Hello, I am fairly new to this forum and diagnosis, and quite frankly, I am lost, confused and in need of help with treatment. I have found that most research seems to be around the 677 gene, but I am homozygous for the a1298c gene mutation and haven't been able to find definitive answers about this particular defect and there is some debate that a1298c doesn't affect 5-MTHF activity and production but every scientific and academic source I read that describes this genetic mutation says it does. At least what I have come across is that the c677t gene affects enzyme activity to a much greater percentage along with other effects as well. I guess I am suspect about this because my doctor prescribed 15mg Deplin and that is all I took for a month and I had dramatic results then I started getting fatigue and headaches so I started doing some research and found out about MTHFR gene variances and just got tested for the 677 and 1298 only. I will provide more info to see if this helps any of you to help provide me and others in the same situation with some answers. I have been an fairly healthy and active/athletic person my entire life with some auto-immune issues;flushing and papular rosacea that I have under control from laser treatments, hypothyroid for the past 8 years that is well controlled with levothyroxine and a couple episodes that my doctor described as MS in nature and the possible early signs of MS. I had muscle tremors, decreased vision in one eye, confusion, etc. but they only lasted a couple months and went away and I only had about 3 or 4 episodes of that happening over the past 8-10 years (I am now 36 years old). MRI showed no problems what-so-ever. I had infertility issues, did IVF and now have two beautiful twin girls. I started to develop gestational hypertension towards the end of the pregnancy, but no severe problems. After the delivery I developed post-partum depression that did not respond well to a myriad of medications that my doctors dutifully kept trying to see what would help me. He finally suggested Deplin as he said he just read a study saying that helped some individuals with depression that were not responding to anti-depressants. I started taking 15 mg Deplin fo rthe first 2 weeks then changed to a generic form of l-methylfolate by Virtus pharmacies every evening before bed and within a couple days I felt better, but by about 4 weeks I felt AMAZING!! And I decreased my Pristiq from 100mg to 50mg over that same time. All of my smptoms were gone! It seems as though every part of me has become more agile, both my brain and body. My brain fog has lifted, memory and concentration has improved. I had dizzy spells and moments of profound confusion and what I called "brain freeze" where it seemed as though my brain would just stop for several seconds for a time out, that I no longer have. No more extreme fatigue and the heaviness I felt in my muscles and bones is gone. I was almost unable to exercise from the fatigue and muscle and joint pain. My irritability and anxiety have improved and I feel like I can really enjoy life again. The cognitive impairment I experienced bothered me the most because I used to be a very intelligent and highly functioning individual and I suddenly became an idiot after the birth of my twins 3 and a half years ago. The issue is I started to get headaches and fatigue and am starting to experience very mild episodes of lack of concentration and cognitive ability to think of the appropriate words and concise logical thoughts and arguments. It seems that I am still having a hard time conveying cogent thoughts to others without at least some extent of stuttering and stammering to get my thoughts across logically. I have improved so much I am reticent to complain, but because I have improved so much I am optimistic that I can find the appropriate treatment regime to really fix this! That is when I really started to research Deplin and l-methylfolate and came across this site and Freddd's recommendations to take active forms of B12 and l-carnitine fumarate and that I might possibly be "overmethyllating"...I have started taking these but I can't seem to get back to that sweet spot I was at and I want that back!! I do also take TMG, DMG, and potassium, but I am confused as to what dosages I should be taking. I would love to know what dose of these supplements and what time of day people take these: L-methylfolate methyl b12 adenosyl b12 potassium and does it matter if one takes acetyl-L carnitine or L-carnitine fumarate? Are amino acid supplements necessary? How necessary are the minerals zinc, selenium, manganese, molybdienum, etc as I have read those are beneficial but I feel I probably get enough through my diet... I eat a fairly good diet so I feel like I get my other needed vitamins and minerals as much as I have researched. Please let me know your thoughts and recommendations as to how to help with the fatigue and mental slowness I am still experiencing. I may be missing some other obvious symptoms as well that I don't even know to observe to give ideas as how to address these issues. Thanks so much!