Newbie and simply confused!

Hi.

My name is Gracia from Malaysia.  I'm a Chinese diagnosed with Alpha Thal 5 years ago.  My hematologist suggested I also have other hemoglobinopathy when she first saw me.

During my teen I'm always lethargic everytime I run, even finishing 100m, I would feel as if my heart would burst with all those blood pumping.  I always dismissed it as having no stamina as I'm not a sporty person. 

In my 20s, I started working and stumble on a chance to undergo a blood test by a specific pathology lab which was paid by the company.  Only then I found out I'm anaemic and further run the HB Electrophoresis which suggests I have normal HBA and HBA2 fractions, with negative HBH inclusions.  There, I thought I am normal, just a little bit anaemic (10.1g).

When I was having my first baby in 2005, things started to change.  The first few months are fine(10g) till 2nd trimester kicks in.  I started having low blood count (HB  7.4-8) and the antenatal clinic nurses started prescribing me iron tablets and sent me to see the GP at the local polyclinic(govt).  The doctors asked me to run HB Electrophoresis but the test did not came back until this day.  The GP increased the iron tablet from 2 to 4 and 6 and the last straw saw me instructed to take inferon jab for 10 days but the HB level never went up. 

During my pregnancy I also take the initiative to see a gynae as I was a bit concerned as it was my  first pregnancy.  I told my gynae what was treatment I was undergoing at the government polyclinic and she was totally shocked that the doctor injected inferon without checking on other test.  She quickly ran more lab test and which shows the following result:

Haemoglobin A2    2.3%
Haemoglobin F   3.2%
HbH inclusion bodies    Not detected
Ferritin   432 ug/L

As a result of this she suggested me for transfusion which was done at the government hospital and I was given 2 pints and delivers by induction 2 weeks later.  I delivered a healthy baby boy who is now 6 years old.  He has Alpha Thal too. 

After the delivery, I managed to get myself referred to the haematology specialist clinic(the only one in the state with only 1 specialist and multiple doctors who come and go as some may be doing their housemen as the specialist will only see the severe and need her attention case).  Only then I found out that I am Alpha Thal after she sent for DNA test.  The haematologist suggested I may have 1 gene deletion therefore its alpha trait.  At this point my ferritin level is 1246.

On my 2nd pregnancy(2006), the pregnancy starts with low HB but I was prepared with the assistance from the specialist clinics from both haematology and the gynae. However, things run haywire with my heart rate starts palpitating to 120 p.m. which saw me admitted to the hospital twice with HB.7.4 which the doctor from my haematology clinic says I’m fine on the first admission; I can cope with HB 7.  Only on the 2nd admission the doctor decides to transfuse as the palpitation do not seems to subside.  After the transfusion, it seems to solve the palpitation problem and I managed deliver by baby girl safely by term.  My girl is also tested and she has Alpha thal too.

At this point I am totally confused whether I am a thalassemia trait or HbH because today I went to the haematology clinic bi-annual check-up and my hb is 9.3 and the doctor was writing on his case note I have HbH?  I totally forgotten to ask him this question as I was too engrossed trying to remember what I wanted to ask him. 

Can someone from Apha thal trait moved to become HbH?  As far as the years gone by my hb was on the 7-10gm average.  It gets worse with age, I presume so I am rather concerned having transfusion in the later of my life.  Throughout my life, I had never passed out even my Hb was low. 

In 2005 my haematologist run, α – DNA studies with the following result:
-No α SEA deletion detected
- other α mutation not available
MCV – 77.5, MCH – 26.2  Few ‘H’ inclusion seen
HPL C – HBA2 < 3.5
HbF – 2.8%

Neither I know how to interpret this result as I copied this result(for own reference) as it was sent to Institute of Medical Research for 2nd DNA test which I presume the HBH?

I have mild splenomegaly(14.8cm). Frequently I can feel my heart beating while occasionally feels that is beating far too slow (50-60 p.m.) which the doctor says today its normal as the thyroid test is normal??  I had a bad upper back pain for years and never actually bothered about the pain which I dismissed as too much sitting on the desk until I stopped working over a year ago and the doctor says normal too?  Another doctor who sees me only had 5 minutes seeing me and decides that I’m having a gout(frozen shoulder) at 369 umol/L which is within normal range when I complained my upper back pain.

I frequently feel dizzy especially if I had a low HB at times if its too low(around 8+) I used to pass by my office days doing nothing productive as I told my colleagues, I can’t “think”.  Luckily my colleagues understand yet I would plough through the days trying to be “normal” although I had to lead the marketing office with busy marketing schedule.

I saw HBH writing on the forum and I agree with what he is feeling as I felt the same too.  Being categorised as “not too sick”, sometimes I was half wishing the doctor would be more caring when I see them than telling me oh... that’s normal.  Then what is abnormal then?  I told them I had palpitation, they sent me to echo test, and that’s normal result.  Then the thyroid function test, normal result again.  Uric acid, normal range. 

Bilirubin 50 umol/ L (<21) which gives the yellow urine which seems to be darker than tea at times is said to be normal. 

ESR 14 mm/h (<21) is still normal.

Then, what is all this pain coming from?  I half thinking I must have arthritis then, but all results doesn’t tell anything at all.  I am indeed worried, what is the future lies for people like us.  How does one cope with a life undergoing uncertainties as we age.  I am worried with the future whether with the excess bilirubin whether I’m going to get liver and kidney problems, excess ferritin for heart problems, hypertension and diabetes as it’s in my family’s root.

At this point of time Alpha trait --> Alpha HBH, well I’m just simply confused!

Hi Gracie,

First, do NOT EVER take iron again in your life. Your doctors have done you a great disservice by prescribing iron and your ferritin level is far higher than normal. This may even be contributing the the pain problems you have mentioned. Iron is basically a poison when there is too much in the body, as your body has no natural method of removing excess iron. Low hemoglobin levels can lead to the body absorbing more iron than is needed, so thals have to be very careful about adding to that iron load in the body.

I am a bit confused as to how the diagnosis of alpha minor was made. Your reports say there is no sea deletion and no other alpha mutation available. Your HbF is higher than the <1% expected with alpha minor. Your MCV and MCH are also slightly higher than what would be expected. Your results actually look more like beta minor. Was hemoglobin Barts detected in your babies when they were first born, or did another DNA analysis find an alpha deletion in you? I need to be certain before further commenting, as the HbF level makes little sense in the context of alpha thalassemia.

Hi Andy,

Thanks for your advice.  I basically had not taken any iron supplements by reading the labels but food wise, its rather hard to ignore the food chain  as I need to cook for the family.

The DNA analysis is performed by Institute of Medical Research whilst the Haemoglobin HPLC studies are performed by a local lab.  I do not know the significance of this with the DNA analysis but my haematologist has looked at both result and confirmed I am alpha thal, except I don’t know which type(which I am confused). I am thinking of asking my parents to do the test just to confirm so that they would know what to eat and what not to eat as my dad has asthma now and my mum has diabetic and hypertension.  My mum’s parents died with heart attack and another with cancer so I was a bit concerned about their health too and mine too as I feel getting older is really getting a toll of my cheery mood at times.

I would agree with the haematologist as I have 3 cousins who are alpha thal too from my mum’s side.  One of them are more severe, I was thinking he was having HbH as he was as pale as me and both his parents are alpha thal.  The last time I saw him this month, he looks a bit fat, but I can’t shrug it off as his spleen are probably enlarged a lot as I saw a lot of the beta thals whenever I went to the thal clinic.  I didn’t ask him as it was down rude to ask!  Having thal is a hush hush here as parents tend to protect their young by disclosing this information.  I only knew that my cousins are thal from my mum when I was hunting for answers for my anaemia(after going for rounds and rounds of merry go round) to finally get to the conclusion.

The haematologist actually performed 2 DNA analysis, one in 2006 and another in 2008(I  think) cos she said she was curious and there are much better technologies in 2008 to do the testing.  She has a lot of beta thals and not many alpha thals, I suppose judging from the clinic I went to are all waiting to been transfused. 

What kind of result do you want to see, I need to dig my file(which i own) and half that I don’t own belongs to the thal clinic so I can’t provide the more details that you need.  The problem with doctors here are they tend to change everytime I go to the clinic so no one are actually looking into my problem.  The “best” answer I had yesterday was totally put me off with... everything being “normal” so I really wanted to question, the doctors when is the right time I feel “not normal” I should be seeing them.  Do they want me to actually passed out before they find out “more information”.  Even these days, I carry my phenotype with my purse, just in case....

Thanks and appreciate your thoughts.

I would like any results you've been given for the DNA analysis and also do you know if the beta globin gene was also checked in the DNA analysis? Your HbF level does not seem possible if only alpha is involved. I am wondering if you might carry a deletion of both alpha and beta genes. That would help to explain the HbF level and would also be of some help in suggesting advice.

I do want to answer one of your questions now. Your MCV and MCH are much too high for HbH disease. MCV is expected in the low 60's and MCH below 20 in HbH.

Hi Andy,

I think I made 1 typo error with the DNA anaysis performed in 2006. 

It should read :
No SEA deletion detected
Other alpha mutation not available then

Missed out the then... sorry, that's why my story doesn't make sense and you can't make any comment.

I managed to dig out some photocopy of DNA request screening for my son as they state the result of the screening from my daughter.  My daughter has Codon 59 deletion.  I am not sure about my son, I supposed he should be the same too?  since they both inherited my bad gene.  Euu.... I was still thinking about another baby... hm... should I, should I not?

I don't know the whether my husband is a thal carrier as his Hb Electrophorosis is not done and he refuse to do it as he said he's healthy(Man's ego).  He has successfully donated blood everytime for the past 10 years leaving me feeling more "down".  How I wished I was in his position there...
Hb 17.1  MCV 85.1   MCH 28.2
My hematologist said he probably is normal based on these readings.

I know the above may not be related but does Codon 59 deletion mean anything to you?

That is very helpful. I will comment more this weekend after researching that particular deletion, which is considered an unstable deletion.

Dear Andy,

Thanks for the info.  I don't know why the doc put HbH diagnosis.. that's been helpful, afterall, the doctor who wrote it down is far too young to be a doctor ..hehe  All this while I saw the previous docs see me as trait/intermedia + hematologist won't confirm to me what type... with a probably 1 gene deletion + other hemoglobipathy?

Would appreciate your help a lot, it was good to rule out HbH...

Thanks!

Codon 59 refers to a gene mutation that creates an unstable hemoglobin. The hemoglobin causes both ineffective erythropoiesis (bad red blood cells) (thalassemias) and peripheral hemolysis (breakdown of red blood cells) when found with another alpha mutation or deletion. An unidentified alpha mutation was also apparently detected in you. Even though two genes involved in alpha usually means few if any symptoms, this is not the case when codon 59 is involved. It can manifest similar to HbH as it has with you, even though technically, it wouldn't be considered as HbH. Testing will also show only a small quantity of hemoglobin H. Alpha thalassemia is normally milder when the gene is deleted, but when there is a mutation rather than a deletion, a more serious thalassemia will manifest, as it has with you. This is why your doctor referred to it as HbH, because the severity is worse than most two gene alpha thalassemias. 

As I said earlier, iron must be avoided. Do not take iron in any supplement. Your body will already absorb more iron than you need because of the low Hb level. This is a common problem with HbH and iron is always prohibited. Take folic acid daily. I would suggest 5 mg daily. I would also suggest a B complex and magnesium supplements, to help the red blood cells develop and last longer. Drink tea with your meals, as it can help inhibit absorption of more iron. I would also suggest having your ferritin retested. If it is not dropping, there are a couple natural methods to try before using more extreme measures like chelating drugs. There are certain foods to avoid and a list of drugs and chemicals that must be avoided as they can cause a sudden hemolysis, where red blood cells are destroyed and the Hb suffers a sudden drop. This list can be seen at http://www.thalassemiapatientsandfriends.com/index.php/topic,3410.msg34830.html#msg34830

If your Hb suddenly drops at any time, review your diet to see if any beans or legumes may be involved or if you might have had exposure to any chemical fumes. Even breathing in gasoline fumes at a gas station should be avoided. Meats cooked over charcoal can give off benzene fumes, so avoid exposure to that smoke also.

Dear Andy,

Thanks for your lengty explaination.  So I'm alpha trait with codon 59 deletion afterall?

I hope my Children will not suffer the same consequences that I suffer.  They do seem to have normal HB (12-13) and are rather active children.  I hope I can maintain my HB without too much drop as it seems these days are more tougher to get through as I age carrying excess iron for years.  I will do the ferritin test again.  I'll check with the local polyclinic whether they will do it, if not I will have to get the local labs to do it(through doc's referral, at least I keep a copy). Its cheaper to do the test in the government clinics as its subsidised, as currently I'm not working. 

As for supplements, will multi vitamins do?  I recently bought one, natural factors multivitamin & mineral complex (iron free) which is manufactured from Canada.  Are you familiar with it?  Its very hard to find multivatamins here(iron free).  I don't like supplements, it feel like taking drugs everyday, so i don't need to take so many different tablets with multivitamin.

Is there any specific teas that I should drink?  I normally drink Chinese tea, Japanese tea or black tea although I don't drink it so frequently.  I like coffee more. 

Any tea will do. The purpose is to inhibit iron absorption from your food. This is especially important in meals that contain high iron non-meat foods like dark green veggies. Minimizing red meat will also help as it is the highest in iron. A multivitamin is good, but it will not get you enough folic acid. This should be taken daily when alpha thal is present. These are nutrients and not drugs and there is a definite increased demand for certain nutrients when red blood cells do not last a normal lifespan. The red blood cell turnover is faster, creating a need for the B vitamins, folic acid and magnesium needed to build red blood cells. The breakdown of these RBC's also leads to oxidative stress. A diet high in antioxidant foods is recommended. I must also stress that vitamin E is a good antioxidant that is normally found to be deficient in thals. I have take vitamin E daily for over 35 years and absolutely swear by it.

Codon 59 mutations of the alpha gene can more or less place a patient in the next category. There are recorded cases where true HbH that included the codon 59 mutation resulted in fetal hydrops, which result in death of the fetus. This normally only happens when all 4 alpha genes are affected. Your test results implied that another unspecified alpha mutation or deletion is present, along with codon 59. This would explain your experiences. Because the unstable hemoglobin breaks down more quickly, you will see the effect in the spleen. Unlike what is normally happening in thalassemia, this cannot really be blamed on the spleen, as it is the nature of the hemoglobin itself that causes the breakdown of red blood cells.

There is little known that will help alpha thal. Folic acid is the one thing universally recommended. Your case is interesting because there is the presence of HbF which is not normally observed with alpha thal because there are not excess alpha chains to combine with gamma globin to form fetal hemoglobin. I did see mention in a case of siblings with a similar alpha make-up as yours, who had another gene factor that resulted in measurable HbF levels. Even though your HbF is only around 3%, this is significant and actually raises your total Hb slightly.

Please review the link from the previous post about foods, drugs and chemicals to avoid. This can help you avoid sudden hemolytic crises. Physical stresses in general can add to hemolysis, as you've seen during pregnancy. Pay particular attention to beans and legumes. Fava beans must be avoided completely, but some people report problems with other various legumes. If you see no sudden change in how you feel after eating beans, you are most likely OK, but do avoid fava beans completely.

DNA testing for alpha thal has advanced much in recent years, but there are specific guidelines to follow and it takes an experienced tech to give a complete and accurate diagnosis. Your results indicate a codon 59 mutation is present. The results also indicate another unspecified alpha mutation or deletion is present, but the testing was not sophisticated enough to identify it. I would say the only thing you really need to know is if these two defects in the alpha genes were noted in a single pair of alpha genes or whether they were on the two separate pairs. If the latter is true, your children could only inherit one half of what you have. This may be the case if their Hb stays normal and they show no problems such as an enlarged spleen.

If upon further ferritin testing, chelation or bloodletting is suggested, please let us know. In cases of high ferritin that is not dangerously high, as is sometimes found in non-transfusing thals, I suggest using natural chelators first before resorting to chelating drugs.

Dear Andy,

Thanks for the inforation.  I will go through the forum and get more details.  I don't think I ate any fava beans, its  probably not a popular bean here.  Never heard of it before. 

I will test the ferritin level again, I guess it may still be overload but may not as high as 1000 if I do my calculation right cos I haven't had any transfusion for 4 years.  My hematologist said its not "high", acceptable  but it bring years to bring it down.  Goodness know what its doing to my body to have it for years!

I think my case is different, that's why its very hard to find information over the net, needless to say, to understand it.  I only hope my children may be different, and not suffer from what I have now.

Will keep you posted once I had my ferritin level checked.

Thanks!

Hi Andy,

After searching google... now I know what's fava bean... no wonder I've never heard of it.  It's more locally called broad bean here usually made roasted for consumption.  Don't worry, I don't crave for these stuff.  My mum used to tell me these beans caused jaundice in babies if you take it during pregnancy don't know whether that's myth or truth.  Now I know... hehe..

Thanks for the info.

Hi nebiee,Try and drink a tea at least 2 a day when I drink tea i feel much more ok,then when im not.I try it on myself for few days and I come back to drinking my normal black tea with a bit of milk every breakfast morning i wake up early around 6 am,and then i take tea afternoon.

Thanks monima2 for the advice.

I was trying to do that now.  Been really lousy these days.  Slept for 8 hours, kept waking up yet, still felt as if I haven't slept at all. 

I have not read the posts from others, but your pain can from high iron. For the rest I am uneducated.

Dori
Netherlands
another hemolytic anemia pyruvate kinase deficiency