So, with all that has been going on lately, I though I should really do a little update on me. I am currently 23 weeks pregnant, things are going tremendously well. Despite my genetic mutation of MTHFR and more recently discovered additional variant (originally it was determined that I have the common variant of C677T) but I pushed to have both common variants tested (which had not been done in Canada for over five years) for the other most common variant A1298C and it turned out that I did indeed also have that one. What this means for me is a new title called Compound Heterozygous MTHFR and also an additional injection of 30mgs Lovenox (Blood thinner) each and every day (twice a day). In past posts I took a bit of time to explain what exactly MTHFR is, it's treatment and it's relationship to potentially having a child with Down syndrome, Neural Tube Defects and or other Chromosomal Abnormalities. It is very important to me (when I educate people about Ds) to also sometimes include MTHFR and its role simply because there are medical journals and studies which do suggest that a Folic deficiency or more specifically the genetic mutation MTHFR can be or make a person 2.6 fold more likely to have a baby with Ds. I have mentioned though, there is a wide discrepancy and debate on that topic AND even more so in the specific field of MTHFR (its role in recurrent pregnancy loss and even its treatment) but to me, it's very important to have all the facts regardless of speculation, debate or confirmed studies in either direction. Just as I do for Down syndrome, I have put together an online support group for MTHFR which contains explanations, resources and references for those curious about a topic in genetics that is not very well known at this point in time. Anyone curious about MTHFR is welcome to visit the site I have created, read, ask questions and even join.
Visit here: http://www.medhelp.org/forums/MTHFR-Methylenetetrahydrofolate-reductase/show/961?camp=msc&personal_page_id=1186587
What is MTHFR? Read here: http://www.medhelp.org/tags/health_page/139/Genetics/MTHFR?hp_id=1131
And for those interested in a written description that I put together, I have posted my document here:
Here is the majority of the information available in one document. I hope if you have been recently diagnosed this proves to be an effective aide to provide your health care provider(s).
MTHFR Gene Mutation
What is it?
The gene MTHFR (Methylenetetrahydofolate Reductase) encodes the protein MTHFR. Its job is to convert one form of folate (5,10-Methylenetetrahydofolate) to another form of folate (5-Methyltetrahydrofolate). 5-Methyltetrahydrofolate is used to convert Homocysteine (a "bad" amino acid) to Methionine (a "good" amino acid). Therefore, if MTHFR is not doing its job as well, homocysteine will not be converted to Methionine and will be elevated in plasma. Elevated Homocysteine has been associated with a variety of multi-factorial diseases.
Essentially what this means is that the genes that instruct MTHFR to convert homocysteine to Methionine are mutated and may not be capable of doing this important function. MTHFR is an enzyme that converts Homocysteine to an essential amino acid (Methionine). When the genes are mutated you may be lacking this enzyme. Your Homocysteine levels can possibly climb making the blood clot. Some doctors don't check for the MTHFR mutations and rely only on homocysteine levels. This isn't as reliable as testing for the mutations, because Homocysteine levels fluctuate (if you catch your level on a normal day, you may go undiagnosed).
What Type Do I Have?
With MTHFR, there are 24 known mutations but the two most common different genes are identified here for this mutation, and it's possible to be "heterozygous," "compound heterozygous," or "homozygous." The MTHFR gene mutation has varying degrees of possible implications. The order of potential (again, note that each person's severity can be different) severity from most to least is:
1. C677T & C677T (Two C Copies - C677T Homozygous)
2. C677T & A1298C (One Copy of Each The C & A - Compound Heterozygous)
3. C677T (One C Copy - C677T Heterozygous)
4. A1298C & A1298C (Two A Copies - A1298C Homozygous)
5. A1298C (One A Copy - A1298C Heterozygous)
It is also important to note that each of these common mutations can also be coupled with another mutation called Factor V Leiden which is known also as Antiphospholipid Syndrome. This mutation coupled with C677T is known to cause miscarriage up to 50% of the time. Also, of the two common mutations A1298C is the most commonly occurring in the population but C677T is the more problematic of the two with respect to health (vascular) and loss.
The MTHFR mutation is fairly common in the general population. Approximately 44% of the population is heterozygous and another approximate 12% are homozygous for the MTHFR mutation. Even though MTHFR mutations can affect each person very differently, compound heterozygous and homozygous MTHFR have the highest incidences of being linked to implantation failure, late term miscarriages, specific birth defects and overall vascular health. Whichever type of MTHFR you have, it should not be discounted, particularly if there is a personal or family history of any such incidences.
What Are the Implications?
Any and all of the mutations can affect homocysteine levels, but there is much dispute as to whether elevated homocysteine levels are actually needed in order for MTHFR to cause medical complications. Many other MTHFR patients have normal homocysteine levels; yet have had implantation problems, m/c(s), and/or stillbirth(s) due to clotting problems. So it is important to find out your Homocysteine levels (although again, normal doesn't necessarily mean all is well AND on any given day your Homocysteine levels can change making testing for this problematic). This is a serious field and MTHFR is a serious condition, so consulting an expert is wise.
Research shows that high homocysteine levels and/or those with the mutation show a higher propensity for thrombosis (blood clots), arteriosclerosis (hardening of arteries), Alzheimer's, stroke, heart attack, Fibromyalgia, migraines (especially with "Aura" migraines), osteoporotic fractures, bone marrow disorders and for those of child bearing years, it has found to be connected to higher incidences of Down syndrome, Spina bifida, other Neural Tube Defects, Trisomy, miscarriage, stillbirth, implantation failure, placental abruption, preeclampsia, higher incidences of autism, amongst others. The mutation C677T is specifically documented to be linked to these. Additionally, if you test positive consider having your parents, siblings, and any children tested, as well. There are a few positives to this disorder. Because folate is necessary for cellular division, there is support that shows having this disorder can actually help keep certain types of cancer cells from multiplying as rapidly, so there are some benefits from having this mutation.
Many doctors prescribe Folgard or other high level Folic Acid (PregVit 5 in Canada) supplements, which is a prescription vitamin supplement containing high levels of folic acid, B12 and B6. Because of the mutation, absorption of Folic Acid is hindered and anyone with MTHFR will require 200% more Folic Acid then a typical person. These vitamins are what the body essentially needs to convert Homocysteine to Methionine. To put this into perspective, the average multivitamin contains 400 mcgs , most prenatals have 800mcgs of Folic Acid. Any person with a MTHFR mutation are recommended taking 5 mgs. of Folic Acid/B vitamins (12 times the average multi-vitamin and 6 times more than prenatals). It is also recommended to begin taking a low dose (LD) aspirin (81 mgs) once a day, every day, for the rest of your life.
For those undergoing fertility treatments, often times the treatment includes Lovenox (low molecular weight heparin) or Heparin (both are anti-coagulants) during the cycle. If you have a history of implantation failure or early miscarriage, it is becoming more acceptable to use the protocol established by the well-respected Reproductive Immunologist Dr. Beers by beginning Lovenox (40mg/once a day) on cycle day 6 and continuing throughout the cycle. If pregnancy is confirmed, this dosage is likely increased (Typically up to 40mg/twice a day, but potentially higher doses are prescribed dependent upon blood work results since homocysteine levels tend to increase with pregnancy) and usage continues throughout your pregnancy. Approximately two to four weeks prior to birth, the patient is converted to Heparin and continues to take an anti-coagulant for another 6 weeks postpartum (typically switched back to Lovenox). During that time, you will typically be directed to take additional Calcium and Vitamin D, as anti-coagulants can cause bone loss (Heparin more so than Lovenox). Some doctors will recommend a bone scan after use is discontinued to ensure there are no bone density issues. While being treated with an anti-coagulant, you may be asked to discontinue taking the 81 mg. baby aspirin since the anti-coagulants will replace the need for the thinning property of the LD aspirin. The FDA has placed Lovenox as a category B. Lovenox is not expected to be harmful to an unborn baby. It is not known whether Lovenox passes into breast milk or if it could harm a nursing baby. Do not use Lovenox without telling your doctor if you are breast-feeding a baby. However, many doctors believe it is fine to breastfeed for the 6 weeks postpartum while still receiving Lovenox.
Note: This is not a replacement for physician related advice or for seeing a specialist educated on/about MTHFR mutations.
The definition of HOMOZYGOUS, COMPOUND and HETEROZYGOUS with respect to MTHFR:
Many people might have a diagnosis of some sort relating to MTHFR but not know what they mean exactly. I have put together a short descriptive explanation of what the common types of MTHFR are. Hopefully this helps to clarify what they mean for you.
Each person's body is made up Genes. Each gene has alternate pairs of Alleles. Alleles determine distinct traits that can be passed on from parents to offspring. Of the two copies, usually one comes from one parent and one comes from the other. When you have a MTHFR mutation, one or both of your alleles has a variant or mutation.
When you are diagnosed with a MTHFR mutation, you will fall under one of these categories - HOMOZYGOUS, COMPOUND or HETEROZYGOUS named with a particular type of one of the 24 known variants (likely one of the two most common C677T, A1298C both or other).
*Being Heterozygous means that you have one mutated copy of an allele which holds a particular variant and one normal allele. (Eg. Allele one is abnormal with C677T, Allele two normal)
*Homozygous means you have two identical mutated copies of the same gene with the variant. (Eg. Allele one is abnormal with A1298C, Allele two is abnormal with A1298C).
*Compound means you have two different types of variants, one in each allele. Since each gene has two copies, one from each parent, in Compound situations those pairs of genes or alleles will contain different variants - One will have one kind of variant and one will have another variant. Basically Compound situations mean that you host mutations in both alleles (both genes/alleles are abnormal) AND the mutations themselves are different from one another. This situation (Compound variants) is the same in terms of risk, health problem and treatments as a person who is Homozygous. In layman terms either situation means that both copies of your alleles are mutated, rather then heterozygous which means only one allele is abnormal.
The only compound situation that can occur can be COMPOUND HETEROZYGOUS, which means one allele has a mutated variant and the other allele has another different type. (Eg. The most common COMPOUND Heterozygous situation: MTHFR One Allele abnormal having C677T and one Allele abnormal having A1298C).
The reality is, each person can be affected differently or suffer varying degrees of health related issues for which ever case they have. A person who has ONE abnormal gene with a variant (heterozygous) may or may not have symptoms that cause concern just as a person who has two abnormal genes with same or different variants may or may not.
While in the world of controversy with MTHFR (as to whether it is problematic or not to health or pregnancy) the debate goes even further when doctors debate whether to treat a person who is heterozygous or homozygous and Compound. If you struggle with getting treatments, it is very important to discover whether your health care system tests for all variants and not just one alone. Because some doctors do not know that Compound variants act in exactly the same way as Homozygous mutations they can miss the fact that you have two mutated alleles if they only test for one type of variant. This is exactly what happened to myself when I was tested for ONLY C677T. Doctors then proclaimed that I appeared to only be Heterozygous and with many doctors, they don't want to treat anyone who only has ONE mutation because they don't feel it is a risk to health as much as having TWO mutated alleles. After demanding and suffering through the health care system, I did get a test for the other common variant A1298C and learned that I had that mutation as well. This changed the fact that I no longer only had ONE mutated allele but two, albeit two different types. For my pregnancy THIS changed my treatment dramatically and if it wasn't learned it could have affected the way my pregnancy continued or not. I stress that if you are in the investigation stages of testing that you ensure you are prepared to educate your physician in case a situation like this arises. Regardless and either way, do not allow your physicians to minimize your diagnosis if you only have one mutation. If you have symptoms, the reality is that they need to be treated or at the very least not ignored simply because it's heterozygous.
Sorry for the very LENGTHY in depth explanation, but I have had many moms asking me for information on the subject and I do feel it is very important to have all the information available (even if it still tends to be quite controversial in many locations). Please feel free to email or contact me if more information is needed.
Please note however, this information is a collaboration of much research and also personal experiences and opinion. It is NOT a replacement for actual medical information, treatment or professional medical advice from a doctor, physician or health care provider. All medical information you obtain should be taken up with your own health care providers or genetics specialist/departments. Under no circumstance should anyone substitute any of my information for legitimate health care. This information is for personal use/educational purposes only.