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Help me help my son... please!

Discussion in 'Genetic Testing and SNPs' started by pkuu, Jun 21, 2014.

  1. pkuu


    My 12-year-old son has severe apraxia (mostly resolved) and some attention issues (although doctors have told me he is NOT ADD/ADHD). He is diagnosed dyslexic with a short term memory at the 2nd percentile, but he manages to read at grade level. He's always had trouble getting over colds, but last Feb. was the worst. He was horribly exhausted (slept 15 hours a day), headache 24/7, so dizzy he was sometimes crawling across a room, couldn't pay attention to anything, and worst of all, he would pass out several times a day. (Some people told me he didn't really pass out, that he was falling asleep. I'm not sure what the difference is, but he would crumple to the floor as he walked across a room.) He was off school for three weeks straight and I really think he was dying.

    I took him to doctor after doctor, who ran all sorts of tests and told me he was fine. Finally in desperation I took him to a naturopath, who "prescribed" mega-doses of B-12 drops (the kind you put under your tongue). Within 24 hours the passing out, the dizziness, and the headaches were history. Then the real miracle began. He told me, "I feel stronger, and sharper, and smarter" (his words). He started remembering to turn in his assignments. He checked out chapter books-- and read them. He smiled and laughed. He ran up the stairs. He lost his sallow complexion and I swear his head grew 2 inches in circumference.

    So obviously he had some kind of serious B-12 deficiency, even though the pediatrician's B12 blood test said his B12 was on the high side. I ordered the 23 and me test on him and ran through the results on genetic genie. (Our naturopath is going to look at the results too, but she cautions me that she is no expert. And since this is my kid's life we are taking about, I want to know as much as possible!)

    MTHFR A1298C
    COMT V158M
    COMT H62H
    VDR Taq
    MAO-A R297R
    MTRR A66G

    VDR Bsm
    MTHFR 03 P39P
    MTR A2756G
    CBS A360A

    There were also several "no calls," but I don't know which ones at the moment.

    I read somewhere that if you have both the MTRR A66G and the MTR A2756G mutations, you can need up to 5000 mcg/day of B12. That's about what my son has been taking, and he weighs 85 lbs. Also I have read that the CBS A360A depletes B12 stores and that BHMT mutations uses B12 to get their job done. . Am I interpreting this correctly-- my son is absorbing less than 10% of the B12 that goes in him, and then he has four other gene mutations that use up his stored B12 faster than normal?

    Also could anyone tell me what else he should be taking? Obviously if the B12 is such an issue he probably has other absorption issues-- but then again, he's a 12-year-old boy and I just can't ask him to take a whole bunch of different supplements every day. (The B-12 is bad enough.)

    OH, and the naturopath did a food sensitivity test. The food sensitivities scale ranged from 1-5, and he came out with 3s on dairy, eggs, and gluten. We have been trying an eggs- gluten- and dairy-free diet, but he's a 12-year-old boy and I know he cheats when he's away from home. I'm not convinced the diet has made much difference, but then again I don't know how closely it's been followed.

    Any advice any of you can give me would be greatly appreciated...
    taniaaust1 and Valentijn like this.
  2. Valentijn

    Valentijn Senior Member

    MTRR A66G reduces B12 recycling to about 30% of normal. I've got the same homozygous mutation :D

    I don't see any other real problems on his results, though the Yasko Fanclub will disagree (especially regarding CBS) and suggest all sorts of tedious and expensive "solutions" based on 0 published evidence and some massive and absurd misinterpretations of unrelated research.

    There are a few possibilities. One is that all of his problems were due to a B12 deficiency. This seems unlikely, especially if he's still having symptoms. But it's possible that as he continues to supplement B12, things will continue to improve.

    Another possibility is that he has additional B12 issues. Since his symptoms seem too extreme to be completely blamed on his MTRR A66G mutation (presuming he isn't vegetarian), it might be worthwhile to look for other mutations. has a list of some.

    Or additional methylation issues might be present. has a list of MTHFR mutations known to cause problems, and some very rare ones as well.

    If you had ordered the 23andMe test in the past few months, then it's using a new chip with fewer SNPs being tested. So lists developed for the older chip will give you quite a few "no call" results.

    If suspecting a rare genetic disorder, can pull out very rare alleles. The most interesting ones would usually be homozygous or starting with "i" instead of "rs".

    Regarding diet, the gluten+egg+dairy issues pretty much kills off all the interesting dessert prospects, which might be especially hard on a 12 year old boy. Maybe having some gluten-free vegan treats would help a bit in removing outside temptation. There's excellent coconut ice creams on the market, and there's some pretty good recipes for gluten-free baking floating around now, if there's nothing available commercial in your area.
  3. taniaaust1

    taniaaust1 Senior Member

    Sth Australia
    MTHFR mutations can cause big issues, I dont know much thou about the ones your son has.

    I suggest also to consider what the MTHFR mutations are doing esp since he's got 3 different mutations of that (I have a different MTHFR mutation but for it I also need B12!). The best for info on MTHFR stuff is probably
  4. taniaaust1

    taniaaust1 Senior Member

    Sth Australia
    According to Dr Ben Lynch (MTHFR expert).. Your sons homo MTHFR mutation could cause

    Possible symptoms associated with A1298C MTHFR mutations:
    • hypertension
    • delayed speech
    • muscle pain
    • insomnia
    • irritable bowel syndrome
    • fibromyalgia
    • chronic fatigue syndrome
    • hand tremor
    • memory loss
    • headaches
    • brain fog
    Possible signs associated with A1298C MTHFR Mutations:
    • elevated ammonia levels
    • decreased dopamine
    • decrease serotonin
    • decreased epinephrine and norepinephrine
    • decreased nitric oxide
    • elevated blood pressure
    • muscle tenderness
    • ulcers
    • pre-eclampsia
    Possible conditions associated with A1298C MTHFR mutations:
    • fibromyalgia
    • chronic fatigue syndrome
    • autism
    • depression
    • insomnia
    • ADD/ADHD
    • irritable bowel syndrome
    • inflammatory bowel syndrome
    • erectile dysfunction
    • migraine
    • Raynaud’s
    • cancer
    • Alzheimer’s
    • Parkinson’s
    • recurrent miscarriages
  5. taniaaust1

    taniaaust1 Senior Member

    Sth Australia
    I think Ive read that B12 also expands blood volume.. so its also possible that he had some kind of dysautonomia and the B12 boosted his blood volume. eg POTS or another kind in which low blood volume is involved.. which was causing his passouts and other symptoms???. Something like POTS (postural orthostatic tachycardia syndrome) has main symptoms of exhaustion/tiredness, memory and brain issues, dizziness, headaches (due to not enough blood getting to the brain when upright) and can cause pass outs.

    Anyway.. there is several possible reasons why that B12 may of helped him.
  6. Daffodil

    Daffodil Senior Member

    One suggestion is to see a doctor who specializes in autism and related disorders. perhaps dr. bradstreet, if you can afford. also, get the ELISPOT test for Borrellia to rule out Lyme.

    B12 can result in remarkable improvement but I am not sure it is addressing the cause of the problem....if anyone knows what it is
  7. MTR + MTRR is the "B12 double whammy". Heartfixer has more info on this (see the link in my signature).

    The serum B12 test is useless. A high result can indicate a functional B12 deficiency.

    What type of B12 is he taking (cyano, hydroxy, methyl or adenosyl)?

    Can you also post his detox SNPs (use

    Tag me with @caledonia, so I'll get an alert and be able to respond.
  8. pkuu


    Thank you-- all of you-- for your help.

    I am interested in knowing how rare these mutations/variations are. Does almost everybody have some kind of MTHFR variation or is my son's profile fairly rare? And if it's rare-- how rare is it?

    Valentijn, my son has several of the "interesting" MTRR variations and also several of the "interesting" MTHFR variations.. How do I find out which of these are important and why?

    Taniaaust1, thanks for the link. Looks like a great site-- I will have to spend some time there. Funny thing-- when my son was at his worst, I was convinced he had POTS (let's face it the symptoms were the same). But he spent a whole afternoon being tested on a tilt table in a pediatric cardiologist office, and they said he didn't have POTS.

    Daffodil, I'm convinced my son is somewhere on the autism spectrum, but if so he's EXTREMELY high functioning. He has some minor sensory issues, but he has plenty of friends and has no problem functioning in school or social settings. The Lyme disease was a consideration, but the B12 was such a crazy improvement that we never followed up on that.

    @caledonia, my son is now taking a dropperful of methyl B12 drops twice a day. Our naturopath said that was the best for absorption. And here is his genetic genie detox profile. He had only one homozygous "bad" result, the rs 1135840..

    CYP1A1*2C A4889Grs1048943TT-/-
    CYP1A1 m3 T3205Crs4986883TT-/-
    CYP1A1 C2453Ars1799814GG-/-
    CYP1A2 164A>Crs762551AA-/-
    CYP1B1 L432Vrs1056836CG+/-
    CYP1B1 N453Srs1800440CT+/-
    CYP1B1 R48Grs10012CG+/-
    CYP2A6*2 1799T>Ars1801272AA-/-
    CYP2C9*2 C430Trs1799853CC-/-
    CYP2C9*3 A1075Crs1057910AA-/-
    CYP2D6 S486Trs1135840GG+/+
    CYP2D6 100C>Trs1065852AG+/-
    CYP2D6 2850C>Trs16947GG-/-
    CYP2E1*1B 9896C>Grs2070676CC-/-
    CYP2E1*1B 10023G>Ars55897648GG-/-
    CYP2E1*4 4768G>Ars6413419GG-/-
    CYP3A4*2 S222Prs55785340AA-/-
    CYP3A4*3 M445Trs4986910AA-/-
    CYP3A4*16 T185Srs12721627GG-/-
    GSTP1 I105Vrs1695AA-/-
    GSTP1 A114Vrs1138272CC-/-
    SOD2 A16Vrs4880AG+/-
    NAT1 R187Qrs4986782GG-/-
    NAT1 R64Wrs1805158CC-/-
    NAT2 I114Trs1801280TT-/-
    NAT2 R197Qrs1799930GG-/-
    NAT2 G286Ers1799931AG+/-
    NAT2 R64Qrs1801279GG-/-
    NAT2 K268Rrs1208AA-/-

    Again, thank you everybody and if anyone has any more observations, I'd love to hear them...
    Last edited: Jun 24, 2014
  9. pkuu


    One more thing-- can anyone tell me the difference between SNPs that start with rs and the ones that start with an I?
  10. Valentijn

    Valentijn Senior Member

    Can you list them? Then I can check my notes to see if I have summaries for the impact of those and links to the research.
  11. Valentijn

    Valentijn Senior Member

    "rs" numbers are the conventional way to label SNPs. It's used by everyone.

    23andMe uses their own "i" numbers to label SNPs which don't have a "rs" number yet. But mostly the use "i" numbers for known pathogenic mutations, to make it much harder for people to investigate their own genetic data. It's the one thing I really hate about 23andMe.
  12. pkuu


    Ok, here are the "interesting" MTRR variations:

    A 66 G homozygous GG
    G827A hetereozygous AG
    G1515A Homozygous AA
    A664A homozygous GG

    Here are some of the "interesting" MTHFR variations. I've starred the ones listed as "missense mutations," whatever that is).

    * A3301G Homozyogus GG
    A372C Homozygous TT
    G35A Heterozygous CT
    * A1298C Homozygous GG
    Last edited: Jun 23, 2014
  13. Valentijn

    Valentijn Senior Member

    A66G - rs1801394 (GG = 14.1%) GG has 1/3 to 1/4 (30%) of the usual effectiveness at repairing MTR:
    G827A - rs3776467 (AG = 49.6%) G allele results in slower methylation (indicating less MTRR activity):
    G1515A - rs7703033 (AA = 6.1% prevalence) A allele indicates 10% higher homocysteine (indicating less MTRR acitivity):
    A664A - rs1802059 (GG = 6.2% prevalence) GG indicates a greater risk of nephrotoxicity, which might be associated with slower MTRR function:

    A3301G* - rs2184226 (GG = 0.2% prevalence) G allele is associated with increased ovarian cancer risk, which is removed with folate supplementation (indicating less MTHFR activity):
    A372C - rs4846049 (TT = 9.6% prevalence) TT is a downregulation, and the T allele is associated with more Cerebral Palsy and mental retardation (indicating less MTHFR activity):
    G35A - rs1476413 (CT = 34.1% prevalence) T allele is associated with more cleft lip and retardation (indicating less MTHFR activity): ?
    A1298C* - rs1801131 (GG = 5.2% prevalence) G allele is associated with more Turner Syndrome (probably indicating less MTHFR activity) and reduces MTHFR activity by 50% when combined with at least some other MTHFR mutations, but hasn't been shown to be a problem with the ones your son has: research summary at

    So there might be some significant additional reduction in MTRR activity. MTHFR activity also might be reduced a fair bit. So it could help to try supplementing some methylfolate (not folic acid) in addition to the B12.

    The good news is that both problems (if they are problems) are completely correctable with supplementation :D

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