Learning About My Risk For Iron Overload

Editor’s note: Pending an FDA decision, 23andMe no longer offers new customers access to health reports referred to in this post. Customers who purchased prior to November 22, 2013 will still be able to see their health reports, but those who purchased after that time will not. Those customers will have access to ancestry information as well as access to their uninterpreted raw data.

Bethann is a Health Content Scientist at 23andMe and regular contributor to the Spittoon. The following is her story about finding out she has a genetic condition that puts her at risk for iron overload.

When I received my 23andMe results my initial reaction was that of relief and curiosity — only slightly increased risk for heart disease, heightened ability to taste bitter food, and slow metabolizer of caffeine. This all seemed reassuring and interesting until I discovered that I’d also inherited two mutations for hereditary hemochromatosis, also known as iron storage disease.

At first I didn’t know what this meant for my health. My particular combination of mutations — one severe C282Y mutation in the HFE gene (a gift from my mother) combined with the much rarer and less severe S65C mutation (courtesy of my father) — only posed a slight risk for developing iron overload. And being a pre-menopausal woman lowered my risk profile even further, because women naturally lose iron through menstruation.

Still, I decided to share the information with my physician to see if follow up testing was warranted. She ordered transferrin saturation and serum ferritin tests, which together provide a good picture of iron absorption and storage in the body, and the results revealed that my transferrin saturation was too high (54%). This result didn’t point to overload per se, but it did prompt me to take a step back and look at my lifestyle.

Hemochromatosis affects an estimated one in every 300 Americans of European ancestry, but many who have it are unaware. Undiagnosed it can quietly lead to iron overload — a serious medical condition. Early detection of the condition is important  knowing your family history and whether you have a genetic risk for iron overload can help you and your doctor decide whether further testing is warranted. Lowering iron levels can be done relatively simply by having blood drawn regularly. Changes in diet can also help maintain safe levels of iron. 

I’d been taking a daily multivitamin with iron for a few months — something I’d only sporadically done in my life — and I promptly stopped taking it. Knowing that I could be absorbing a lot of iron from my uncoated cast iron pan, a family heirloom used for generations in my husband’s family, I moved it to the back shelf. I also decided that it couldn’t hurt to cut back on iron-rich red meat and shellfish and to stop eating iron-fortified cereal for breakfast.

A few months later another iron panel was ordered and I was happy to see that my transferrin saturation had gone down to 25%, a very safe level (on both occasions my serum ferritin was in the normal range). But it wasn’t until I met with a hematologist that I gained a clear understanding of what my genetic results meant for my health.

When I tried to apologize to the hematologist for walking into his office “healthy”, he reassured me that I was doing the right thing and that prevention is key. We discussed my combination of mutations and he advised me to have my transferrin saturation and serum ferritin levels checked every two years. He also said that the game plan could change when I go through menopause and lose my natural way of expelling iron.

My hematologist also confirmed my decision to forgo iron supplementation and agreed that the cast iron pan was probably better off on the back shelf. He did think, however, that I should see how much control I have over the amount of iron I absorb through my diet and suggested that I begin eating some iron-rich food and then get another iron panel. I’m in my thirties and I’d prefer to know now whether my love for  red meat and shellfish is out of the question or if moderate consumption is just fine.

It’s pretty clear that I don’t have much to worry about at the moment since simple lifestyle changes have pushed my iron markers into the healthy range. What has become obvious, though, is that my genetic predisposition for iron overload isn’t just about my health: it’s also about my family. I have two older brothers who could be at risk for hemochromatosis and I’m now in the process of getting them tested. There’s only a 25% chance that each of them also inherited these two mutations, but that’s not a chance that I want to take, especially since simple actions can make a world of difference for those at risk for iron overload.

July is National Hemochromatosis Month. Check out other posts on this condition:
Preventing a Disease Lurking in Her Genome
The Iron Scale: Factors Tipping Towards Overload
• Battling Against A Common Genetic Disease
The Most Common Genetic Disease

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  • Tom

    I see where you mentioned H65C mutation but not the i3002468 T that 23andme mentions in their explanation on hemochromatosis. Did your hematologist have any updates on genes or 23and me about any other mutations? Thanks.

    • BethannH

      Hello Tom,

      Thank you for your comment. The S65C mutation is equivalent to a T at i3002468. In addition to the relatively common C282Y, H63D and S65C mutations, there are at least 17 additional mutations in the HFE gene (all very rare) that are also linked to hemochromatosis. Unfortunately, much less is known about these other mutations since they are all very rare. Just a heads up that 23andMe is in the process of updating its hemochromatosis report to provide results for C282Y, H63D and S65C in the genetic results table of the report. Please reach out if you have more questions.

  • http://spittoon-hemochromatosis SusanA

    I too learned about Hemochromatosis through my Carrier report in 23andme. I was surprised but thought it couldn’t hurt to ask my doctor about it. I had been feeling very tired. I just learned that I am actually iron deficient, at present, because I had cut back on my protein intake-evidently too much. Hopefully I’ll be back to my old self in a couple of weeks.

  • jeff

    Very similar experience. The condition is well controlled just by donating blood frequently. The Red Cross (which once shunned donors w/ hemochromatosis) is very glad to have the donations. A lot has been learned since then.

    I initially gave 12 times in a year to get my iron down to normal and now donate around 4x/yr.

  • http://www.celticcurse.org Stephen Cobb

    Great article Bethann, so glad you found out about your hemochromatosis early.

    Because the iron panel is no longer part of the standard medical checkup in America we are seeing a veritable epidemic of women suffering the ill effects of undiagnosed hemochromatosis as they get older. Excess iron starts to damage joints and organs and although phlebotomy can reduce the iron, much of the damage done is irreversible.

    Over on the Facebook page for Hemochromatosis I frequently recommend 23andMe as a way to find out for yourself if you have the hemochromatosis mutations. The 23andMe service is often less hassle than going through a doctor who might be skeptical or not familiar with HH. And you get so many other results as well, plus the potential for new discoveries from 23andMe research (particularly intriguing in the case of HH which clearly has an ancestral component).

    Thanks for helping to raise awareness of hemchromatosis, a condition you can live with, if you find out early.

    • BethannH

      Hi Stephen,
      Thanks for your kind words and for all that you do to spread awareness about hemochromatosis. I am also very thankful that I found out about my risk for iron overload early. Plus it’s been very easy to make small lifestyle changes that should pay off in the long run. We appreciate you recommending us to your followers and hope that others can also benefit from early detection and treatment. As of July 2012 we now test for three hemochromatosis-causing mutations in the HFE gene: C282Y, H63D, and S65C.

  • Brenlin

    Hi Bethann,

    I guess I’m your opposite. My hemoglobin levels run between 6.5 and 8.5 and my ferritin has tested as low as “two.” (I once tested as only having “trace amounts.”) So I’m totally anemic–and, obviously, don’t have hemochromatosis.

    Nevertheless–I’m wondering if there’s some sort of “spectrum” of metal/iron metabolism, and that someone with hemochromatosis is at one (undesirable) end of the spectrum, while someone like me–anemic for no apparent reason– is at the other (undesirable) end of a metal /iron metabolism spectrum. (Is there something “like” hemochromatosis–but “different?”) :-)

    I don’t know if it is in any way connected, but the one unusual mutation that comes up for me is that I have one copy of the *2A version of the DPYD gene. (Which can give rise to Dihydropyrimidine dehydrogenase deficiency, or DPD.)

    According to Wikipedia:

    “{(DPD deficiency) is } a metabolic disorder in which there is absent or significantly decreased activity of dihydropyrimidine dehydrogenase, an enzyme involved in the metabolism of uracil and thymine.

    (Any chance that this “glitch of metabolism” is related to glitches in iron storage and metabolism?)

    Anyway–was just wondering if anyone had any thoughts on this. I’m a hematologic freak, and all measures to get me (permanently) into normal hemoglobin and ferritin ranges have failed to date.

    But linked below is a good Wikipedia article about human iron metabolism–for anyone interested in the subject.

    http://en.wikipedia.org/wiki/Human_iron_metabolism

    Thanks in advance for any thoughts on my thoughts! (Crazy thoughts welcomed just as much as boring thoughts–I’m officially desperate!) ;-)

    • BethannH

      Hello Brenlin,
      Thank you for your comment. I’m sorry to hear about your chronic anemia. There is some data suggesting that there may be as you say a “spectrum” of iron metabolism. A few studies have been published on common genetic variants that influence iron levels (for instance http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069025/) and it’s theoretically possible that having multiple variants linked to decreased iron absorption could translate to chronic anemia. Regarding hemoglobin specifically, another Spittoon post describes genetic variants located in or near genes involved in regulating iron levels that correlated in at least one study with lower hemoglobin levels (http://spittoon.23andme.com/23andme-research/snpwatch/snpwatch-genetic-variations-influencing-hemoglobin-levels-identified/). Low levels of hemoglobin can also be a sign that something else is going on, though (nutritional deficiency, autoimmune disease or bone marrow problems). As for the *2A variant, although individuals with one copy of this mutation are at increased risk for toxicity from the chemotherapy agent 5-FU, I’m not aware of an association with anemia or iron levels.

      I hope this information is at least somewhat helpful.
      -Bethann

  • Sophia

    Is it possible to be “carrier absent” and still have hemochromatosis? Thanks

    • BethannH

      Hello Sophia,

      It’s a good question. It is theoretically possible to still have hemochromatosis even if your 23andMe results say “carrier absent”. Most forms of hereditary hemochromatosis are caused by mutations in the HFE gene and we provide results for the three most common mutations in this gene. There are, however, at least 17 additional very rare hemochromatosis-causing mutations in the HFE gene that we don’t offer results for. So it’s theoretically possible that someone could have two of these very rare mutations. There are also mutations in a few other genes that cause hemochromatosis, but again these mutations account for only a small minority of all hereditary hemochromatosis cases. There are also forms of hemochromatosis that are not thought to be genetic — some people have developed iron overload purely because of lifestyle, for instance people who get regular blood transfusions can end up absorbing too much iron. I hope this helps. Please reach out if you have more questions.

  • Nancy McGinty

    I see that you got your C282Y from your mother. Does this mutation always come from the mother? We just sent in for a kit to see if my husband is a carrier. If he is then our children can be alerted to be tested.

    • BethannH

      Hi Nancy,

      Thanks for your interest in the post. Children can inherit this mutation from their mother or father. If both you and your husband carry a mutation for hereditary hemochromatosis then your children have a 25% chance of inheriting two mutations (one from each of you) and being born with hereditary hemochromatosis.

  • http://soscience-marcelo.blogspot.com/ Marcelo

    Interesting article. I am a carrier for a predisposing allele but didn’t think much of it until I read about an unexpected consequence of having hemochromatosis: susceptibility to a lab strain of plague. A microbiologist working on a harmless variety of plague bacterium died recently from a plague infection, and it is believed that he had hemochromatosis and that this made him susceptible to this otherwise harmless lab strain of the plague. Ironically, one theory is that this condition would be protective against the dangerous plague bacteria found in nature.

    http://www.dailymail.co.uk/sciencetech/article-1360783/Malcolm-Casadaban-U-S-scientist-die-plague-50-years.html

    Very few people in the world but for a few working in microbiology labs would ever encounter this lab strain of plague, but for those who do work in such labs, genome testing (or better yet, blood tests, in case it’s non-genetic hemochromatosis) might be worthwhile to see if one has this condition. It could save a life.

  • http://HomozygousforC282Y Sherri

    I was diagnosed through blood tests (DNA not available at the time) in 1987, three years after a hysterectomy, and my Serum Ferritn was 2000. I have done phlebotomies since then, at first as often as once a week, but about 1997 my doctor’s noted that my serum ferritin was low. down to 1 at one point, which is very unusual. Then In November 2011 my Hemoglobin dropped to 6.5.so starting in 2012 I received Iron Fusions to bring my serum ferritin up, but it keeps dropping. Try explaining this to a new doctor or even a nurse, that you have iron overload and you are now having a transfusion of iron! Am going to give it a run for the next month taking one iron pill/day to see if I can normalize and maintain. My doctor’s are at a loss for answers.
    Since 1987 I have the DNA test and so have family members. My grandmother was from Scotland on my father’s side and my great grandparents were Irish on my mother’s side.
    Dad is homozygous C282Y
    Mom is heterozygous (I think)
    Sister is homozygous C282Y
    Sister is heterozygous (I think)
    Daughters are compound heterozygous C282Y/H63D
    My uncle (Homozygous C282Y) was the first to be diagnosed and that saved my life. You can’t imagine what it took to convince the doctor to test me in 1987! My uncle often needed two phlebotimies a week.
    My sister who is a lab technician told me with the iron overload I would be resistant to the yellow plague which I have no documentation to confirm that.
    Many years on public radio I heard the Kaiser Permanente (KP) made the blood tests part of a regular blood panel because the cost of the tests was so small compared the costs later on (e.g. liver transplant). My parents just the other day said KP called to get permission to run more genetic tests from their blood samples.
    Hang in there!
    ~ Sherri

    • BethannH

      Hi Sherri,
      Thank you for sharing your story. I sincerely hope that your ferritin levels stabilize and that the rest of your family members are also able to manage their hemochromatosis. Thank you also for the information about Kaiser Permanente screening for hemochromatosis — very interesting!
      Best,
      Bethann

      • Åsa

        I think it depends on what Kaiser facility you are using and who your primary care physician is whether hemochromatosis screening is easily obtained.

        My brother-in-law was 60 years old when he died from previously undiagnosed hemochromatosis a couple of years ago. Fortunately, it was determined before he died that hemochromatosis was the reason his organs were shutting down. My husband and another brother were diagnosed right away and started aggressive phlebotomy, which has brought their ferritin levels down to normal.

        Obviously, I wanted my son tested for the genes since he was guaranteed to at least be a carrier of C282Y – especially since I’m Swedish and thus would be more likely than the general population to be a hemochromatosis carrier. My son was under 18 at the time and the genetics department would under no circumstances test him before he turned 18. After my son turned 18, the Kaiser genetics department would still not approve a genetic test, telling us that his ferritin levels should instead be monitored with blood tests. In my opinion, this is an insane approach when you know you might be at risk and could take a lot of steps to prevent ferritin levels to go up in the first place. Fortunately, my son’s primary care physician overrode the genetics department’s decision and sent him to be tested. My son turned out the be homozygous for C282Y – invaluable information in my opinion!

        Now that I know that I am at least a carrier, I’m trying to get a genetic test for myself through Kaiser. This has turned out to be even more difficult than getting my son tested since both the genetics department and my PCP don’t think that testing is necessary. I may just go ahead and use your services instead. It feels very humiliating to be dismissed over and over again.

  • Ansarac

    I recuperate from demanding, physical activity, by eating iron rich foods, so question whether sedentary people would be most affected by iron overload.

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