Copper deficiency induced bone marrow failure

[Chirley]

Hi,

I've decided to cease posting in my other thread and to start this one instead because the thread title is more pertinent.

My story so far.

Low WCC noted in 2003 when being treated for severe pneumonia. Later in 2003 found to be anaemic. Received first blood transfusion. Diagnosed with Fe deficiency anaemia. Numerous investigations including BMBs.

Progressive anaemia which became transfusion dependent and BMBs started showing abnormalities along with Fe deficiency. I was told ? Evolving MDS.

WCC started showing severe neutropenia. Finally in early 2010 BMB showed
definite MDS RCMD. Started Vidaza. Repeat BMB after 3 cycles showed increasing blasts. Now, MDS RAEB. 1.

In the meantime I had started experiencing neuropathic pain in my feet and legs and electric shocks in my arms when I bent my neck. This was thought
to be Vidaza related. The neuro symptoms progressed and I started having trouble with balance and eventually had difficulty walking. MRI showed cervical demyelination of the spinal cord. CSF showed increased protein and
the presence of an abnormal protein called 14-3-3. After 2 further cycles of Vidaza it was ceased in case it was the cause and because BMB showed blasts had increased again.

Finally after numerous tests i was found to be copper deficient. By this stage I had cerebellar degeneration and cervical and thoracic demyelination and couldn't walk without assistance.

It has been established that I have a genetic abnormality of the copper transport proteins which prevents absorption of copper from the gut and also
inability of the kidneys to retain copper in the blood. Hence treatment by copper replacement is a chase your tail proposition. No matter how much copper is given intravenously, it will always be excreted.

So far I have had copper replacement in the form of oral copper sulfate (no effect), subcutaneous injections of copper histidine (which did work but were painful and caused aseptic abcesses) and now, ongoing intravenous copper
sulfate.

My bone marrow failure has resolved with just occassional CBC abnormalities and my neurological progression has slowed considerably but I'm not convinced that disease progression has stopped.

Regards

Chirley

[cathybee1]

Chirley, I'm so glad you posted this. This has been such a long journey for you. In reading this, I realized I have yet another question for you. Which copper transport protein is not working properly, and how did they determine it?

[Chirley]

Hi Catherine, that's a good question.

I asked the Prof the same thing. They don't know how many transport proteins there are let alone how they work or what other interactions they have.

That's part of the reason I became a bit down after my visit to him. He said that just because the blood copper levels are normal it doesn't mean the copper is being utilized in all the necessary places. There may be a transport protein missing that stops the copper from being utilized at cellular level.

Then I read an article about a man who had copper deficiency who didn't respond to copper replacement and ended up having brain stem involvement. He became blind and wheelchair bound despite treatment.

There is so little known about copper and it's metabolism that when i read an article like that, i have to accept that it's a possibility that it might happen to me. Fingers crossed it won't, but it is possible.

Regards

[Marlene]

Thanks for posting this in separate thread. It really highlights the complexity of bone marrow diseases. In your case, anemia was really a symptom of the low copper.

[cathybee1]

Ah Chirley, the Professor may be a smart man, but it seems like all he did was to give you bad news! I am glad that you have had such good response to the copper supplementation so far, in terms of resolving the MDS symptoms, and hope the neurological issues continue to improve as well.

The report from Dr. Paquette at UCLA arrived Friday. Neither of the two University hospital pathologists who looked at Bruce's bone marrow slides saw a clear cut case of MDS, however, Dr. Paquette thinks that's what is going on. A diagnosis by exclusion.

Dr. Paquette nixed the copper deficiency as being an important factor contributing to anemia. And the local hematologist talked to a doctor from the Mayo Clinic, who said Bruce didn't fit the profile for someone with copper deficiency anemia.

As the IV supplementation has not normalized Bruce's copper or ceruloplasmin levels, Bruce is leaning towards stopping the supplementation. He is going to continue transfusions, and do a trial of Exjade.

[Chirley]

Hi Catherine, I understand Bruces' decision to stop the copper supplementation.

I was also told that my BMB and blood results weren't consistent with copper deficiency but my blood tests did definitely get better with copper replacement. I suspected at the time that the Vidaza had started to work and that's why my blood results had improved and I put this to my hematologist. He just said that if it had been a Vidaza response I would have relapsed once the Vidaza was ceased. I still have doubts about whether it is the copper helping or the result of Vidaza but I have to go with the hematologist and defer to his knowledge.

The same article I saw about the man who went blind also mentioned that untreated copper deficiency can progress to leukemia and certainly my blast level was increasing.

I have to admit to considering refusing any more copper treatment and just having transfusions when needed. it's just a matter of quality of life versus length of life. I have started to hate my visits to daycare for copper. At least with transfusions it would only be one visit every two weeks or so and there is no evidence to show that copper replacement will stop neurological deterioration let alone improve the damage already done.

The daycare I go to for treatment are having Christmas week off and only having minimal patients the following week, so my treatment has been pushed back a couple of weeks anyway and to try and get my blood levels up again I'll have to have daily visits for a couple of weeks and , frankly, I'm soooo over them. I'm sure my doctor thinks I asked to have more time off and doesn't realize that they just want to have less staff on over the holiday period. Anyway, I'll think of it as my opportunity to have a nice long think about my treatment options.

Regards

[cathybee1]

Chirley, I do understand why you desperately need a break from the daycare. The hassle of your situation must be exhausting. Bruce is in a little bit better situation in terms of being able to get most of his copper treatments at home...the downside has been very high out of pocket expenses for supplies and IV supplements. The doctor wrote a letter for our insurance, but so far, none of the costs have been reimbursed.

Bruce also wants to see if his copper levels will drop much without the supplementation...since they haven't risen noticeably with the IV copper, will the reverse be true?

In his report, Dr. Paquette offered Revlimid and Vidaza as treatment possibilities. But since Bruce is already so neutropenic (and platelets are getting low as well), Bruce didn't want to deal with possible side effects from those drugs now.

Bruce's hematologist called today. He doesn't want to start Bruce on Exjade immediately because some of Bruce's liver numbers aren't so great. So, the liver biopsy is back on the front burner again, so the doctors can see how much damage from iron has actually occurred.

[Chirley]

Hi,

Well, I did it. I have cancelled my daycare appointments. It's been 4weeks since I've had IV Copper and the last time I was without parental copper I relapsed into bone marrow failure within 10 weeks. So the next 6weeks or so will be interesting to say the least.

I have noticed my neuropathic pain in my feet has worsened and I have increased spasticity and stiffness in my legs but I expected my neuro problems to get worse so maybe it's psychological.

Catherine, hope you and Bruce had a lovely Christmas and New Year. Mine was a little sad because my Dads only remaining brother passed away. My uncle died in Sweden and Dad felt so useless being on the other side of the world and not being able to be there for him when he was so sick. My Dad is acting like nothing happened but I can read him like a book and I know he's hurting. I brought out an old photo album and sat down with Dad and asked him questions about the photos and he was soon talking about his brothers and sisters and telling funny stories from his childhood. I hope it helped him to talk about it just a little.

I was wondering how Bruce is going without his copper treatments. Is he
requiring more transfusions now? is he going to start treatment with the Revlimid or Vidaza?

We are just about to get a storm so I had better go and bring my dogs in..they are both very well..I'm very blessed.

Regards

[cathybee1]

Sorry I haven't been on for a while...stuff has been happening here.

First, Chirley, I am so so sorry about your uncle. I'm glad you could be there for your dad. I hope that this time away from daycare will be restorative for you psychologically and that you can enjoy the summer with your pups. I so wish that there were some better choices for you.

Bruce decided to not try the suggested pharmaceuticals. The odds the specialist in L.A. gave for Revlimid or Vidaza working were pretty low, and the immunosuppression side effects of both drugs pretty daunting. So Bruce wants to continue with transfusions.

Bruce had his liver biopsy 5 days ago in a hospital (with conscious sedation thank goodness). The biopsy is being evaluated for both iron and copper. The hematologist called today to say that preliminary results of the iron testing indicate that Bruce has moderate fibrosis in the liver which the hematologist said were due to iron deposition. I wasn't here when Bruce got the call. Bruce told the hematologist he wants to go ahead with a trial of Exjade as soon as all the insurance paperwork allows.

The good news we got today is that Bruce had bloodwork in hospital before the liver biopsy at which time his hgb was at 9.1. Today, he had another blood draw, and his hgb was at 9.4. Different labs but it has been a month since the last transfusion, and it was a pleasant surprise that his hgb levels are still holding. The other pleasant surprise was that the MCV levels are still near normal.

Bruce has had no IV copper since before Christmas. The blood draw today was the first testing for copper done in a month, and we won't know where those levels are at for another week.

For now, Bruce continues to feel well, and yes, we are grateful for our blessings too.

Hugs to you

[Chirley]

Hi, I have just returned from a visit with the Prof of Metabolic Medicine.

I can't say I was looking forward to this visit because I found him quite rude and abrupt last time. Well, he was different today. Whew.

I was given the results of my chromosome studies from last visit and I've been found to have del 15q which oddly enough has no prior relationship to either MDS or copper deficiency. So now they are scratching their heads yet again. Apparently he thinks I also have some portions of the same chromosome that while still present, have been switched off.

Del 15q is associated with Prader Willi Syndrome but I have none of the physical or behavioral features (except insatiable hunger, but doesn't everyone). So now, I have ? MDS, copper deficiency bone marrow failure and myelopathy and Prader Willi.....seems like the more you go to doctors the
more they find.

As a result of these findings they are now adding copper testing to the investigations they do on children with suspected Prader Willi, so hopefully my situation might produce some good.

Ferritin remains at 1600 something. I told him that I had decided to discontinue copper replacement and he was predictably not very happy with my decision. He thought I would decline neurologically quite quickly and then he "will be left to pick up the pieces". I told him that as a female I reserved the right to change my mind if or when I couldn't tolerate the symptoms any more. He said it was part and parcel of Prader Willi to be non compliant and that's why I won't do everything they tell me to do. Sometimes instead of telling me to do something it would be nicer if they asked but hey, what would I know, I'm only the patient.


There is a doctor coming here from England in a few months time who specializes in Prader Willi in adults and he wants me to see him, so that could be interesting.

I have guessed the spelling of Prader Willi, that's how little I know about it so I suppose it's Google time again. Life is one long lesson isn't it?

Regards

[Birgitta-A]

Hi Chirley,
Yes, your disease is really getting more and more complicated . Hope it will be OK to discontinue copper replacement at least for some time!
Kind regards
Birgitta-A

[cathybee1]

Chirley:

Yes, all this does complicate things a little. And now if you don't want to do something a doctor thinks you should do and/or you're hungry, it's because you have a chromosome abnormality? Wow!

Bruce is waiting for the Exjade to arrive (supposedly it's coming in the mail). We still don't have the results of the copper test done a week ago, but that's not unusual. So, no news here, except it's VERY cold.

Hugs

[Chirley]

Hi Birgitta. Yes, it's quite baffling and I think it's creating some curiosity/excitement for the Prof. On my part I feel quite detached from it all now. It's as if it's happening to someone else and I'm a slightly bemused bystander.

Catherine, that's exactly what I said to the Prof....I can do and eat anything I like and blame it on my genes . I said it as a joke but I don't think he knows what that is so I didn't get even a smile, oh well, I tried to lighten the mood.

My parents are both in their eighties and the Prof has given blood test requests for them to both have chromosome analysis and copper levels. They have both agreed but I think they are puzzled by the whole thing.

Ahh, that medical journal article the neuro is writing about me is getting more interesting with each test I have. Maybe I will ask for royalties!

Is Bruces' Hb still holding? No transfusion lately?

It's very cool here considering it's summer. I still have a duvet on the bed at night, and it's raining day and night. Still it's nice to snuggle into bed on a cool rainy night isn't it?

Regards

[Lbrown]

I hope your poor baby professor doesn't strain himself picking up the pieces!



Honestly. Some people!

Deb

[Chirley]

I'm confused. Not hard to achieve but still....

My neurologist rang me this afternoon and told me that they don't know what the deletions on long arm 15 mean. This is different to what the Prof told me but I agree with my neurologist that I don't fit the Prader Willi profile so the deletion is likely to be more distal. So I Googled.....big mistake....

Del 15q interstitial deletions have been associated with poor prognosis MDS and post MDS AML.

So now what do I think? The Prof is going away for 3 months, the neuro is clueless about MDS and I REALLY didn't want to go back to the hematologist just yet because I was declining further treatment.

Denial and procrastination sounds good.

Regards

[Birgitta-A]

Hi Chirley,
You know as long as nobody knows if you have MDS or if your symptoms depend on lifelong copper deficit you shouldn't worry about what del 15q means to MDS patients.
Kind regards
Birgitta-A

[Lbrown]

I agree with Birgitta. And I also think just because they find some association between this and that doesn't mean one causes the other. You should be in charge of your treatment, which means it is your right to refuse treatment.

Deb

[cathybee1]

I'm also with Birgitta on the del 15q.

Bruce will probably go in for another blood test next week. It is weird, but I am getting able to tell from the sound of his voice whether it is transfusion time. He has had a few experiences like this over the course of his anemia. Plateaus and then ka-boom, the numbers drop big time. But so far, so good.

How are YOU feeling??

Hugs

[cathybee1]

How are you doing, Chirley? Inquiring minds want to know...

[Chirley]

Hi,

Thanks for asking. I'm still feeling okay.

I think I'm becoming anaemic because I'm pale again (I actually like being a little pale....makes me look younger). I'm also a little breathless at times and I have a mild chronic headache which are all my indicators that I'm due for a blood transfusion.

If I'm right and I do need a transfusion, it will have been a disappointingly fast decline. Its been just over 7 weeks since I had my last copper treatment and almost 9 weeks since my last blood test. The last test showed Hb well and truly in normal range and copper just below normal range. My blood levels aren't affected until the copper is pretty much near zero.

Neurologically I am having a very slow but steady deterioration. Walking is such hard work and dangerous because I'm so unsteady that I could easily fall that I spend most of my day sitting and reading or being on the net. I keep putting off getting a wheelchair because there is some kind of psychological barrier that I'm avoiding even to try and understand. My GP says it's denial, I say it's optimism. I'll deal with it when I have to.

I have an appointment on Thursday to have my port flushed and also to see the hematologist. I want to discuss the chromosomal abnormality with him. I've been thinking about it and realized it must be new damage because I certainly wasn't born with the syndrome caused by this particular deletion and because it was not found on the 10 or so BMBs I've had done.

I rang Celgene and spoke to a patient liaison person who said there have been no reports of this deletion being caused by Vidaza but that they were going to document it as an adverse event. I gave them permission to contact my doctor about it but only after I see him on Thursday because he has not been told of this finding yet.

My little dogs went for their yearly vaccinations and check up this morning and both were given a clean bill of health. The vet said that my old (13) white dog is doing incredibly well considering she has had Addisons Disease for 9 years and had an obstructing liver tumor that almost made her bleed out about 4 years ago. The liver tumor disappeared without treatment and the vet said he had never seen that before and he considered it a miracle. The arthritis medicine is working very well for her and she's a playful old girl again.

I'm very lucky.

Going to cook my dogs sausage and mashed potato for dinner as a treat after the needles.

Regards

[cathybee1]

Thanks, Chirley, for the update. I am very glad to hear from you and to hear you have an appt with your hematologist. I am very sorry about the neurological issues.

I am so so happy about your pups check up!!

I heard you are having a very hot summer.

Bruce is feeling much better since the last transfusion. His copper results finally came back from early January. It was at 61 (-10 from normal) -- it has been lower, so for now he is taking an oral copper sulfate supplement and calling it good. And he is still tolerating the Exjade.

Hugs to you,

[Chirley]

Hi,

I've just returned from my haem appt. So much for being tired and headachy....my blood test was very nearly normal. Hb 132!! WCC 4 neuts 2.2 and platelets 157. The only abnormality was my usual low lymphocytes.

I also had a copper level taken but I won't get results until next Tuesday.

I am over the moon that I have not had copper replacement in 8 weeks and my CBC is so good. My doctor is extremely surprised, to say the least, but doctors being what they are is a little more reserved. He said that if the chromosome deletion is new it is an indicator of MDS after all. He even mentioned the dreaded transplant word. Previous BMBs wouldn't have shown this deletion because it was a micro assay and these aren't done on BMBs normally so there is nothing to compare it against. We just have to wait and
see if my parents tests show the same abnormality we won't get those results for at least three months when the Prof is back in the country.

I'm assuming if it is MDS after all, then the 5 cycles of Vidaza that I had were incredibly effective despite my blast count increasing when I was having it.

It also turns out that he didn't notice that I'd stopped having treatment and the daycare centre didn't tell him that I'd cancelled so he was a bit perturbed about that but I told him that my actions were vindicated by the blood results.
He had to agree . He has asked me to see him again the next time I have my port flushed in 2 months but if I have any problems in the meantime or even if I just change my mind about the copper treatment he wants me to ring him. He also told me that he supports patients in their treatment decisions and he will continue to be there for me no matter what I decide to
do.

Next visit is to the neurologist who won't be quite so accommodating. Oh well, can't have it all.

Regards

[cathybee1]

Lots of good news here. I would be so over the moon too -- yay! I hope your CBC levels continue to hold, perhaps that might indicate a longer lasting effect of copper supplementation?

I'll keep my fingers crossed your visit to the neurologist goes better than expected too.

Hugs.

[Lbrown]

Awesome CBC! Do you feel a little less tired now?

I find sometimes I feel like my counts have to be in the toilet judging from how tired I am, and then I find out they're not so low after all. It usually perks me up. I guess it shows some of it is the mental strain.

Hope the results stay that great and your doctor is right about it being your decision as to what treatment to do.

Deb

[Chirley]

Hi, I almost can't believe my results. I'm definitely pale and I am headachey, tired ++ and just the last day or two starting to get breathless so when I found out yesterday that my CBC was good, I thought how much of the physical symptoms can be influenced by the mind.

However, today i still feel the same although I know I shouldn't. I hope it's just temporary because we are finally having some typical summer weather. Hot, humid, daily rain showers etc basically ugh. I was warned by the neurologist not to get hot (just like people with MS) so maybe that's got something to do with the way I'm feeling. I have an air conditioned house but sometimes you have to go out. At least, that's what my dogs tell me .

It's my Dads birthday today, so Mum and I are going out for lunch. Dad asked me to do this for him as a present because Mum has been in a bad mood for a couple of weeks and he wants a break, he thinks it might also cheer her up. I love my Mum very much but I have to admit she's a highly volatile, bad tempered, opinionated little person. She's 80 and Dad still finds that cute and amusing, life with her is not boring! They have been married nearly 63 years. I arranged for them to get a letter from The Queen for their 60th anniversary and surprisingly, they got one from the (then) Prime Minister and his wife as well.

Regards