Carrier with C282Y Gene & High Ferritin

Thank you she sees the hematologist tomorrow and hopefully will know more.

Thanks for asking but am not sure that the proper information was given.  First he didn't seem concerned with the level of her ferritin, and dismissed inflammation or infection causing the increase in the level.  Knowing I had HH he suggested that I get a liver scan.  He told her to donate blood every 8 weeks and see him in 8 months. I then interestingly enough he said when you go to donate don't tell them you have Haemochromatosis.  This is another reason of concern from this Dr.s appointment.  I asked my Dr. and she indicated that with one gene there is no chance of having HH.  She lives in another state and would like her to see her gastro Dr. to see if he will have the same take on this elevation.  We will be seeing her next week and I will be suggesting she seek another opinion.  

There are many reasons why a ferritin level can increase other than having HH.  It does not take much to do a CRP test for inflammation/infection levels to eliminate that possibility.  An Iron Studies blood test is a window to a lot of health issues.  So pressure needs to be put on the dr to follow through.

Fatty liver is the most common problem.  This is caused by consumption of sugars and starches, and alcohol.

He was right to say not to mention HH when donating blood.  First, she has not been diagnosed with HH, and Second, she will be sent away and it will be on her blood donor record which will prevent her donating blood anywhere unless a dr has ordered it for therapeutic reasons.

Donating blood will not cure the cause of the increased ferritin level, when it is not HH, but may help alleviate some problems as donating blood is generally good for all of us.

The recommendation to see a gastro dr should be followed through as it may provide the answer to her health issues.

 

Thank you Sheryl for your response. I certainly agree that she was dismissed without getting down to the bottom of the situation.  She continues to be extremely exhausted and tired and has sought advice from her GP which has also gone nowhere  She is treated by her gastro Dr for IBS so thought she might get a better response from him.  

Vit B12 and Vit D is VERY important and deficiency in these can cause same problems.  I think I have mentioned that Vit B12 in injection form is the way to go because some of us don't absorb it in the tablet form.  Same with Vit D, a practitioners brand of Vit D3 drops actually work compared to tablet form.

 

Thanks again for this additional information  I will be seeing her tomorrow and try to encourage her to get to the bottom of these symptoms

Thanks for this info - I will try to contact Sheryl

Google "Can heterozygous C282Y get haemochromatosis?" and see what you get.  No confirmation whatsoever.  I have asked HH researchers about it.  No, negative, etc.  It would seem that your gastroenterologist does not understand genetic haemochromatosis.  People with or without a genetic HFE gene can get a ferritin overload for OTHER reasons.  It is quite common.

The cause of this needs to be investigated properly and not just allocated to the haemochromatosis basket.  Unless you have true haemochromatosis your monthly donation would have made you feel worse.  It sounds like your gastroenterologist is not advocating monthly venesections but will be monitoring.

You can donate 3 monthly and it would probably make you feel good for a while but it won't cure the cause, which is what you need to urge your drs to search for.

 

I am a female C282Y carrier with symptoms.  My bone marrow biopsy shows elevated iron, my ferritin is slightly elevated in the 300s, my hematocrit is between 48-51 and my hemoglobin is between 17-19.  I have symptoms of itchy skin, fatigue, muscle cramping and aches and tingling in my feet/hands.  I’ve managed with phlebotomies for 30 years.  I was originally misdiagnosed with polycythemia many years ago, but now that genetic testing exist I’m know I’m at least a carrier of C282Y (maybe there are genes that aren’t yet identified).    

It is quite possible there are other genes that aren't yet identified.  The one that is sometimes tested for is S65C is so harmless it basically does not count.  Any others to yet appear will be the same or less.  The aggressive ones would be more obvious.

They are searching for a gene that makes some people with homozygous C282Y more aggressively load iron than others who are homozygous but don't load iron at all.

How often did you have phlebotomies when you were diagnosed?  Were you able to have weekly phlebs?  How often are you having phlebs now?

If you are still having these symptoms almost 30 years of venesections (and supposedly de-ironed) then something else is wrong which is causing your elevated ferritin. If your ferritin level is currently 300 then you have not been de-ironed and kept there.  I keep mine about 34 and less with 3 monthly maintenance phlebs and I have been doing that for years now.

Non HH people can sustain 3 monthly donations.  You might be doing yourself a favour by pushing for an appropriate diagnosis for your health issues.

Good luck.

 

I have your exact same symptoms as you; it is a result of being C282Y carrier with symptoms. I had genetic HH DNA test that was quite extensive. Finally researcher from Mayos and Director of Gastro with extensive research in HH as I mentioned before said C282Y is only gene that can have symptoms as a carrier. That combined with premature deaths of family members has given me lots of answers. I have also lost parathyroid glands, thyroid glands and pituitary glands due to iron overload. There is a correlation between iron overload and losing those glands documented in the research.

This disease is not cookie cutter and I would advocate after much trial and error to find physicians with HH expertise and not other bloggers.

My physicians are responsible for my longevity as they treat me as an individual not a disease. My symptoms are now manageable. I am hoping not to lose adrenal. I have felt much better not doing monthly phlebotomies, but on an as needed basis. 

best

 

m.65177 is right in advising you to seek official medical advice rather than just from forums.  I am amazed at the number of people who come here first before reading medical research and educating themselves about haemochromatosis.  Without this knowledge you would not know if you have found a good knowledgeable dr who has read up on research or someone with their own brand of beliefs.

I searched for research under the umbrella of the Mayo Clinic and found none related to confirming heterozygous C282Y loading iron under HH conditions.  Perhaps m.65177's dr has not published.  If he did, it would be significant in the HH world of researchers.

However, I had forgotten about the disorder of ferroportin which is different to the classic haemochromatosis and needs to be treated differently.  There is a poster on this forum who has had to find out all about ferroportin herself and she says Canada (where she comes from) do not test for it.  I must say it does not come up in Australia nor at the conferences I have attended with the best HH and most prolific researchers and publishers around the world as keynote speakers.

Check out previous haemochromatosis posts to find her posts regarding this disorder and you might find some similarities (or not!).  It is not something I have made myself familiar with because it is rarely diagnosed.  In this case only one gene is required to set it off.  That might explain why you still have these problems and high ferritin levels after 30 years of regular phlebotomies because it is difficult to treat.

When seeking information about hemochrombtosis, everyone should quote all their Iron Studies results because all this information is relevant and important to hemochromatosis.  Hb and hematocrit not so.  Although it is good to have a high Hb in order to withstand multiple and close scheduling of phlebotomies.

Good luck and let us know how you go.

 

Thanks again for sharing your knowledge of this condition as many Drs are not familiar with the condition which makes this forum helpful when you don't seem to get the answers you need from the Dr.  It is a a very complicated condition and when each person is different doesn't help to explain things either   

Please review:

Aguilar-Martinez, P., Grandchamp, B., Cunat, S., Cadet, E., Blanc, F., Nourrit, M., … Rochette, J. (2011). Iron overload in HFE C282Y heterozygotes at first genetic testing: a strategy for identifying rare HFE variants. Haematologica, 96(4), 507–514. http://doi.org/10.3324/haematol.2010.029751

"Conclusions

Our results suggest that additional mutations in HFE may have a clinical impact in C282Y carriers. In conjunction with results from previously described cases we conclude that an elevated transferrin saturation level and elevated hepatic iron index should indicate the utility of searching for further HFEmutations in C282Y heterozygotes prior to other iron gene studies."

Please review:

http://www.irondisorders.org/classic-hemochromatosis

"HFE, the gene for classic hemochromatosis, was discovered by a team of scientists in California 1996. Two major mutations of HFE attributable to iron loading are C282Y and H63D. Numerous prevalence studies support that the C282Y mutation of HFE is common among whites. In this population, one in 200-250 are homozygous (have two mutated copies). One in 50 are compound heterozygotes (have one C282Y mutation and one H63D mutation). One in 8-10 are simple heterozygotes or carriers of one C282Y mutation."

"One’s family history of disease can offer clues that hemochromatosis may be present. A simple iron panel should be performed on anyone with a family history of any of the following:

•    a premature death by heart attack or liver cancer

•    diabetes mellitus

•    skin color changes—bronze colored skin (year-round tan without being in the sun)

•    osteoarthritis or complaint of pain the first two knuckles of the hands (iron fist)osteoporosis (especially joint replacement)

•    hypothyroidism

•    infertility

•    impotence or depression

Sufficient evidence warrants routine monitoring iron levels in heterozygotes (carriers), especially when there is a family history of disease."

"MOST AT RISK

C282Y homozygote and the C282Y/H63D compound heterozygote

MODERATE RISK 

H63D homozygote or other compound heterozygote combinations

LOW RISK

C282Y heterozygote (carrier); H63D heterozygote (carrier) or S65C heterozygote (carrier)"

Please review:

Beaton, M. D., & Adams, P. C. (2007). The myths and realities of hemochromatosis. Canadian Journal of Gastroenterology, 21(2), 101–104.

"Carriers of the hemochromatosis gene often have iron overload

It has been common for physicians to tell patients with mild elevations in serum ferritin levels that they may be carriers of the hemochromatosis gene. Mild elevations in serum ferritin levels in the general population are very common and occur in all ethnic groups, so they are unlikely to be explained on the basis of heterozygosity for the hemochromatosis gene. A large population study (1) has now demonstrated that C282Y heterozygotes have iron studies similar to those of the general population. There is an increased prevalence of mild iron overload in compound heterozygotes (C282Y/H63D), and some C282Y heterozygotes may also carry an unidentified second mutation."

Please review:

http://www.genetics.edu.au/publications-and-resources/facts-sheets/fact-sheet-47-hereditary-haemochromatosis

"Approximately 0.5-2% of people with one copy of the C282Y mutation and one copy of the H63D mutation will have iron overload "

Please review:

http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hemochromatosis/

There are many more research articles and websites describing C282Y single gene. I invite you to continue your journey of knowledge. 

Best

Thank you so much for your links regarding this issue.  I had already read the first Aguilar-Martinez et al. and queried it with a HH researcher.  His answer was that the study involved too small a number of participants to be taken as definitive, and the word "may" covers the team's bases.  Either way it was deemed so rare that it was highly recommended that people who are heterozygous C282Y and have these symptoms to have other causes investigated for their sake of their health and not rely of the diagnosis of haemochromatosis.

A database of people with hemochromatosis in France (well, the southern half it seems) is kept in Montpellier.  These 6 people being the only ones in question out of the database and were referred to the Aguilar-Martinez et al study - two x 2 being brothers.  The only female patient in this series bore a mutation (p.Leu183Pro) previously described in two unrelated Dutch probands.  The researchers are wondering if these 3 had the same haplotype - there was no known kindred relationship.  Wouldn't it be good if all our countries kept a data base too?  I am sure much more information would be achieved and made available.

This research team also recommended that other causes for iron overload be investigated.

I have personally talked to very many people in my city who have been told they have haemochromatosis when they were heterozygous.  In fact, more than had been genetically tested homozygous.  If all these people and those on this forum do have as yet unidentified haemochromatosis genes, then it is not so rare as indicated.

Of course, it is very important to have iron overload for any reason be investigated and monitored, and it is beneficial for most people to donate blood.

Re Iron Disorders Institute, when I read the page, my 'copy' does not say:

"MOST AT RISK

C282Y homozygote and the C282Y/H63D compound heterozygote

MODERATE RISK 

H63D homozygote or other compound heterozygote combinations

LOW RISK

C282Y heterozygote (carrier); H63D heterozygote (carrier) or S65C heterozygote (carrier)"

(Anyone heard of anyone who are homozygous S65C?  What about those?)

I have not referred to the Iron Disorders Institute for a long while and it is not something I had seen Iron Disorders Institute publish.  Did you read the "Iron Overload" page?  The list of symptoms caused by other factors was pretty much the same as HH.

Prof Paul Adams, a researcher to whom I have spoken about a couple of years ago, also says " A large population study (1) has now demonstrated that C282Y heterozygotes have iron studies similar to those of the general population."  The large population study involved 99,711 participants. His statement " some C282Y heterozygotes may also carry an unidentified second mutation." seems contradictory of what he had said in the same paragraph.  The article was about myths and realities, so I am not sure what he is meaning there.  There is that word "may" again.  It is like an afterthought. He has expressed to me and in his key note addresses very definite views on haemochromatosis.  He generally does not 'cover his bases'.  I have not come across any research by Prof Paul Adams which proves this.

I am not sure what you are saying about compound heterozygous C282Y/H63D.  It is a proven fact and has been for years.  My son is compound heterozygous C282Y/H63D and had a high ferritin level (772) at age 22, and my husband is homozygous H63D and had a ferritin level of 554 at age 50.  After some venesections and Hodgkin's Lymphoma with a treatment of chemo and radium therapy he no longer loads iron, but this was likely to happen anyway with H63D.  He seemed to be asymptomatic before he was diagnosed.  My son had glandular fever at age 18 which caused some damage to a lot of the organs that are affected by HH and this may have had an impact on his levels at such a young age.

Hopefully this spectrum will be explored and researched further with many more participants instead of it being a possibility (or a 'may' for a rare number of people.  Currently, it is only the Aguilar-Martinez team that has actually researched it and with a very small number of participants.

I think it will be, as the debate about what exactly defines a hemochromatotic is suggested to be explored at the next HH scientific conference.

So the outcome will be very interesting to a lot of people.

 

Sorry for the slow response-I just saw your question.  When I was initially diagnosed with polycythemia many years ago, the doctor’s only concerned was lowering my hematocrit to 47 or below to alleviate symptoms and little thought was given to my ferritin level.  I managed my hematocrit level until six years ago when my adult daughter passed away from sudden cardiac death-she also had elevated blood levels..

At that time, I went to a University of Kansas doctor who, after a lot of testing, said I didn’t have polycythemia and I just naturally have high hematocrit and hemoglobin levels and I needed no further treatment (which in retrospect, the bone marrow biopsy he did showed elevated iron so I’m not sure why I was released from treatment.)

I had no further treatment for five years, but this summer I did the 23 and me test which does show I’m a C282y carrier.  Over the past five years my symptoms have gradually worsened so this fall I made an appointment to see the hematologist and he did again start treatment.  I’ve had five phlebotomy’s in ten weeks and my current ferritin level is 27.  I feel so much better and I haven’t had leg cramps since October.  I see the hematologist again in February.  My phlebotomy’s did little to change my high hematocrit and hemoglobin although the have come down slightly.  

I should add that my Very Long Chain Fatty Acids are elevated enough that I had genetic testing for carrier status of adrenoleukodystrophy but I’m clear.  I wonder it there is a connection between hemochromatosis and elevated VLCFAs?  Scientists know very little about VLCFAs.

I think everyone has a different story to tell and thats whats so difficult to understand  It doesnt seem any Drs are on the same page  Probably not enough studies