Hereditary Hemochromatosis: Genetics, Mechanisms and More
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- čas přidán 21. 08. 2024
- Are you seeing high iron levels on your blood tests and wondering if you might have hemochromatosis? Maybe you already think you have hemochromatosis and want a little more information about the genetics and some of the things that could be going on in your body? In this video, we look at hemochromatosis, what you need to know about it, how prevalent it is, some of the genetics behind it, and what's actually happening in your body when you have hereditary hemochromatosis.
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Reference links: www.ncbi.nlm.n...
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We're going to look more specifically at hereditary hemochromatosis and why it's important and how it kind of fits into other high iron disorders you might encounter. As mentioned in previous videos, hereditary hemochromatosis is a genetic disorder that is characterized by excessive or increased absorption and accumulation of iron. This genetic condition is very prevalent and it occurs in approximately one in every 200 to one in every 400 individuals. So it's one of the more common genetic disorders. The prevalence is even higher in specific subpopulations like those with Northern European ancestry.
With this condition, you have increased iron absorption from the diet, which leads to accumulation or building up of that iron in your body and specific tissues, which is where the problems come from. So let's talk a little bit about the genetics of hemochromatosis, and then we're going to go into some more of the mechanistic problems or reasons that iron starts to accumulate from this genetic disorder.
From a genetic standpoint, hereditary hemochromatosis occurs or is caused by a mutation in the HFE gene. There are two specific mutations that account for most of hereditary hemochromatosis, and that is a mutation at the C282Y and the H63D. These two mutations will disrupt the normal regulatory process for iron absorption by affecting the interaction of the HFE protein with other proteins involved in the absorption of iron.
So what does this mean? Well, normally, the HFE protein interacts with another protein called the transferrin receptor. That interaction is what is regulating the amount of iron absorbed from the diet. So mutations in the HFE protein lead to an increased iron absorption from the intestines, which results in an accumulation of excess iron in your body, and then eventually into specific tissues like the liver, sometimes joints, pancreas, and other organs.
While we're on the topic of genetics, there are other genetic alterations that can lead to problems with iron metabolism and increased iron absorption. So in particular, mutations in the gene that codes for the protein for hepcidin or also hemojuvelin, both of these are associated with certain types of hemochromatosis.
I wanted to go into a little more detail on what's happening with the HFE protein in hemochromatosis. So, when functioning normally, the HFE protein interacts with the transferrin receptor protein. This interaction helps regulate the absorption of iron by influencing the amount of hepcidin that's being produced.
Normally, the HFE protein binds to the transferrin receptor. Once it's bound, it starts to circulate in the blood. Then, that particular protein can associate with the transferrin molecule that's also bound to iron. This whole complex is thought to be behind what regulates the production of hepcidin.
Hepcidin production happens in the liver, so that whole complex is interacting with the liver and regulating the amount of hepcidin that's being produced. Now, if you remember from the previous video, hepcidin actually reduces the amount of iron absorption that's occurring. So if you have some sort of problem with the HFE protein, you're going to have some abnormal responses either at the place where the HFE protein is binding to the transferrin receptor or the whole complex as it interacts with the transferrin-bound iron. Or as the whole complex interacts with the liver, some part of that chain reaction is getting disrupted and you're getting less hepcidin production from the liver, leading to no regulation of the iron absorption. So it just kind of floats around more freely than it would if the hepcidin was present at normal amounts.
Hepcidin acts like a negative feedback for the absorption of iron coming in through the intestines, but it also reduces or inhibits the release of iron from specific cells that generally store iron, like macrophages and hepatocytes. So, these genetic mutations in the HFE gene, the C282Y and H63D, are altering how well that HFE protein is being produced.
Thank you so much for this information.
Glad it was helpful!
Would like a follow up video looking at the other genetic variants. Non C282Y, but with H63D, S65C, TFR2, etc.
Thank You for this info!
Your welcome
Great video. Is there any link between HFE & MTHFR gene mutation?
No, not that I know of
I'm homozygous H63D. I noticed my iron levels have been increasing but my trf and ferritin are normal. TSAT is 60%.
Do I need to talk to my PCP or continue to watch my levels?
Talk to your doctor
I was diagnosed with hemochromatosis a year ago. I wasn't told which gene mutation I have. I have asked for a nutritionist but they told me really with the mutation your diet doesn't really change the absorption of iron. I was told to not take vitamin c and iron but I want to try and keep my iron low. Do you know of a diet or vitamins and minerals to take or not take? I now donate blood every two months.
Beef, being high in "heme iron," is restricted in diets of those having hereditary Hemachromatosis. Likewise, diminishing Vitamin C, which facilitates iron absorption, is recommended.
What are the antioxidants you suggested in the video? I don't see it in any of the links.
ok they are there now thanks for reminder.
Hello, I have the hematochromatosis H63D, my ferritin was at 500 a year ago and has decreased to 370 now. What are the antioxidant I should take? I started to take NAC and liposomal glutathion, is that enough? I have read that acetyl and propionyl carnitine can help to chelate iron, does it works? Thank you to take time to respond.
Sorry I can’t give that kind of individual advice. I can say that keeping the iron saturation and ferritin in normal ranges as much as possible is the name of the game.
98 μg/dL iron
460.0 ng/mL ferritin
it is suspicion?
Hello from Greece
What about the brain? Does iron accumulate in the brain as well?
That's a great question and yes there is research showing it can accumulate in the brain. although i don't think that is very common but not sure.