H63D + H63D causing Iron overload

H63D

Gene: HFE

Marker:rs1799945

G

Variant copy from one of your parents



G

Variant copy from your other parent

 Biological explanation

The variant tested is a change from a C to a G in the DNA sequence of the HFE gene. It results in a protein that can't properly control the amount of iron released from cells.

A Iron ferritin test will not show, says normal. It takes the Dr to look at my Hemoglobin and Iron Saturation to obtain results. If iron saturation is greater than 3% and Hemaglobin is greater than 12, a phlebotomy, AR also known as a venIpuncture,, will be done, for those wondering, or researchers interested. 

Phlebotomy is the collection of blood by one of several methods. These methods include: 1) performing a finger puncture with a small lancet to let blood drain from capillaries, which is then collected into a very fine glass tube (capillary tube), a pediatric (microtainer) collection tube, or onto blotter paper; 2) a heel puncture, in lieu of a finger puncture, for neonates and infants; 3) venipuncture; and 4) arteriopuncture or arterial puncture.

Venipuncture, as it relates to phlebotomy, is using a needle to puncture a vein from which to collect blood into a syringe or evacuated tube. (Venipuncture can also be used to introduce into a vein a fluid, such as a medication or a contrast for radiology, but that falls outside the scope of phlebotomy.)

I have only found one other person in ten years, that had done a study of with This rare gene.  Even 23andme DNA, does not say you can be in iron overload.



This is one of the best explanations of how the gene changes a protien, to cause problems.

https://labtestsonline.org/articles/genetic-testing https://labtestsonline.org/articles/genetic-testing

https://labtestsonline.org/genetic-disorders
https://labtestsonline.org/genetic-disorders

https://labtestsonline.org
https://labtestsonline.org

I have been in Anemic Stage since the beginning of January 2019, since doing weekly phlebotomies since October 1, 2018. I have not done any phlebotomy since, as my numbers still are dropping. I emailed my Cancer Center Dr, to make sure I do not get into trouble stage, with such low numbers, along with The phlebotomist center nurses called me, to keep a eye on me.
The only side effect have is I get out of breath, doing simple items. Complete trying to catch my breath, like hiking at 15-20,000 ft elevation. My body not getting enough oxygen, due to new blood my bone marrow is making,  with less oxygen per cell to utilize.

Since this is such a rare blood disease, most doctors do not have a clue, or do not do enough research to find DNA.

 A liver Dr, stood across the room from me, and said there was no possible way I had Hemochromatosis, or iron overload. That I never needed Any phlebotomies. His assistant, who came in before The Dr did, explained some liver test they wanted to do, for uptake of iron from The small intestines to The liver, possibly the cause of The metabolic syndrome going on in my stomach.  The Dr wrote a electronic note to all my other specialists, that said I did not have this


So I spent a day to quote some Items of Yes, I do have Iron Overload. These are the genes involved per my Cancer Center Doctor, and Emailing his quote to all my other Drs.

I was referred to The liver Dr, by my GI Dr, to see iron loading in my system.

Then there was the Gene Dr, for a consultation on the rare gene I have. She quickly dismissed this, and said to send her hemoglobin reports from family members, saying it just ran high with everyone. I did this, and then the format.. My brother supplied 27 pages of hemoglobin reports.


When emailing family,
My siblings stepped in, realizing, this gene was real,  and could be passed down and they did a 23andme test in December, including my mom.  I had The opportunity to see how this gene was being passed down, and think 200 years ago mutated, or unknown. This  just aligned exactly with me and some siblings, others are carriers, who passed The gene to their kids.

I emailed this info to my Gene Dr, as next appointment was a few months away. A email response was thank you. No follow up needed.  The next week was a call of why I cancelled. This brought the Gene Dr to call me personally. I had unanswered questions, and still do, as our three minute talk was not enough about this rare gene, or that I had taken time to find This gene running in my family.

So a full-fledged rollercoaster type of last few months.  The State finally supplied me with a driver and vehicle in January 2019.  I have asked since 2013. Weekly tolls were not nice to our 25 year old cars For the drive, and quite costly, but more On that later.

NORD, National Organization for Rare Diseases,  emailed me about a rare disease and orphan disease convention they are having next weekend in Sacramento. Ensuring a hotel For prior night, as it starts early. So more On this later.

Thanks for reading. If you know of anyone who has thick blood, and these genes line up, would  love to hear.

Thanks for reading
JoeY

Phlebotomy Or Venipuncture number nine

Phlebotomy  venipuncture number nine, with Wil in the background.

For my UK audiences,

Phlebotomy is the collection of blood by one of several methods. These methods include: 1) performing a finger puncture with a small lancet to let blood drain from capillaries, which is then collected into a very fine glass tube (capillary tube), a pediatric (microtainer) collection tube, or onto blotter paper; 2) a heel puncture, in lieu of a finger puncture, for neonates and infants; 3) venipuncture; and 4) arteriopuncture or arterial puncture.

Venipuncture, as it relates to phlebotomy, is using a needle to puncture a vein from which to collect blood into a syringe or evacuated tube. (Venipuncture can also be used to introduce into a vein a fluid, such as a medication or a contrast for radiology, but that falls outside the scope of phlebotomy.)

I've decided to get more technical. Found this video on Facebook, but the actual explanation is done on Brainiac75 YouTube channel

Monster Magnet meets blood
https://m.youtube.com/watch?v=IVsWTkD2M6Qblood

So what can be learned by scientists with this tidbit of information? I'f you are high or low in iron?  Would love comments.


I was interested it HFE is a blood disorder,
 a blood cancer,
or how it is defined, as it will last they test of my life, like Multiple Sclerosis does.

Google answers asking of HFE gene,  provides a spelling
"haemochromatosis an autoimmune disease?
In this severe disorder, iron builds up rapidly in the liver of the developing fetus. It is thought to be an autoimmune disease, in which the body attacks itself. "


A government site shows this
https://ghr.nlm.nih.gov/gene/HFE
The HFE gene provides instructions for producing a protein that is located on the surface of cells, primarily liver and intestinal cells. The HFE protein is also found on some immune system cells.

The HFE protein interacts with other proteins on the cell surface to detect the amount of iron in the body. The HFE protein regulates the production of another protein called hepcidin, which is considered the "master" iron regulatory hormone. Hepcidin is produced by the liver, and it determines how much iron is absorbed from the diet and released from storage sites in the body. When the proteins involved in iron sensing and absorption are functioning properly, iron absorption is tightly regulated. On average, the body absorbs about 10 percent of the iron obtained from the diet.

The HFE protein also interacts with two proteins called transferrin receptors; however, the role of these interactions in iron regulation is unclear.



MEDLINEPLUS SHOWS

Autosomal recessive

Autosomal recessive is one of several ways that a trait, disorder, or disease can be passed down through families.

An autosomal recessive disorder means two copies of an abnormal gene must be present in order for the disease or trait to develop.

Information

Inheriting a specific disease, condition, or trait depends on the type of chromosome that is affected. The two types are autosomal chromosomes and sex chromosomes. It also depends on whether the trait is dominant or recessive.

A mutation in a gene on one of the first 22 nonsex chromosomes can lead to an autosomal disorder.

Genes come in pairs. One gene in each pair comes from the mother, and the other gene comes from the father. Recessive inheritance means both genes in a pair must be abnormal to cause disease. People with only one defective gene in the pair are called carriers. These people are most often not affected with the condition. However, they can pass the abnormal gene to their children.

CHANCES OF INHERITING A TRAIT

If you are born to parents who carry the same autosomal recessive change (mutation), you have a 1 in 4 chance of inheriting the abnormal gene from both parents and developing the disease. You have a 50% (1 in 2) chance of inheriting one abnormal gene. This would make you a carrier.

In other words, for a child born to a couple who both carry the gene (but do not have signs of disease), the expected outcome for each pregnancy is:

A 25% chance that the child is born with two normal genes (normal)A 50% chance that the child is born with one normal and one abnormal gene (carrier, without disease)A 25% chance that the child is born with two abnormal genes (at risk for the disease)

Note: These outcomes do not mean that the children will definitely be carriers or be severely affected.

Yet, another government page shows:

Although a direct association has not been established between HFE mutations and MS susceptibility or clinical outcome 109, a recent retrospective study on patients who were homozygous for HFEC282Y concluded that autoimmune conditions were common among individuals with hemochromatosis

 For technical readers,
Page 18 of https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5569368/  click This link.  This government page
Shows
Autoimmunity

From a different perspective, enhanced immune responses by mutated HFEC282Y may favor the appearance of autoimmunity. Various reports have described autoimmune conditions in association with hemochromatosis. In particular a higher prevalence of the HFEC282Y mutation was observed among cases of multiple sclerosis (MS) and was present among MS patients that had an accelerated onset of the disease and more severe MS symptoms 109, 110, 111. Although a direct association has not been established between HFE mutations and MS susceptibility or clinical outcome 109, a recent retrospective study on patients who were homozygous for HFEC282Y concluded that autoimmune conditions were common among individuals with hemochromatosis 15. Expression of the HFEC282Y mutation could increase the self‐reactivity of CD8+ T cells that cross the blood‐brain barrier, via increased MHC I antigenic presentation. The HFEC282Y mutation may result in an increased presentation of auto‐antigens related to MS beyond a recognition threshold causing the onset and progression of the disease, unlike HFEWT which could inhibit presentation and maintain immunosuppression 109, 111.

The Article goes on to talk about cancers also.

Iron overload is rare in patients homozygous for the H63D mutation
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4071918
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4071918/

Excess Iron and Brain Degeneration: The Little-Known Link
Life extension has interesting info
https://www.lifeextension.com/Magazine/2012/3/Excess-Iron-Brain-Degeneration/Page-01

Suppression of Iron-Regulatory Hepcidin by Vitamin D
Vitamin D and Iron
https://jasn.asnjournals.org/content/25/3/564.full

But mine is just opposite of what article talks about, as I have High Iron. Was on 150,000 iu Vitamin D, to keep my levels up, followed by endocrinologist every three months. I was found initially with vitamin D in Ricketts stage. They phlebotomy has made some drastic changes to my #s increasing, along with my testosterone numbers. Adjustments were made, to my daily regime of meds, and to retest in a month, and again two months later. Such a rare H63d gene, then doctors monitoring, I am keeping notes. Perhaps scientists will look at, as I am quite rare.

Wikipedia defined Hepcidin

Hepcidin synthesis and secretion by the liver is controlled by iron stores within macrophages, inflammation, hypoxia, and erythropoiesis. Macrophages communicate with the hepatocyte to regulate hepcidin release into the circulation via eight different proteins: hemojuvelin, heriditrary hemochromatosis protein, transferrin receptor 2, bone morphogenic protein 6 (BMP6), matriptase-2, neogenin, BMP receptors, and transferrin.^[14]

Erythroferrone, produced in erythroblasts, has been identified as inhibiting hepcidin and so providing more iron for hemoglobin synthesis in situations such as stress erythropoiesis.^[15][16]

Vitamin D has been shown to decrease hepcidin, in cell models looking at transcription and when given in big doses to human volunteers. Optimal function of hepcidin may be predicated upon the adequate presence of vitamin D in the blood.^[17]

I belong to All of Us research program. They sent me a email back questioning the rare H63d Mutation I have

"Indeed, the mutation you have is quite rare so thank you for bringing this to our attention.  I am happy to report that one of the very first actions to be taken by the NIH All of Us Research Program will be to sequence the DNA samples you kindly provided when you allowed us to collect a sample of your blood. This, and any other notable mutations, will be detected by the NIH team and investigators studying this mutation or condition will be notified.

In the meantime, I looked at the list of national clinical trials atClinicalTrials.gov that were studying hemochromatosis. There were about 46 studies listed and a handful currently recruiting in the USA. I am not advocating that you enroll in any, but thought you might like to see what kinds of alternative treatments are being studied for this condition."

 Those interested can contact

Samrrah A. Raouf
Clinical Research Coordinator
All of Us Research Program
UC Davis Health
Office: (916) 734 5772
Mobile (call/text): (916) 502-5605
Allofus@ucdavis.edu
www.joinallofus.org

A update is I have became anemic first of the year 2019, from phlebotomy's. My numbers are still dropping eight weeks later. So no phlebotomy for now, but watching me close, so I do not get to low, as being anemic has its own items, I will talk about in another blog




Thanks for reading
Joey

Ever changing MS

Danger road curves ahead

                                                       Blood phlebotomy from 1800's

A perfect title. Ever Changing Multiple Sclerosis. It is still a very big part of how MS has changed me. I try to be proactive in My approach, learning about the disease, asking universities, and researching a lot of articles, and papers written by the experts.

  My Neurologist told me all the fatigue was MS, has nothing to to do with being in a iron overload state..  Since doing phlebotomy since October 1st of last year, the Cancer Blood Dr. Has had to rely on Hemoglobin numbers, as ferritin numbers showed so different, as if  I was good to go after the second phlebotomy.  The Iron Ratios were still so far off due to the H63d Mutation of the HFE gene. Hemoglobin was the only way to check.  He wanted to get me to a number 10-12,  ferritin >05%. Which would be just Anemic. Being anemic would throw me In a stage of the fatigue caused by being Anemic.  My numbers went down but the MS fatigue never went away.

In the meantime, the Cancer Blood Dr. set me up with a Gene Counsellor.  My GI DR. went and set me up with a liver Dr, due to metabolic syndrome going  on. This was to ensure how much Iron my liver had absorbed by uptake from the small intestines.  I am in between seeing my Neurologist, but keeping them in the loop.  I keep my GO in the loop monthly talking with him.

Not All Doctors are the same. It was a roller coaster day for me and my partner Wil.

The week before I was  undiagnosed with ulcerate colitis. That was good. I was led to believe I had this for two years. VSL#3, prescription strength was used during this time, a mega high dose pro biotic.  I never had The symptoms explained.  My New GI Dr explained this to me.

The Gene Doctor, said I could not have Iron overload, as she scratched some items on paper, showing the feedback loop. I had brought a pamphlet with me, my mom helped put together from Alaska. This was a entire genealogy of relatives, going back generations, and forward to the current generation. Also included was a notebook of any known family diseases, or how a person died, or those living. What was still being worked on was DNA, I let her know.

 Everyone has taken a 23and me a test,but not all results were available, which included mine.  I am sure she had access to doctors notes, that showed he mutations., and lab notes of the H63d gene causing the problem in me, but disregarded them, perhaps undiagnosed me, with her notes, before even seeing me.   She was saying hemoglobin just ran in my family.  This I  checked and emailed to her, after her appointment, showing everyone was normal.  Not sure what she thinks, or I should follow up with her.

 Illustration to show the structure of the DNA double helix.

Image credit: Genome Research Limited.Unravelling-the-double-helix




A interesting article, H63d info, shows the H63d Gene, and since I have two copies mutated, Iron Overload. This gene is also known as

rs1799945

My GI sent me to A liver Dr for metabolic syndrome going on. Perhaps the uptake of iron in the intestines, and stored in organs. His assistant had more yearn for knowledge. He said, perhaps some blood test, so they could check iron uptake into the liver.
It was then, the liver Dr entered the room. Said no way could I have this. I did phlebotomy for nothing, for no reason, undiagnosed me, said he would write notes to all my Dr's, who were wrong. Said I was fine, and left, no follow up needed. I was sitting their with my jaw half open, Wil the unmistakable look of what he just did.

This led me to email my cancer center blood Dr, who ensured me  two mutations of the HFE gene were happening, causing Iron overload, as we discussed.
I spent the rest of the day emailing my cancer center doctors Dr's notes to everyone, and then poof!!!! Liver Dr's notes disappeared, like I never saw him.

Our 25 year old car took a beating, needing many parts, and maintenance for the weekly phlebotomy, and blood test, as Sacramento trips are hard on a old car.  Department of health care service DHCS was supposed to supply transportation during this time, but would not until I sent notes to legal services of northern California,  Lsnc.net and Governor Brown, that they had not since 2013 when asking everyone in the county, and organizations for help.

So not all Drs are created equal, or want to have the knowledge of if they are wrong, or do not know, to come out and say so. A email from either of these two Doctors, would of put some faith back into them.
This led me to a YouTube video I made on the way to a doctor.  caution, Many turns ahead

Danger road curves ahead


Thanks for reading
JoeY