Posted , 6 users are following.
hi there
looking to see if anyone can tell me if you can have hemocromatosis with one gene present on my blood test,my doc says i cant have it but my iron levels are up at 900 and i get a lot of the symptoms discussed on this forum,it all started when i hit 40
1 like, 8 replies
We want the community to be a useful resource for our users but it is important to remember that the community are not moderated or reviewed by doctors and so you should not rely on opinions or advice given by other users in respect of any healthcare matters. Always speak to your doctor before acting and in cases of emergency seek appropriate medical assistance immediately. Use of the community is subject to our Terms of Use and Privacy Policy and steps will be taken to remove posts identified as being in breach of those terms.
KateS71 steven29234
Posted
http://haemochromatosis.org.uk/haemochromatosis/genetics/
Look on here. Hope it explains the genetics better for you
Kate
GillianA KateS71
Posted
Hi Kate,
Unfortunately, although this article uses the term "GH" (meaning "genetic hemochromatosis" ), the description given implies that one gene and one gene only, which isn’t named, causes all types of genetic hemochromatosis. The description gives in the article makes sense for C282Y, mutation of which is the most common cause of genetic hemochromatosis: two normal C282Y genes don’t increase your risk of iron overload, two mutated genes do increase your risk of iron overload, and one mutated gene doesn’t (usually) increase your risk of iron overload, but you can pass it on to your children. What the article doesn’t mention about HFE-related hemochromatosis is that not one, but three, HFE genes have been identified that can be culprits: C282Y, H63D, and S65C. The effects are different depending on which one or which combination of them a person has inherited.
Also, the article doesn't mention any of the non-HFE types of genetic hemochromatosis, which include Juvenile Hemochromatosis (HJV gene or HAMP gene; iron overload tends to show up when people are in their 20’s or 30’s), TfR2-related Hemochromatosis (TfR2 gene – tends to show up in 40’s or 50’s), and Ferroportin Disease (SLC40A1 gene plus maybe others – also tends to show up in 40’s or 50’s).
Bottom line is, this article works for people with mutations of the HFE C282Y gene only. That leaves the rest of us who have other types of mutations bewildered and muttering, “But . . . but . . . if I don’t have two C282Y mutations, then why is my ferritin so high??”
Full disclosure here – the reason I’ve been learning about all this stuff is because I was told by my hematologist that not having a C282Y mutation meant it was highly unlikely that genetic hemochromatosis was causing my high ferritin. Fortunately, while I was waiting to see the hematologist, which took months, another physician had started me on a trial of phlebotomy because I didn’t have any of the usual non-genetic reasons for high ferritin: I had a normal sed rate and C-reactive protein so inflammation wasn’t the problem, I don’t drink much alcohol and my liver and kidneys were working fine, I didn’t have cancer or diabetes or obesity.) My ferritin was coming down nicely with phelbotomies, so my hematologist was willing to continue with them, for which I am very grateful. As it turns out, having 3.5 grams of iron (about 7.5 litres of blood) removed over a year and a half brought my ferritin right down to normal and so far it looks as though a couple of phlebotomies a year will keep it nicely under 50 ug/L. Only C282Y is tested for in Canada, so it took out-of-country private genetic testing for me to find out that I have two HFE-H63D mutations. You’ll see most hemochromatosis sites saying that having two H63D mutations doesn’t cause iron overload, but if you search the medical literature, you’ll find out that’s not always true, as there are reports of people with two H63D mutations and no C282Y mutations who got quite thoroughly iron overloaded. In my case, I suspect that I may have a mutation causing ferroportin loss-of-function type overload, but if so, it’s not one of the SLC40A1 mutations that were tested for as of January 2016. (Mutations that cause problems with ferroportin are still being identified on a regular basis, so who knows, maybe I have a ferroportin-related mutation that’s still waiting to be discovered - )
aj98048 steven29234
Posted
I had differing opinions because I only had the 1 gene. The MRI didn't show much iron deposits and the Gastro doc was like you don't need have it and phlebotomies probably aren't needed. My hematologist disagreed and I did 4 bi-weekly phlebotomies to see how it reacted. I just got my new numbers and my liver enzymes improved dramatically and my ferritin went from 1348 to 229. In my mind just having 1 gene can still increase iron stores but maybe not as dramatically as someone with both genes.
steven29234 aj98048
Posted
marie86421 steven29234
Posted
What gene have you got? You might have 1 copy of C282Y of which you need two copies to load iron. I was negative for C282Y but was loading iron. A genetic test found that I had one copy of H63D and you only need one copy of this to load iron. You might need to get a genetic test done for that, I think it is currently done at Oxford University and your consultant should be able to arrange that.
I hope you get it sorted out.
Marie
steven29234 marie86421
Posted
GillianA steven29234
Posted
You mean one HFE C282Y gene? You usually need two C282Y mutations to get iron overload, but some people with just one C282Y mutation can indeed develop iron overload if other risk factors are present. For example, if you have one C282Y mutation plus a mutation in some other gene that also increases the tendency to iron overload, the combination of the two mutations can lead to excess iron. I believe the most commonly recognized are people who have inherited the combination of one C282Y mutation plus one HFE H63D mutation (often called "compound heterozygotes”); they can and do develop iron overload, although it is usually milder than the iron overload that develops in people with two C282Y mutations.
There are also forms of hemochromatosis caused by having only one of two genes mutated. These are the ferroportin diseases, caused by one of a number of mutations of the SLC40A1 gene - and maybe other genes too - with previously undiscovered SLC40A1 mutations being reported on a regular basis.
(When the mutation of just one gene all by itself causes a disease, that is called autosomal dominant inheritance. When you need two of a gene to be mutated before you get the disease, that is called autosomal recessive inheritance. There are also genetic diseases caused by just one gene being mutated when that gene is found on the X chromosome and not on the Y chromosome; that’s called X-linked inheritance, but as far as I know there aren’t any types of hemochromatosis with X-linked inheritance.)
steven29234 GillianA
Posted
much appreciated