Question 1: I read that if you’re Heterozygous, that means you are a ‘carrier’ and may pass the gene on to your offspring. That implies to me that a carrier would not suffer from high iron levels. Is this correct, or is there still some impact? I don’t understand the dominance relating to this gene - is the correct gene completely dominant, the incorrect gene completely dominant, or do both copies of the gene contribute 50/50, so you’d suffer from high iron but not as badly as a homozygous person?
Question 2: When untreated, do iron levels increase reasonably consistently or can they fluctuate widely? Could someone have very high levels of iron, suffer symptoms unknowingly, then a year later get tested and only have moderately high levels? (without having any blood loss or donations in the intervening year). Or do iron levels really only go up? (again, in the absence of blood donations, etc)
There are some other tests that can indicate the disorder (such as testing the blood’s iron levels) that don’t involve genetic testing as well. This is less of a concern as the cost of genetic testing keeps coming down.
The truth is the disease is not completely understood by anyone at this point. Also, I’m not a doctor or research scientist, just a well-read geek. Nonetheless, that seems to be the case - carriers don’t seem adversely affected.
The body doesn’t really have a good way to get rid of excess iron. Absent bleeding, yeah, iron levels go up. Now, if, hypothetically, you had someone go on a diet with little to no iron in it for a year their levels might start to fall as the body uses the iron already on board but that’s unlikely to happen in normal Western civilization.
Incidentally, regular blood loss in the form of menstruation keeps women with this disease healthier for several decades longer than their male counterparts. Menstruation isn’t a heck of a lot of blood, so really it doesn’t take that much to bring down iron levels and then maintain them… but you have to know its necessary. One reason these genes might have survived in the population was because having the condition is actually protective for a woman in a low-iron environment/diet which might have prevailed at one time in the part of Europe where this trait is most prevalent. Or maybe not, it’s just a WAG.
Bottom line, though - if you suspect you might have this gene variant you should get tested as early as possible and start those regular bleedings BEFORE major organ damage occurs (earlier this month I lost an internet friend to the end stage of hemachromatosis).
I used to do the genetic testing for hereditary hemochromatosis (there’s also a non-genetic version).
There are two specific mutations within the HFE gene that are known to increase the risk of hemochromatosis. There’s a third that is questionable. Having one mutated copy of the gene (heterozygous) slightly increases your iron levels, but you’re very unlikely to ever develop symptoms of the disease. It is therefore considered a recessive disease, though that terminology is falling out of favor as we learn more and more about the details of molecular biology.
As for question 2, iron levels are controlled almost completely by the uptake system. So how much iron you eat will determine how much iron is in your blood. You lose some at a constant rate as old red blood cells are removed in your poop. If you’re female, you also lose some every month during menstruation. This is why it’s most often seen as a disease of men.
If you’re interested, the HFE gene encodes a protein that lives on the cell surface and detects iron levels in the blood. When it binds to an iron-bound protein, it sends a signal to the iron uptake proteins saying, in essence, “we have enough iron! Stop taking up more!” The mutation prevents this protein from binding to another small protein called beta-2 microglobin, which acts sort of like a postage stamp in the cell. Without binding B-2, the HFE protein never makes it to the cell surface, and so the overall “we have enough iron!” signal is reduced. Therefore, the gut cells constantly thing you’re short of iron and is constantly trying to absorb more and more.
Over a great deal of time, the excess iron can build up to dangerous levels in the body and start damaging tissue, leading eventually to liver and heart damage (most often). Unfortunately, by the time symptoms develop, usually in middle age, the damage is often irreversible. On the other hand, if you know you have the mutation, it’s very easy to treat with a low-iron diet (avoid steaks) and, somewhat amusingly, bloodletting. They just take out blood until your iron levels get back to normal.
About thirty percent of previously undetected homozygotes will already have established disease when they are first discovered in the course of family screening (undertaken because of the presence of a homozygote and symptomatic family member).
As I understand it (and as a very brief look through ‘the literature’ seems to confirm), it is still a matter of some controversy whether heterozygotes are at increased risk for disease.
Thank you Broomstick, Smeghead & KarlGauss!
Very informative answers.
(and yeah, I do have high iron levels, got the genetic test done and it came back positive. I’m trying to learn more about the condition in general before my next appointment with the doctor, so I have more understanding and can ask more specific questions about my situation - so many thanks for clearing up some of my misunderstanding and confusion)
I may bump this thread if more questions occur to me!
I don’t think there’s actually any such thing as true complete dominance, for any gene. Saying that a gene is dominant or recessive is just shorthand for saying that the effects of being heterozygous are very small, compared to the effects of being homozygous “dominant”.
And while being heterozygous for hemochromatosis does tend to result in higher iron levels, there are enough other sources of variability that it’s not a sure thing. Both of my parents must have been carriers, since I have the condition, but both of them have actually had chronically low iron levels (even after menopause, in Mom’s case). This was, in fact, one of the reasons that I suspected I didn’t have it, until the genetic test came back.
I’ve gotta say, too, that as genetic diseases go, hemochromatosis is probably about the best one to have. It’s easy to diagnose (if anyone even thinks to look for it-- I’m not sure what the current status is there), and once diagnosed, it’s really easy to treat, too, with few side effects.