MTHFR mutation

[LNN]

Since DS's folate levels check out fine, does it naturally/automatically follow that his homocysteine levels are also fine? What questions should I be asking and should I be asking for more tests?

 

 

A person with a C677 mutation can have "normal" blood levels of folate and/or B-12. But with this mutation, they cannot convert (methylate) that folate (using B12 as a co-factor). At the point in the cycle where folate is methylated, there's a fork in the road.

 

Based on the body's needs and/or genetic abilities, one fork re-methylates folate (with B12) back into methionine and then into SAMe and eventually seratonin.

 

The other fork takes the homocysteine that's created by this process and ideally converts the homocysteine into cysteine and then into glutathione.

 

The question for people with a C677 mutation is whether the body is able to efficiently complete both of these steps/forks or if it just lets unmethylated folate build up in a big traffic jam. You could have tons of folate in your blood. If you're unable to methylate that folate into methylfolate, that folate is useless. People with two mutations of C677 (homozygous) only perform this methylation process at about 10%-20% efficiency. People with one mutation (heterozygous) perform this process at approx. 40-60% efficiency (estimates vary).

 

So homocysteine levels could be high even if your folate and B12 levels are normal. You should measure homocysteine directly.

 

The key for those with C677 (and this is not a Pandas mutation - 40% of the population carries at least one mutation) is to take methylfolate, not regular folate (and possibly avoid regular folate, since your body isn't able to process it). By taking methylfolate supplements, you've done the methylation process outside of the body and are providing the needed end result (methylfolate) which can then be used properly by the body.

 

Nancy, personal opinion - I don't think 400mcg is too high for your DD. However, I think a doctor might suggest a lower dose of methyl B12 - maybe 1000-2000mcg but every day. You want to keep things steady and give both methylfolate and methylB12 together, rather than days apart, with high and low troughs of B12. Maybe start with 400mcg methylfolate+1000 mcg methylB12 for a few weeks. Then increase to 800mcg methylfolate and 2000mcg methylB12 (but obviously run this by the doc).

 

Be aware that a log jam has been building in your DDs body. By supplying the needed methyl forms of folate and B12, you'll be lowering the level of the log jam. But this may cause a herx-like response intially. You have a lot going on and it may be difficult to tell what's what. To reduce the chances of ill effects, build slowly. For the first few weeks, you may even want to split doses and give half a dose in the morning and the other half in the later afternoon (B12 gives energy, so probably not something to give at bedtime). If you go slow, you may not even think it's helping right away. But if you're so inclined, you could discuss testing homocysteine levels as a benchmark and then re-test after a period of time to see if that drops.

 

Many doctors are aware of how homocysteine increases risks of heart disease, stroke and macular degeneration. Few understand the impact on mental health/seratonin. But your DAN should be of some help. Also bear in mind that months down the road, as methylation improves, any treatment dose of an SSRI may need to be adjusted downward, as the body may be making more seratonin and the need for reuptake inhibition may be less.

[dcmom]

LLM- According to your research, if one has a hetero C677 mutation, but homocysteine levels are normal- do you still consider supplementing with methyl folate (and B12)?

[Hopeny]

Below info from Dr. Jones' website will explain. You should see an integrated MD who knows how to treat MTHFR. You may want to check B, homocysteine, and glutathione levels. There is also a test you can take to check anti-cerebral folate abs. This is part of a research study at SUNY Medical Center. The cost is $100 (insurance will not cover). If you'd like more info on this study let me know.

 

From Dr. Jones Kids website:

"MTHFR is a common genetic variant that causes a key enzyme in the body to function at lower than normal rate.  This can lead to a variety of medical problems, when people with MTHFR are exposed to more toxins than their bodies can handle.  There are over 50 known MTHFR variants, but the two prime variants are called 677 and 1298, the numbers refer to their location on the gene.  The routine lab test for MTHFR variant only reports on 677 and 1298 as these are the most studied.  

 

"The 677 variant is associated  with early heart disease and stroke and the 1298 variant with a variety chronic illnesses.  The MTHFR is reported out as heterozygous or homozygous.  If you are heterozygous that means you have affected gene and one normal gene.  The MTHFR enzyme will run at about 55% to 70% efficiency compared to a normal MTHFR enzyme.  If you are homozygous then enzyme efficiency drops down to 7% to 10% of normal, which of course makes a huge difference."  

 

"The worst combination is 677/1298 in which you are heterozygous to both anomalies.  Many chronic illnesses are linked to this anomaly.  98% of autistic children have an MTHFR anomaly.  Fibromyalgia, irritable bowel syndrome, migraines, are all conditions associated with MTHFR anomaly." 

 

"MTHFR can make you susceptible to illness because the pathway is the primary source of glutathione production in the body.  Glutathione is the body's primary antioxidant and detoxifier.  People with MTHFR anomalies usually have low glutathione, which makes them more susceptible to stress and less tolerant to toxins."  

 

"As we age MTHFR problems get much worse due to the accumulation of toxins and the cumulative effect of oxidative stress, which ages our bodies."

 

      ~~~

 

Non mutated MTHFR is one of the leading regulatory enzymes of homocysteine metabolism.  Homocysteine metabolism is an extremely important factor of our metabolic systems. This process touches many aspects of our general health and is therefore very important. 

 

The MTHFR Mutation is a defective enzyme that hinders this process. The mutation of the MTHFR gene is directly related to hyperhomocysteinemia (high or elevated levels of homocysteine). 

 

High levels of homocysteine can be attributed to many conditions such as: 

 

The condition can lead to high rates of dementia /Alzheimer`s due to a decrease in vitamin B-12. 

 

High homocysteinemia can lead to coronary artery disease, common carotid atherosclerosis other Vascular Diseases.

 

Complications in Pregnancy Due To Neural Tube Defects. 

 

Atherosclerosis

 

Rheumatoid Arthritis

 

Downs Syndrome

 

Alcoholism

 

Osteoporosis

 

Neuropsychiatric Disorders

 

Non Insulin Dependant Diabetes

 

Early Pregnancy Loss

 

Spontaneous Abortion (Viable Fetus)

 

Placental Abruption, Low Birth Weight

 

Other Conditions

 

MTHFR mutation can be homozygous (2 copies) or heterozygous (1 copy), with more people being heterozygous and carrying only one MTHFR mutated gene. Compound heterozygous (one copy of each mutation). Homozygous, of course, can cause more issues and become more serious. 

 

It`s a fairly easy thing to test for by checking homocysteine levels in the blood. 

 

Treatment consists of simple vitamin supplements --- FolaPro L-methyl tetrahydrofolate by Metagenics, OR, 5 tetrahydrofolate or methyl folate. 

 

Longevity Plus, H.R. T. Plus with 5-tetrahydrofolate. 

 

Life Extension, optimized folate (5-MTHF).

 

OR prescriptions like:

 

*Deplin/ 7.5 mg l-methylfolate 

 

OR 

 

*Metanx-L methyl folate calcium (as Metafolin) 3 mg, Pyridoxal 5` phosphate 35 mg, methylcobalamin 2 mg. 

 

OR 

 

Methyl B-12 injections

 

The vitamin supplementation is lifelong.  After childbirth you may switch from prenatal to a women`s multivitamin.  

 

See a specialist to discuss whether you are a candidate for Lovenox.  Also, you may consider having a FULL antiphospholipid antibodies panel run. 

 

Many MTHFR patients also have Antiphospholipid Syndrome. If you have both, you are a likely candidate for Lovenox (injections of low molecular weight heparin) throughout a pregnancy to prevent clotting.

 

MTHFR mutations interfere with the body`s ability to absorb folic acid. Folic acid deficiencies for babies can cause neural tube defects like spina bifida. 

 

In addition, lack of folic acid can cause clotting-related problems. Since the teeniest, tiniest blood vessels are in the uterus, a female can have microscopic clots that don`t harm them, but cut off the blood supply to the embryo/fetus. This can cause implantation problems, m/c, or even stillbirth. So properly treating your MTHFR is critical. 

 

MTHFR is one of several different kinds of inherited thrombophilia. (Antiphospholipid Syndrome is acquired thrombophilia.) 

 

Please be sure to have your parents and siblings tested for MTHFR mutations as well. If positive, then they should discuss taking baby aspirin and additional Folgard as well (one Folgard per mutation.)  

 

During pregnancy adding extra folic acid is suggested beyond the 800 mg. 

 

Children will need a children`s multivitamin and later extra folic acid, too. 

 

There is controversy as to the importance of homocysteine levels when it comes to MTHFR mutations. 

 

MTHFR causes folic acid deficiency, which causes elevated homocysteine levels, which causes clotting problems, which causes infertility or miscarriage.

 

MTHFR causes folic acid deficiency, which causes clotting problems, which causes infertility or miscarriage which may or may not cause elevated homocysteine levels.

 

Homocysteine levels may be checked.  Homocysteine levels (particularly in young women) are not an accurate predictor of clotting troubles. 

 

Baby aspirin is a blood thinner (relatively mild). Lovenox (low molecular weight heparin) is an anticoagulant (slows clotting.) They have two very different functions in the body. Your doctor may or may not want you to use both.

 

AVOID Laughing gas/Nitrous Oxide - Nitrous oxide uses up vitamin B-12 can cause severe problems or death in people with MTHFR Disorder.

 

AVOID Bactrim DS- In pregnancy it is associated with increased incidence of cleft lip. Otherwise the system is depleted of Vitamin B-12.

 

AVOID SamE, an over the counter product as this S-adenosyl-methionine can further inhibit MTHFR.

 

C77TT is associated with an increase risk of esophageal cancer.

 

MTHFR Disorder is associated with an increased risk for postmenopausal breast cancer, schizophrenia, anxiety, bipolar disorder, migraines, and strokes.

 

It effects of seizures and medications used to treat them.

 

There is a reduced risk of non-Hodgkins lymphoma and acute lymphocytic leukemia in adults.

could you please send me info on the SUNY study?

[NancyD]

Here is a link to a press release about the anti-cerebral folate autoantibodies test at SUNY:

http://www.downstate.edu/news_releases/2011/news_release_full26.html

 

And here are a couple links to their study:

 

http://www.nature.com/mp/journal/vaop/ncurrent/full/mp2011175a.html

 

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715943/

 

 

 

Below info from Dr. Jones' website will explain. You should see an integrated MD who knows how to treat MTHFR. You may want to check B, homocysteine, and glutathione levels. There is also a test you can take to check anti-cerebral folate abs. This is part of a research study at SUNY Medical Center. The cost is $100 (insurance will not cover). If you'd like more info on this study let me know.

 

From Dr. Jones Kids website:

"MTHFR is a common genetic variant that causes a key enzyme in the body to function at lower than normal rate.  This can lead to a variety of medical problems, when people with MTHFR are exposed to more toxins than their bodies can handle.  There are over 50 known MTHFR variants, but the two prime variants are called 677 and 1298, the numbers refer to their location on the gene.  The routine lab test for MTHFR variant only reports on 677 and 1298 as these are the most studied.  

 

"The 677 variant is associated  with early heart disease and stroke and the 1298 variant with a variety chronic illnesses.  The MTHFR is reported out as heterozygous or homozygous.  If you are heterozygous that means you have affected gene and one normal gene.  The MTHFR enzyme will run at about 55% to 70% efficiency compared to a normal MTHFR enzyme.  If you are homozygous then enzyme efficiency drops down to 7% to 10% of normal, which of course makes a huge difference."  

 

"The worst combination is 677/1298 in which you are heterozygous to both anomalies.  Many chronic illnesses are linked to this anomaly.  98% of autistic children have an MTHFR anomaly.  Fibromyalgia, irritable bowel syndrome, migraines, are all conditions associated with MTHFR anomaly." 

 

"MTHFR can make you susceptible to illness because the pathway is the primary source of glutathione production in the body.  Glutathione is the body's primary antioxidant and detoxifier.  People with MTHFR anomalies usually have low glutathione, which makes them more susceptible to stress and less tolerant to toxins."  

 

"As we age MTHFR problems get much worse due to the accumulation of toxins and the cumulative effect of oxidative stress, which ages our bodies."

 

      ~~~

 

Non mutated MTHFR is one of the leading regulatory enzymes of homocysteine metabolism.  Homocysteine metabolism is an extremely important factor of our metabolic systems. This process touches many aspects of our general health and is therefore very important. 

 

The MTHFR Mutation is a defective enzyme that hinders this process. The mutation of the MTHFR gene is directly related to hyperhomocysteinemia (high or elevated levels of homocysteine). 

 

High levels of homocysteine can be attributed to many conditions such as: 

 

The condition can lead to high rates of dementia /Alzheimer`s due to a decrease in vitamin B-12. 

 

High homocysteinemia can lead to coronary artery disease, common carotid atherosclerosis other Vascular Diseases.

 

Complications in Pregnancy Due To Neural Tube Defects. 

 

Atherosclerosis

 

Rheumatoid Arthritis

 

Downs Syndrome

 

Alcoholism

 

Osteoporosis

 

Neuropsychiatric Disorders

 

Non Insulin Dependant Diabetes

 

Early Pregnancy Loss

 

Spontaneous Abortion (Viable Fetus)

 

Placental Abruption, Low Birth Weight

 

Other Conditions

 

MTHFR mutation can be homozygous (2 copies) or heterozygous (1 copy), with more people being heterozygous and carrying only one MTHFR mutated gene. Compound heterozygous (one copy of each mutation). Homozygous, of course, can cause more issues and become more serious. 

 

It`s a fairly easy thing to test for by checking homocysteine levels in the blood. 

 

Treatment consists of simple vitamin supplements --- FolaPro L-methyl tetrahydrofolate by Metagenics, OR, 5 tetrahydrofolate or methyl folate. 

 

Longevity Plus, H.R. T. Plus with 5-tetrahydrofolate. 

 

Life Extension, optimized folate (5-MTHF).

 

OR prescriptions like:

 

*Deplin/ 7.5 mg l-methylfolate 

 

OR 

 

*Metanx-L methyl folate calcium (as Metafolin) 3 mg, Pyridoxal 5` phosphate 35 mg, methylcobalamin 2 mg. 

 

OR 

 

Methyl B-12 injections

 

The vitamin supplementation is lifelong.  After childbirth you may switch from prenatal to a women`s multivitamin.  

 

See a specialist to discuss whether you are a candidate for Lovenox.  Also, you may consider having a FULL antiphospholipid antibodies panel run. 

 

Many MTHFR patients also have Antiphospholipid Syndrome. If you have both, you are a likely candidate for Lovenox (injections of low molecular weight heparin) throughout a pregnancy to prevent clotting.

 

MTHFR mutations interfere with the body`s ability to absorb folic acid. Folic acid deficiencies for babies can cause neural tube defects like spina bifida. 

 

In addition, lack of folic acid can cause clotting-related problems. Since the teeniest, tiniest blood vessels are in the uterus, a female can have microscopic clots that don`t harm them, but cut off the blood supply to the embryo/fetus. This can cause implantation problems, m/c, or even stillbirth. So properly treating your MTHFR is critical. 

 

MTHFR is one of several different kinds of inherited thrombophilia. (Antiphospholipid Syndrome is acquired thrombophilia.) 

 

Please be sure to have your parents and siblings tested for MTHFR mutations as well. If positive, then they should discuss taking baby aspirin and additional Folgard as well (one Folgard per mutation.)  

 

During pregnancy adding extra folic acid is suggested beyond the 800 mg. 

 

Children will need a children`s multivitamin and later extra folic acid, too. 

 

There is controversy as to the importance of homocysteine levels when it comes to MTHFR mutations. 

 

MTHFR causes folic acid deficiency, which causes elevated homocysteine levels, which causes clotting problems, which causes infertility or miscarriage.

 

MTHFR causes folic acid deficiency, which causes clotting problems, which causes infertility or miscarriage which may or may not cause elevated homocysteine levels.

 

Homocysteine levels may be checked.  Homocysteine levels (particularly in young women) are not an accurate predictor of clotting troubles. 

 

Baby aspirin is a blood thinner (relatively mild). Lovenox (low molecular weight heparin) is an anticoagulant (slows clotting.) They have two very different functions in the body. Your doctor may or may not want you to use both.

 

AVOID Laughing gas/Nitrous Oxide - Nitrous oxide uses up vitamin B-12 can cause severe problems or death in people with MTHFR Disorder.

 

AVOID Bactrim DS- In pregnancy it is associated with increased incidence of cleft lip. Otherwise the system is depleted of Vitamin B-12.

 

AVOID SamE, an over the counter product as this S-adenosyl-methionine can further inhibit MTHFR.

 

C77TT is associated with an increase risk of esophageal cancer.

 

MTHFR Disorder is associated with an increased risk for postmenopausal breast cancer, schizophrenia, anxiety, bipolar disorder, migraines, and strokes.

 

It effects of seizures and medications used to treat them.

 

There is a reduced risk of non-Hodgkins lymphoma and acute lymphocytic leukemia in adults.

could you please send me info on the SUNY study?

[LNN]

LLM- According to your research, if one has a hetero C677 mutation, but homocysteine levels are normal- do you still consider supplementing with methyl folate (and B12)?

JMO, as there's a lot I don't know...the MTHFR gene sits at a fork in the road.

Fork 1 oversees: homocysteine => cysteine => glutathione

Fork 2 oversees: remethylation of methylfolate/methylB12 => methionine => SAMe => seratonin

 

So if homocysteine levels are fine AND no clinical issues with seratonin, then I personally wouldn't supplement. But it is something I'd monitor periodically, particularly after puberty, in the year prior to trying to get pregnant, and in mid-life and after, due to the role MTHFR plays in miscarriages, neural tube defects, heart disease and stroke. But for a younger child, if the homocysteine levels and the seratonin related behaviors are ok, I'd probably just monitor once a year or re-test if something seemed to change. JMHO.

 

For my DD, we supplement because it's helped significantly with anxiety/mood swings and we have major family history with many, many homocysteine related health issues. But if you don't have either, then I think it becomes more discretionary.

[Dedee]

Just wanted to jump in on this topic because we also just found out that all three of our PANS children are MTHFR positive. My daughter and myself are Heterozygous C677t, my son is homozygous C677t, and my husband and my oldest son are compound heterozygous C677t / A1298. In addition ( and just on a hunch) I also tested them for pyrlouria and to my suprise, all three kids also tested positive for this. So between treating the C677t and the prylouria, my daughter has made huge progress with just the methyl folate, B-6, B-12, and zinc. The boys have been a little slower to come around but they were not as sick as she was to start with. One suggestion was that I wasn't giving them high enough doses because my daughter only has the single mutation and the boys both have double mutations. Possibly, but I haven't had much help from physicians yet so I am waiting till we go to the LLMD the end of this month and hopefully I can get more guidance then.

 

This is a very complex issue to comprehend and I am reading and learning every day. I am just so excited that I have found something that is showing some promise. I encourage everyone to read up on the prylouria also and if it sounds like it could be a possibility, do the very simple urine test. You can order it online and you don't need a physicians order. It has made a huge difference for my daughter. Thanks LLM!

 

Good luck to all of us "mutated" parents!

 

Dedee

Edited July 8, 2012 by Dedee

[dcmom]

LLM- thanks for your opinion- appreciate it as usual. Your answer is in-line with what I was thinking. I am planning to try some methylfolate on the daughter with the mutation....

[LNN]

DeeDee - that is so awesome!!! The pyroluria stuff is amazing - I couldn't believe the change in my son. So many years, so many intense and expensive procedures...and a stupid zinc/B6 pill ends up being the thing that does the trick. I am sooo happy for you and DD!

 

I've been taking time away from the forum for my own mental health, but as you can tell, mention MTHFR or pyroluria and I can't help myself. I do want to mention that for those who have these issues, treatment can bring incredible results. But I don't want to sound like it's everyone's answer. 20 people may get great results from IVIG and someone reading may feel compelled to do it for their child and be horribly disappointed (and broke). Likewise, not everyone is going to benefit from methylation supplements or pyroluria treatment. But they're such inexpensive tests (relatively) that I think it's well worth looking into and addressing if indicated.

 

Wishing your whole family a much deserved carefree summer!!

[LNN]

LLM- According to your research, if one has a hetero C677 mutation, but homocysteine levels are normal- do you still consider supplementing with methyl folate (and B12)?

JMO, as there's a lot I don't know...the MTHFR gene sits at a fork in the road.

Fork 1 oversees: homocysteine => cysteine => glutathione

Fork 2 oversees: remethylation of methylfolate/methylB12 => methionine => SAMe => seratonin

 

So if homocysteine levels are fine AND no clinical issues with seratonin, then I personally wouldn't supplement. But it is something I'd monitor periodically, particularly after puberty, in the year prior to trying to get pregnant, and in mid-life and after, due to the role MTHFR plays in miscarriages, neural tube defects, heart disease and stroke. But for a younger child, if the homocysteine levels and the seratonin related behaviors are ok, I'd probably just monitor once a year or re-test if something seemed to change. JMHO.

 

For my DD, we supplement because it's helped significantly with anxiety/mood swings and we have major family history with many, many homocysteine related health issues. But if you don't have either, then I think it becomes more discretionary.

DCMom-

Here is an opinion from an MTHFR guru:

http://mthfr.net/mthfr-mutations-are-more-than-high-homocysteine/2011/09/20/

 

He recommends testing S-adenosylhomocysteine (SAH) rather than relying on homocysteine. But I think in a child who's in remission like your DD, I'd still take a slow/low approach and just be aware of potential issues as she matures.

[bsimon3]

A million thanks to all who posted here on this topic. Learning much from you all.

 

LLM - what are the 'seratonin related behaviors' you spoke if? We have noted that DS seems to flare in the spring when the weather warms, the days are longer and we spend a lot of time outside following the long, dark winter as well as when we return from a mid-winter vacation in sunny FL. I have had a nagging hunch that it had something to do with seratonin levels spiking (and suddenly falling off as in the case of the mid-winter vacation), but I never had anything to back it up, nor did I know how to check if my hunch was correct. I wonder if this could be another piece of the puzzle.

[LNN]

Bsimon3- a lot of literature on MTHFR focuses on homocysteine and the risks of heart disease, stroke, macular degeneration - or chronic fatigue and how undermethylation of B-12 effects energy levels. What I tend to focus on is the downstream effect undermethylation has on seratonin production and mood regulation, because that's the primary symptom we deal with in my DD7. What I mean my seratonin issues is mostly mood fluctation and anxiety/OCD.

 

There's certainly a seasonal aspect to seratonin. There are several things that go into seratonin production - you need to monitor not just proper methylation but also nutritional intake. Vitamin D is also essential to many health functions, including seratonin synthesis. So it's not a simple thing to unravel. But from all I can gather, there can certainly be a seasonal aspect to seratonin synthesis. Lower D in the winter, less nutritional variety in the winter, changes in environmental allergens (certain molds/funguses/allegrens spike in the fall or winter, some spike in the spring or summer).

 

Personally, DD seems to fall apart every January and mid-summer. So it seems that maybe two different things are at play. In January, I suspect infection (she certainly has a PANS reaction to getting sick), Vitamin D, less fruits. In summer, I'm suspecting outdoor molds and increased dairy/sugar (too much ice cream et al that maybe tips her into an allergy or yeast situation). Treating MTHFR has helped but hasn't been a cure-all. At the moment, I'm trying to confirm/treat a yeast infection that's suddenly taken DD from 100% to 65% in a matter of weeks. So treatment has turned to both killing the yeast and helping detox (using charcoal to soak up die off toxins) and oxidative stress (using alpha lipoic acid to help her produce more glutathione). But we're still in for a bumpy ride for the next few weeks. But at least I know we're taking the MTHFR piece out of the equation - and that should help not only now but also as she matures and other MTHFR health risks (miscarriages, heart, etc) become issues.