MTHFR is an enzyme , methylenetetrahydrofolate reductase) which is coded for by a gene of the same
name. It has been associated with a
number of conditions in numerous small studies, and widely touted, particularly
in the naturopathic community, as an important cause of ADHD and other mental
disorders. Others feel that MTHFR testing
is just another scam.
How accurate is
testing? How is an abnormal test
defined?
There are many variations of the gene for MTHFR. The important thing to know is that not all
variations cause the MTHFR enzyme to function abnormally. Many are normal
variants which do not affect the health of the individual. When
the enzyme functions at less than 20% of normal, an individual becomes severely
ill, with high levels of homocysteine in the urine, seizures, developmental
delay, and muscular dysfunction, but this is extremely rare, with less than 1%
of the world's population affected.
The genetic variant associated with ADHD is the A1298C variant,
which doesn't do anything to the ability of MTHFR's ability to process folate, produce
methyltetrahydrofolate and or moderate homocysteine levels. Instead it affects the production of
tetrahydrobiopterin, which is needed for production of certain neurotransmitters
(dopamine, serotonin, and norepinephrine included), among other things like
melatonin. This variant is not
associated with heart disease, recurrent pregnancy loss, Alzheimer's disease, neural
tube defects (includes spina bifida) or schizophrenia.
Is there any mutation
specific treatment that can help people with MTHFR variants with their ADHD?
The short answer to this is, for most patients, we don't
know. No studies have been done to show
whether supplementing with any kind of
vitamin or metabolite of a vitamin helps ADHD symptoms in patients with any
MTHFR variant. While it may seem to be
sensible to supplement with methylfolate or BH4, there have been many cases in
medicine where the sensible thing ended up to be detrimental when clinical
studies were done.
In patients who have phenylketonuria (PKU), an uncommon
genetic metabolic disease usually detected on newborn screening, small
trials indicate that treatment with BH4 (drug name: sapropterin) may decrease symptoms of
inattentiveness. However, this could be
due to it lowering levels of phenylalanine, which accumulates in people who
have PKU, but not in people without PKU.
Could treatment be
harmful?
Its hard to believe that increasing one's intake of green,
leafy vegetables could be harmful. If
anything, at least it should help digestion.
However, taking megadoses could be another story.
If a patient takes BH4 (sapropterin), there can be serious
side effects such as bleeding from the stomach and allergic reactions. Hyperactivity can also occur. Headache, runny nose, and diarrhea or
vomitting have been observed commonly with significant replacement doses used
in treating phenylketonuria, a genetic metabolic disease. Because of the way it works, sapropterin can
cause several important drug interactions.
Methylfolate in larger doses may have some mild side effects
as well in some patients, such as agitation, anxiety, irritability, nausea, and
headache, although usually it does not.
It would seem unnecessary to treat the MTHFR A1298C variant
with methylfolate, however, since this variant does not cause problems with the
metabolism of folate.
Is there any harm to
genetic testing?
Yes. While your individual
health information is protected, there is always the possibility that it could
be hacked, leading to a privacy breech.
Many of the services offering genetic test interpretation
are by doctors who do not ever meet you and therefore cannot do as good a job
counseling you as to your test results as a doctor who knows you. This could lead to you making important
medical decisions without the right information. It is important to note that while some
genetic variants have been associated with certain diseases, these are still
only associations. We do not know if
these genetic variations cause these problems or if there are other factors
involved.
Having genetic information about yourself can lead to unpleasant
surprises. When you get tested for MTHFR
variants, you get full genome sequencing, which gives you a lot of other
information. One of the most difficult
issues may be finding out things that you don't want to know--like that you are
not related to your father, or that you are suceptible to a disease that has no
cure.
Finally, having interpreted genetic information could become
a problem if it is required to be released to an insurance provider. While you are protected from certain forms of
discrimination by the Genetics Information Nondiscrimination Act (GINA), the GINA
does not cover life, long term care, or disability insurance.
Bottom line:
Testing for MTHFR does not help us understand or treat a
patient's ADHD at this time because of the lack of proven gene specific
treatments, the risk of treatments that "make metabolic sense", and
because of the inherent risks of genetic testing itself.
References:
"KUVAN® (sapropterin Dihydrochloride) Tablets for Oral
Use and Powder for Oral Solution for PKU." BioMarin : Products : KUVAN®.
BioMarin Pharmaceutical, Inc., 2015. Web. 26 Oct. 2015.
"Methylenetetrahydrofolate Reductase." Wikipedia.
Wikimedia Foundation, 3 Oct. 2015. Web. 26 Oct. 2015.
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