• Autosomal recessive inborn error of methionine metabolism usually caused by a deficiency of cystathionine beta-synthase and associated with elevations of homocysteine in plasma and urine; clinical features include a tall, slender habitus, scoliosis, arachnodactyly, muscle weakness, genu varis, thin blond hair, malar flush, lens dislocations, an increased incidence of mental retardation, and a tendency to develop fibrosis of arteries, frequently complicated by cerebrovascular accidents and myocardial infarction.
• Short description: Sulph amino-acid met dis.
• ICD-9-CM 270.4 is a billable medical code that can be used to specify a diagnosis on a reimbursement claim.

We take out that description and put in MTHFR or MTHFR 677 heterozygous, MTHFR compound heterozygous 677/1298, or MTHFR 1298 homozygous. The detail is useful in the problem list, since we treat different variations differently.

2. Do Insurance companies pay for MTHFR testing?

Ans. Unfortunately, the answer  is often no, but that has been changing we are seeing more and more insurance carriers pay for this testing. They certainly should since methylation issues are treatable and treatment can help mitigate or prevent much more expensive problems both immediately and in the future.

3. Do you treat all MTHFR anomalies the same way?

Ans. No, when the 677 variant is present we have found that L-methyl folate (Deplin) works best. We use methyl B12 when the 1298 variant is present.

4. Can you expect side effects with the use of Deplin or L-methyl folate?

Ans. Yes, there are several common side effects. Deplin can cause an upset stomach in some people is taken on an empty stomach. If the Deplin dose is too high, it may cause the body to dump excessive amounts of toxins into the system. This can cause side effects. These can be reduced or eliminated in most cases by using a binding agent to bind up toxic bile being released by the liver or starting at a lower dose and working up to the maintenance dose.

5. I Looked up Deplin and it is used for depression and I don’t have depression should I still take Deplin?

Ans. If you have a MTHFR 677 anomaly, then you will benefit from L-methyl folate (Deplin). The FDA is fairly simplistic in their thinking, which is one diagnosis, one drug. If you are want to use it for something else, then according to the FDA’s way of thinking you need a different drug name. For example Zyban (bupropion) is a drug to help with smoking cessation, the exact same medication is used as anti-depressant under several different trade names: Wellbutrin, Voxra, Budeprion, Prexaton, Elontril or Aplenzin.

Physicians understand that a drug may be used for multiple medical problems, this is called “off label prescribing.” FDA has approved Deplin as a medical food that has demonstrated benefit for the treatment of depression. This does not mean Deplin is only useful for depression. The main reason for using Deplin when MTHFR is present is because it helps methylation and indirectly raises glutathione. Low glutathione is the root cause of many chronic illnesses.

6. Are over the counter versions of methyl folate just the same as the brand name Deplin?

Ans. For the most part the answer is no, with some exceptions. There are racemic versions of methyl folate being marketed as equivalent to L-methyl folate (Deplin). They are not. The racemic versions contain both D-methyl folate and L-methyl folate. The D-methyl folate (non active form of folic acid) can compete at the binding site making the L-methyl folate less effective. There are some forms L-methyl folate being marketed OTC.

Definition of racemic: Of, relating to, or constituting a compound or mixture that is composed of equal amounts of dextrorotatory and levorotatory forms of the same compound and is not optically active.

7: What is a SNP?

Web definitions:

A single-nucleotide polymorphism (SNP, pronounced snip; plural snips) is a DNA sequence variation occurring when a single nucleotide – A, T, C or G – in the genome (or other shared sequence) differs between members of a biological species or paired chromosomes in a human.

Single nucleotide polymorphism abbreviated as SNP and pronounced snips. Means one nucleotide or setting on the gene has a variation from the normal. For example in the diagram below MTHFR 1298C is GT instead of TT. The letters refer to one of the 4 bases that make up the DNA code. If you are getting lost now, then check out the Genetic Science Learning Center below.

The University of Utah Genetic Science Learning Center has an excellent resource that it helps you understand this complex genetic nomenclature and the health significance of these SNPs.

8. What is most affordable way to get MTHFR testing?

Ans. If it is covered by your insurance and that is a big if, that is usually the most affordable way to go, but it requires a physician request. In our office if patients are not in hurry a much better solution is through a genetic testing company.

They offer a much broader profile for $99.00. The only problem is the data is not found in the report. However, two other websites will convert the 23andme data into the form used by physicians for a nominal fee or a donation. Currently, it is taking about two months to get the report back.

We then use Livewello, which charges $20 and you get a nice easy to read color coded report with the data presented using nomenclature familiar to physicians, such as MTHFR 677 rather than rs1801133, which referred to as the rsID. The rsID is useful since many databases use this nomenclature for categorizing information on different genetic snps. See the NIH snp database called dbSNP.

The Livewello data comes in report the looks like this. This is just a small portion of the report. The report is color coded: green means normal, yellow is heterozygous, and red is homozygous. In the second report I have highlighted the MTHFR 677 and MTHFR 1298 snps, which are both yellow, so this individual is compound heterozygous 677/1298. However, you can see from the report that there are other areas of concern.

The table below is the same data copied in spreadsheet format. The links are live and will take you to SNPopedia, which has more detailed information on that SNP.

METHYLATION 3
Gene & Variation	rsID	Risk Allele	Your Alleles	Results
GIF (TCN3)	rs558660	A	AG	+/-
MAO A R297R	rs6323	G	T	-/-
MTHFD1 C105T	rs1076991	T	CT	+/-
MTHFD1 G1958A	rs2236225	A	AG	+/-
MTHFR 03 P39P	rs2066470	A	AG	+/-
MTHFR A1298C	rs1801131	G	GT	+/-
MTHFR A1572G	rs17367504	G	AG	+/-
MTHFR C677T	rs1801133	A	AG	+/-
MTHFR G1793A (R594Q)	rs2274976	T	CT	+/-
MTR A2756G	rs1805087	G	AA	-/-
MTRR A66G	rs1801394	G	AA	-/-
MTRR H595Y	rs10380	T	CT	+/-
MTRR K350A	rs162036	G	AG	+/-
MTRR R415T	rs2287780	T	CC	-/-
MTRR-11 A664A	rs1802059	A	AG	+/-
NOS1	rs3782206	T	CC	-/-
NOS2	rs2297518	A	AG	+/-
NOS2	rs2274894	T	GG	-/-
NOS2	rs2248814	A	GG	-/-
NOS3	rs1800783	A	AT	+/-
NOS3	rs1800779	G	AG	+/-
NOS3	rs3918188	A	AC	+/-