn anything, will you let me know?

 

The ammonia is a big piece. I am hoping the new OAT test I am waiting on measures ammonia levels.

If it's high, I'll get some Yucca.

[NancyD]

Ok, now I'm confused. On his site Dr. Jones says "AVOID SamE, an over the counter product as this S-adenosyl-methionine can further inhibit MTHFR."

 

I thought SamE was part of treatment for MTHFR, no?

Edited April 6, 2012 by NancyD

[fightingmom]

Ok, now I'm confused. On his site Dr. Jones says "AVOID SamE, an over the counter product as this S-adenosyl-methionine can further inhibit MTHFR."

 

I thought SamE was part of treatment for MTHFR, no?

 

It seems in some instances, yes. But, not all adelles of the MTHFR cause high homocysteine levels -- which SAMe would help decrease. I've seen in a few articles tonight that the heterozygous C677T specifically may not be high at all is not specific to hyperhomocysteine levels. So, maybe a person with heterozygous C677T actually has low homocysteine (methionine, I believe is a precursor to homocysteine and glutathione is part of this cycle too I think), supplementing with SAMe, NAC, methylcoblamin, etc. could in theory reduce the levels even further. I'm trying to figure this out, too. Just thinking outloud.

Edited April 6, 2012 by fightingmom

[NancyD]

Hmmm...very interesting. My DD is homozygous C677T. Cannot remember what her homocysteine levels are or when we last checked. We did try SamE back in August/September and DD's anxiety seemed to get worse but it was the beginning of the school year so it was not the optimal time to try a new supplement. I was going to re-try again this month. But after reading this I guess we should check her homocysteine levels first. Thanks for this info, fightingmom!

 

Ok, now I'm confused. On his site Dr. Jones says "AVOID SamE, an over the counter product as this S-adenosyl-methionine can further inhibit MTHFR."

 

I thought SamE was part of treatment for MTHFR, no?

 

It seems in some instances, yes. But, not all adelles of the MTHFR cause high homocysteine levels (I've seen in a few articles tonight that the heterozygous C677T specifically may not be high at all). So, if a person with heterozygous C677T actually has low homocysteine (homoecysteine, I believe is a precursor to methionine), supplementing with SAMe, NAC, methylcoblamin, etc. could in theory reduce the levels even further. Low homocysteine is also a bad thing and causes it's own issues.

[fightingmom]

Hmmm...very interesting. My DD is homozygous C677T. Cannot remember what her homocysteine levels are or when we last checked. We did try SamE back in August/September and DD's anxiety seemed to get worse but it was the beginning of the school year so it was not the optimal time to try a new supplement. I was going to re-try again this month. But after reading this I guess we should check her homocysteine levels first. Thanks for this info, fightingmom!

 

Ok, now I'm confused. On his site Dr. Jones says "AVOID SamE, an over the counter product as this S-adenosyl-methionine can further inhibit MTHFR."

 

I thought SamE was part of treatment for MTHFR, no?

 

It seems in some instances, yes. But, not all adelles of the MTHFR cause high homocysteine levels (I've seen in a few articles tonight that the heterozygous C677T specifically may not be high at all). So, if a person with heterozygous C677T actually has low homocysteine (homoecysteine, I believe is a precursor to methionine), supplementing with SAMe, NAC, methylcoblamin, etc. could in theory reduce the levels even further. Low homocysteine is also a bad thing and causes it's own issues.

 

No problem. I edited my post a little bit above to say that I'm still working on trying to piece this together myself, but I think I'm headed in the right direction. I think the homocysteine levels will be a big piece of the puzzle.

[LNN]

Nancy,

Fightingmom is helping me give birth to a huge AHA moment on this SAMe thing. That sentence in the Jones link and the other link really caught my eye too. They just say "don't take it" but don't say why and it's driving me mad! Remember last week when I posted that I gave DD one dose of NAC for mucus and her anxiety went thru the roof for days? I've known that such an abnormal response was important but couldn't figure out what it meant. Now, if NAC is doing the same thing as SAMe (DD is heterozygous C677T) then fightingmom may have given me the keys to the kingdom.

 

I had been supplementing methylfolate back in Jan. when we found out about the C677T but there was a lot going on and I didn't see much difference, attributed the bi-polar moods to high copper, and then she tested high on folate and I mistakenly figured it meant she was good in this dept (not realizing as S&S says that there's a difference between having folate in the system and being able to methylate it). Anyway, other things resolved (EBV) and we added tryptophan and she was doing really good. I've been thinking the tryptophan was working in the same part of the cycle as SAMe would. But now I find this diagram

http://www.heartfixer.com/AMRI-Nutrigenomics.htm

and see that SAMe is in circle #4 and tryptophan and tyrosine (which also helps her) is in circle #2 - the circle past any MTHFR blockage.

 

After our LLMD appt on Tuesday and because of a few comments earlier this week from MommaKath and S&S, I realized I should re-start the methylfolate. On Thursday, I gave her 500mcg, which is what I gave her in January. Her anxiety was a little high but not super high. Yesterday, I gave her the whole capsule (1 mg) and she was Linda Blair. Angry, bi-polar, hysterical fear about having to go upstairs alone to get socks, too anxious to let the dentist seal her molars (we had to leave), aggressive, tearful - a complete mess. Reading this thread made it click. This guy even says it's a normal response for some http://mthfr.net/methylfolate-side-effects/2012/03/01/

 

So I still need to figure out why SAMe/NAC is an issue. But I'm so excited that this confirms that the MTHFR issue is my daughter's key, just as my son's adverse reaction to zicam ultimately led me to his pyroluria and associated zinc deficiency. I feel like an excited puppy about to wet the floor! It's killing me that we have family coming tomorrow and our winter of functional cleaning had to give way to a major spring cleaning today, so I won't have much google time. But will let you know what I find.

[fightingmom]

Wow, LLMD, great link.

Okay, so my theory was so small in reality to the bigger picture. Homocysteine levels could be high or low, SAMe could help or hurt, NAC could help or hurt, Tryptophan, too. It all depends on where your child has a breach in the methyl cycle. Step1 leads to step 2, step 2 leads to step 3, etc. and there are some reverse flows in this cycle that remove toxins and help breakdown along the way. Our kids could all have a defect anywhere along the way in this cycle. If SAMe and NAC are used towards the end of the cycle in step 4 , but what if your child's mutation affects step 2 of the cycle? If step 2 isn't working properly, the other steps are thrown out of whack and some things may already be in excess or toxic within the cycle. Giving a supplement that converts in the wrong step or wrong direction could be throwing the entire cycle more out of balance and further throwing off dopamine or serotonin and other important neurotransmitters in the process. This would account for all of us that gave noticed that some supps that impact this cycle have made our kids bonkers.

 

Also, noted that some mutations of the gene make some kids more susceptible to heavy metal toxicity, specifically aluminum and mercury (interesting).

 

This page on the link from LLM posted explains it well but you sort of have to read the entire thing to comprehend it:

http://www.heartfixer.com/AMRI-Nutrigenomics.htm#MTHFR:%A0%205,10-Methylenetetrahydrofolate%20Reductase%20(%DE%205-Methyl-Folate)

 

So S&S, it looks like your issue is maybe with the first step with urea and sulphur - which explains the ammonia issue.

LLM, you see positive results with tryptophan, maybe step 2 should be your focus? But then again I think SAMe has sulphur and perhaps you are dealing with that urea/sulphur issue too?

 

I noticed in this link they had testing, which was expensive, but it seemed much more detailed than just the knowing which MTHFR gene mutation you are dealing with. That's good to know, but then it becomes more of a "then what?" and I think the key is in these other values listed in the sample report in that link.

Edited April 7, 2012 by fightingmom

[NancyD]

I too feel like methylation may be an important (and underlying) factor for DD16. She does well on NAC but it's possible her dosage may be a bit high (currently 1200 mg bid). She does fine with 10 mg 5-MTHF dosage (we titrated very slowly), but how do you know what is just the right dosage for your child? She is taking Allithiamine (B-1), B-3 (niacin), B-6, and B-12 (nasal spray). We just checked zinc and copper again recently but I have not yet seen results. Have to check on homocysteine levels. Any other labs to check?

 

Thanks for the links, Laura. Too early on a Saturday to look at the diagram for too long. Hurts my brain to decipher. I wish I had more of a science background. Please post whatever you find.

 

Nancy,

Fightingmom is helping me give birth to a huge AHA moment on this SAMe thing. That sentence in the Jones link and the other link really caught my eye too. They just say "don't take it" but don't say why and it's driving me mad! Remember last week when I posted that I gave DD one dose of NAC for mucus and her anxiety went thru the roof for days? I've known that such an abnormal response was important but couldn't figure out what it meant. Now, if NAC is doing the same thing as SAMe (DD is heterozygous C677T) then fightingmom may have given me the keys to the kingdom.

 

I had been supplementing methylfolate back in Jan. when we found out about the C677T but there was a lot going on and I didn't see much difference, attributed the bi-polar moods to high copper, and then she tested high on folate and I mistakenly figured it meant she was good in this dept (not realizing as S&S says that there's a difference between having folate in the system and being able to methylate it). Anyway, other things resolved (EBV) and we added tryptophan and she was doing really good. I've been thinking the tryptophan was working in the same part of the cycle as SAMe would. But now I find this diagram

http://www.heartfixer.com/AMRI-Nutrigenomics.htm

and see that SAMe is in circle #4 and tryptophan and tyrosine (which also helps her) is in circle #2 - the circle past any MTHFR blockage.

 

After our LLMD appt on Tuesday and because of a few comments earlier this week from MommaKath and S&S, I realized I should re-start the methylfolate. On Thursday, I gave her 500mcg, which is what I gave her in January. Her anxiety was a little high but not super high. Yesterday, I gave her the whole capsule (1 mg) and she was Linda Blair. Angry, bi-polar, hysterical fear about having to go upstairs alone to get socks, too anxious to let the dentist seal her molars (we had to leave), aggressive, tearful - a complete mess. Reading this thread made it click. This guy even says it's a normal response for some http://mthfr.net/methylfolate-side-effects/2012/03/01/

 

So I still need to figure out why SAMe/NAC is an issue. But I'm so excited that this confirms that the MTHFR issue is my daughter's key, just as my son's adverse reaction to zicam ultimately led me to his pyroluria and associated zinc deficiency. I feel like an excited puppy about to wet the floor! It's killing me that we have family coming tomorrow and our winter of functional cleaning had to give way to a major spring cleaning today, so I won't have much google time. But will let you know what I find.

Edited April 7, 2012 by NancyD

[SSS]

I tell you, it is confusing for me, too!

Double A1298c - found a homeopathic capsule supplement of BH4- but for this particular deal, it says it boosts the neurutransmitters-

Well, had a recent neurotransmitter test, dd is off the chart high dopamine, AND has very high seratonin.

What the heck to do with that?

My former LLMD was somewhat in shock with the levels- I was asking for low dose clonidine, because things at home are unmangable, to the point that after 3 years of bio -med I'm asking for a pharmacutical, I have tried everything natural- 5-HTP, Kava, on and on, with no results or worse, and clonidine is a mild, no black box warning drug,

this Dr. said okay, give you script to try, but the only other thing I can think of that may help you is

Risperadol! Which is heavy duty, big fat side affect brain effecting drug.

Also did an amino acid profile with this Dr. said methionine is very low- taurine was okay, because I used to supplement that for her.

So see, I have NO idea what to supp.

Also, double A1298c does not produce high homocysteine levels.

All I really know with our specific mutation is to check for high ammonia.

Dd's transmitters are all high.

This Dr. laid out the MTHFR chart to me, the circles that make your head spin-

but....

I am weary of buying more expensive supps on my own, trying for hit or miss, so often a miss.

I think very few Dr.'s really know the great, exact details of MTHFR, especially without the C677T.

 

Or maybe it's just me.

By the way, the clonidine is also a no go with her.

Sorry to be Debbie Downer, at a low spot.

Edited April 7, 2012 by S & S