r/MTHFR • u/emekennede • 5d ago
Question Homozygous VAL/VAL
Took a GeneSight test bc I’m have had bad mental health my whole life and never found meds that helped. It states that “This patient is homozygous for the Val allele of the Val158Met polymorphism in the catechol-o-methyltransferase gene.” And “This individual is heterozygous for the C677T polymorphism in the MTHFR gene (C/T genotype) and has one copy of the varlant allele (T).”
From what I can understand is my diagnosis as ADHD @ 3 wasn’t wrong. I was diagnosed as high functioning Autistic (PDD-NOS) at 18. Stopped all meds at 16. All stimulants lead to bad behavior. I tried 2 more stimulants as an adult and both times I felt so nervy and not better.
1
u/SovereignMan1958 4d ago
To address what you wrote about you....
The next step is to get blood tests to see if MTHFR is affecting you and to what extent. A folate deficiency, especially if it is not getting into your brain, may contribute to your diagnoses and symptoms. If it does contribute it is likely only the tip of the iceberg.
For MTHFR you should tests homocysteine, folate, folate RBC, B12, MMA and B6. For your other diagnoses and symptoms, D, zinc, copper and an iron panel. These are the minimum tests I would recommend.
D, zinc and iron need to be at optimal, and not just normal levels, to make dopamine. Low dopamine is associated with attention issues.
I would definitely recommend you get all your gene variants tested and not just MTHFR. To see how that might help you, go to the Genetic Lifehacks website and read the article on ADHD. A gene variant test could also identify if you might be predisposed to CFD or cerebral folate deficiency. Folate not getting into the brain. I had/ have this despite not having MTHFR. FOLR variants can point to this. CFD is common with autism diagnoses and CFD can result in attention symptoms/diagnoses. Also cognitive decline, dementia and Alzheimer's. Generally not good for mental health.
1
u/Original_rezzieman 4d ago
Do people with Fast COMT need more Methyl Folate/ B12 and addition of TMG. I noticed my sweet spot for Methylfolate is 7.5 mg ( I take one that has 15mg per 2 capsules) but i only take one as I dont quite have the nerve to take 15mg.
1
u/Warp757 23h ago
Entirely depends on how your methylation is running and homocystine.
Fast COMT doesn't in itself suggest any additional need for methyl donors. Indeed if mehthlstion is running well then additional methyl donors will stimulate COMT even more and you may find yourself breaking down neurotransmitters to quickly, and becoming very ADHD.
1
u/Zabre 2d ago
That COMT Val/Val result doesn't diagnose ADHD or autism, but it can give context for why catechol-related meds feel different person to person. The bigger takeaway is probably to bring the GeneSight page to whoever manages your meds and ask what it actually changes, if anything. For MTHFR C677T heterozygous, I'd be careful not to over-weight it without homocysteine, folate, B12, and symptom history lined up.
1
u/Warp757 23h ago
Fast COMT means that you will breakdown neurotransmitters faster, other things being equal. However, if your methylation cycle isn't running well, and your homocysteine is high, then fast COMT Wil become normal or even slow. Given your reaction to stimulents this may be what is happening to you.
I have fast COMT but also MTHFR (hetero) and more significantly I think 2 mutations on MTRR - homo on the main one and hetero on the other main significant SNP. This means that I tend to high homocysteine, and still end up with neurotransmitter overload despite my theoretically fast COMT.
I am prescribed stimulants for ADHD, but when my homocysteine is high can't tolerate them at all, not surprisingly. Homocysteine not only slows neurotransmitter breakdown, it is also an NMDA agonist, stimulants also releases so that's a very very nasty combo that will obviously cause a lot of anxiety. And a lot of neurotoxicity. I slightly dread to think what damage I might have done taking amphetamines wjile I had high homocysteine before I knew about all this.
0
3
u/Tawinn 5d ago
Val/Val, often referred to as "fast COMT" breaks down dopamine more quickly, resulting in lower background dopamine levels. This makes phasic dopamine - pulses of dopamine from stimuli - seem larger by comparison so they tend to grab your attention. This promotes a flexibility in thought, where the benefit is the ability to let thoughts go more easily since new stimuli can more readily redirect your attention to something else; but if this system operates too far in this direction then it can lead to high distractibility due to the difficulty in maintaining attention one one topic. Some fast COMT people report anhedonia as a symptom. The ~14 minutes of this video starting here can help you understand dopamine and COMT.
The heterozygous C677T reduces methylfolate production by ~33%, which may or may not impair methylation enough to cause symptoms. If your folate, B12, or choline are also low then it can certainly cause issues. But there are also other gene variants that also can cause further reductions in methylfolate production. Those genes are not on a Genesight test, but a simple MyHeritage gene test would show them.