Given your snps, I think there's a lot of benefit to you from exploring methylation deeply. The jitteriness without RLS sounds like neurotransmitter issues that could be addressed with the right protocol for your snps.
There's probably a million things that have insomnia as a symptom, but Lynch has it high on his list for a1298c:
http://mthfr.net/mthfr-a1298c-mutation-some-information-on-a1298c-mthfr-mutations/2011/11/30/
Heartfixer says this about the mutation:
MTHFR A1298C: 5,10-MethyleneTetraHydroFolate Reductase (Þ BH4)
The MTHFR C677T defect effects the “forward reaction”, the conversion of THF in to 5-methyl folate. MTHFR A1298C has no adverse affect on 5-methyl folate production, but it does compromise the “backward” reaction, whereby 5-methyl folate is converted back in to THF, in the process generating one molecule of BH4.
Individuals with abnormalities in CBS and BHMT will be low in BH4, as it is being used up detoxifying ammonia that these defects have generated, so their combination with MTHFR A1298C leads to a BH4 deficiency double whammy.
DHPR is the enzyme that regenerates BH4 from BH2. It is poisoned by mercury, lead, and especially aluminum. These toxins are wide spread in our environment, and individuals with Methyl Cycle abnormalities have particular trouble dealing with them.
The result is a progressive drain on BH4, a progressive impairment in neurotransmitter production, and conversion of arginine not in to nitric oxide but instead in to free radicals such as superoxide and peroxynitrite.
We treat MTHFR A1298C with 5-methyl folate supplementation (aiming to push the reaction backwards) and, after your other Methyl Cycle challenges have been addressed, with nutritional doses of BH4.
Metal detoxification will help here and with every other biochemical function in your body, and will be part of your overall program. We will also endeavor to decrease your need for BH4. If you are COMT (-/-), we can provide nutritional support to help maintain dopamine levels, such that you will need to use less BH4 to generate more. If you are MAO A (-/-), we can do the same thing with serotonin precursors such as high tryptophan foodstuffs.
You do have COMT and MAO A involvement, so treatment might be trickier. You have enough homozygous snps of significance, that I would consider pursuing treatment with someone very familiar with methylation issues. It's a quality of life issue at the very least, and depending on your coronary health markers, possibly a longevity issue.
I guess it doesn't surprise me that b12 alone wouldn't provide a long-term fix. It's one element of a super complicated system and you have a fairly complicated set of mutations to that system. You clearly need more mb12 and more folate based on MTR and 1298, MAO A may be creating histamine issues, those four MTHFRs could be quite significant, though I don't know.
I am quite resistant to the idea of metals/mercury detoxxing (so much controversy surrounding the need for it and the physical demands/expense of amalgam removal), but that comes up with a1298 on both Lynch and Heartfixer, so it might be worth pursuing at soem point.
If it were me (and I guess it is me, but I'm showing some decent improvements right now, so I'm willing to give the Deadlock quartet protocol more time) I would consider a trip or a phone consult, if he'll do it, with James Roberts, or another really well-versed practitioner. Life is short, particularly for those of us on the back nine and it's not worth pinching our pennies while our body struggles and perhaps declines.
And honestly, I saw nothing but negative impacts from the first two months of my methylation protocol work. That could have been detox/symptom return and part of a healing phase, or it could have been me being way out of whack with folate vs. mb12.
Then I started taking the mb12 shots and suddenly all my major symptoms are improving, oh, maybe 30-35 percent right now (with some down days sprinkled through the last two weeks). One of the things I've found with this symptom improvement is I'm able to notice when other factors might be affecting my wellbeing -- in particular I feel like I'm beginning to be able to tease out some diet-related effects that were lost in the brain fog and overall noise of the complex disregulation.
It's possible you need to get to a threshold with folate before something kicks into gear for you. I see advice to kick up folate 200 mcg every 2-3 days and watch for symptoms. I'd do that, but I would be sure to kick up MB12 by 1,000 mcg for each step up in folate, to be sure you're absorbing enough of it to match folate.
I of course, defer to more experienced voices here, but that's my 2 cents worth.
sue
