GH - Homozygous H63D gene mutation - memory problems

[Greenman222]

3 years ago I was diagnosed with 2x H63D gene mutation. This has proved to be a blessing and a curse. As all my life I’ve had memory problems. This has affected all aspects of daily life. The main one being my education. I left school with nothing and for the next forty years. I’ve struggled to hold down jobs. So when I found out that the 2x H63D affects your memory. It was like a weight lifted. But the next hurdle is, do I want to know is E4/E4? The answer is yes, as I want to know. As I have a bucket list of things I want to do. Before the little grey cells give out. Anyone feeling the same?

[NF52]

3 years ago I was diagnosed with 2x H63D gene mutation. This has proved to be a blessing and a curse. As all my life I’ve had memory problems. This has affected all aspects of daily life. The main one being my education. I left school with nothing and for the next forty years. I’ve struggled to hold down jobs. So when I found out that the 2x H63D affects your memory. It was like a weight lifted. But the next hurdle is, do I want to know is E4/E4? The answer is yes, as I want to know. As I have a bucket list of things I want to do. Before the little grey cells give out. Anyone feeling the same?

Welcome, Greenman222,

I have a sister whose doctor has told her she has familial hemachromatosis, although I don't know which of the two common genetic variants she may carry. Her only "treatment" is to donate blood about 3 times a year. I do not carry either of those variants, so am curious about your feeling that is has proved to be a "blessing and a curse". Can you share the sources for that? Or is it your belief that this must be the explanation for your struggles in school and in jobs?

If so, I want to offer my deepest apologies on behalf of all educators. I was a H.S. English teacher in the 1970's for 4 years before deciding that I needed to learn more about learning disabilities. I knew I was failing the students in my classes who hated reading, writing and tests. What I learned in grad school and over many years with wonderful kids is that memory is incredibly complex:

• We have long-term memories of emotion-filled episodes that last for decades.
  We short-term memories of what we had for breakfast that may be gone in 48 hours or less.
  We have "prospective memories" for what we have to do in the future (when my daughter comes over, I have to ask her about our grandson's birthday)
  And working memories for information we hold onto for a minute or less (like what we came into a room to get).
  We all have tons of procedural memories of how to do things that use our muscles and visual cues, and even people coming out of comas may hold a baseball correctly if it's a strong memory.
  We have semantic or category memories (letters, number facts, animals, names of sports team or favorite movies or fruits or musical instruments or the Yankees line-ups for the last 40 years.)

And yet all of us tend to say "I have a good memory" or "I have a bad memory" as if memory were only that thing that we do well or poorly. The truth is, I can look really smart if you ask me to spell a word, and really not smart if you ask me the name of the Star Trek movies.

Today we have WAY more skills to use to teach kids whose learning style isn't "typical". So while I am sorry for the struggles you've had, I hope you realize your brain is still able to learn at 58 or 68 or 78 or 88--if given the right tools.

And as far as H63D, I searched Google Scholar for articles on H63D and memory disorders and only found a few that were more than a dozen years old, which raises a red flag for me. This article from 2014 suggests that you may not have too much to worry about:

In summary, the use of H63D genotyping has created a new subgroup of patients (H63D homozygotes, C282Y/H63D compound heterozygotes) that have rarely had any illness associated with iron overload. In many ways, these are genotypes searching for an illness. The movement to drop the H63D genetic test from routine HFE genotyping has not gained ground because of the low cost and the quest for new information (Box 1). In my own practice, I suggest voluntary blood donation two to three times per year for concerned patients, and rarely institute weekly phlebotomy. The health benefits appear to be minimal, other than increasing the blood donor pool, which should be encouraged.

[Emphasis added.] H63D genotyping for hemochromatosis: Helper or hindrance?

By all means have that bucket list and figure out ways to have experiences and purpose and a sense of giving back and making things and feeling a sense of accomplishment. And before you test for ApoE4, maybe read this: Thinking about Testing?

"How-To" Get the most out of the ApoE4.info website may help you "search" for topics, "quote" members so they get a notification of your post, and "subscribe" to this conversation so you get notified of any new posts.

We value all of our brains--and believe we all contain amazing abilities.

[Greenman222]

Information about the H63D mutation

Mutations of the hemochromato- sis gene HFe have been associated with liver disease, bone and joint disease, diabetes mellitus, heart disease, hormone imbalances, porphyria cutanea tarda (PCT), infertility, stroke, neurodegen- erative disorders, cancer, venous and peripheral artery disease.
In the years since discovery of HFe and its mutations, research- ers have focused studies primarily on the C282Y mutation because of its prominence in people with elevated iron levels. About 85% of individuals with abnormally high iron possess two copies of C282Y, therefore this mutation has been more extensively studied. Other mutations such as S65C or H63D have not garnered the attention of researchers. The S65C muta-
tion may lead to mild to moder- ate hepatic (liver) iron overload, especially when in combination with other mutations. C282Y/ S65C compound heterozygotes have demonstrated elevated se- rum iron indices and iron over- load.
When examined, H63D stands out as a significant modifier of disease onset, progression and even response to therapy. H63D is associated with arterial stiff- ness, pro-oxidation, higher to- tal and low-density lipoprotein cholesterol when alcohol is con- sumed; acute lymphoblastic leu- kemia (ALL); decreased sperm production; higher risk of type II diabetes mellitus. Being a carrier of the H63D hemochromatosis mutation is a risk factor for ear- lier onset and longer duration of kidney disease in type II diabetic patients.
Alcoholic liver disease is more prominent in the H63D homo- zygote. Being a carrier (hetero- zygote) of H63D mutation is associated with a higher risk of liver cancer in cirrhotic patients regardless of their underlying liver disease. H63D was present in 42% of in patients with alpha- 1-antitrypsin deficiency who had cirrhosis. H63D mutation was an independent factor associat- ed with viral response to therapy for chronic hepatitis C patients.
The most striking risk associated with H63D is for the neurode- generative diseases. Connor, et al were among the first investigators to consider the role of H63D in brain iron accumulation, oxida- tive stress and neurotransmitter performance. Connor reported that the H63D HFE variant con- tributes to many of the process- es associated with Alzheimer’s Disease (AD). These processes include increased cellular iron, oxidative stress (free radical ac- tivity), glutamate dyshomeosta- sis (abnormal balance), and an increase in tau phosphorylation (abnormal levels of tau proteins can result in dementias such as Alzheimer’s).
Connor continues that HFE H63D cells were shown to have more oxidative stress, further support- ing their role as neurodegenera- tive disease modifiers. Connor found that patients homozygous for H63D had earlier signs of mild cognitive impairment and earlier onset of Alzheimer’s com- pared to those with normal HFe or H63D heterozygotes.

[Greenman222]

Homozygous H63D Haemochromatosis ~ It’s more than just iron overload! This is what I promote. Most if not all GH societies just focus on the the iron. But the most striking risk is the link to Alzheimer’s and memory problems. The H63D is indeed very common. 1 in 5 White Europeans are carriers and 1 in 100 carry two copies. I’m awaiting to be tested for the APOe4. As I want to know my level of risk. I have a bucket list and I want to make memories now.

[Greenman222]

The Homozygous H63D also carries a triple risk of strokes in the brain.