NEW TO FORUM - AND CLARIFICATION REQUIRED RE DNA REPORT

Hello,

I am new to this forum and have learnt so much by reading your posts.  I have been interested in thalassemia for many years as my brother was diagnosed with the b-thalassemia trait when he was young. Even though I was not given a thal carrier diagnosis, my HB, MCV and MCH have always been on the low end and the doctors have left me in the dark for many years.

My usual FBC shows:
HB: 118
MCV: 75
MCH: 25.
My iron studies are usually normal however my S TRF. SAT is often high (about 56). Not sure what this means and doctors I have seen over the years have never understood either.

My HB electrophoresis is: HB A2 (3.3%) and my HB (F) <1.0%.
I finally convinced my doctor to give me a DNA test for thal and it came back with:
PCR: NO DELETIONS DETECTED.
Heterozygous for a mutation in the a2 globin gene.
Poly A, AATAAA>AATAAG.
The doctor was not able to explain what type of trait this is and I was hoping someone could clarify for me that would be great.  Thanks in advance.

PS. I am of Greek background.

Hi SaltySea,

Poly A, AATAAA>AATAAG is an alpha thalassemia mutation, that reduces the production of alpha globin. In a carrier like yourself, it can result in a slightly low Hb level. The MCV is low, as it always is in thalassemia, because some of the red blood cells are smaller, reducing the overall average size. A clue that this is alpha and not beta would be seen with the combination of the low MCV and low HbA2 (HbA2 is high in beta thal minor), along with the knowledge that iron levels are normal. The result in a carrier can be from mild anemia to normal. When two of this gene are carried, it can cause a mild HbH disease.

Thanks Andy,

I appreciate your help and clarification. Can you please clarify your comment "When two of this gene are carried, it can cause a mild HbH disease". My understanding is that I do not have HbH but I can pass it on.

My ten year old daughter recently had a blood test and she has similar FBC data to mine:
Hb: 114 L
MCV: 72
MCH: 23

Normal iron studies.
Hb A2= 2.6
Hb F = <1.0

s FOL: >45
s TOTAL B12 569

I just got these results today.  Do I need to do DNA STUDIES to confirm her thal diagnosis and is so would it be the same as mine or can she have a mutation in the process. My husband does not appear to be a carrier of thal even though he is of Mediterranean background.

Thank you for all your help.  I appreciate it.

You carry only one alpha mutation. I suspect your daughter is the same, looking at her Hb, MCV and MCH.

The reason I made the point about HbH when two of these genes is carried, is that normally, HbH requires 3 alpha genes being affected. Your children will need to be aware of this status, so they can make informed decisions when they are adults about who they should not have children with. Potential partners should be tested to make sure they do not carry alpha thal.

Folate and B12 may both help keep the Hb up. With thal minors, it's best to keep the levels up at the high end of normal.

Andy, I appreciate very much that you have taken the time to get back to me about my thalassemia minor status and that of my daughter's.  We have ascertained that the thal gene has been passed on by my father's side of the family who live in Greece, but because we are the only ones in Australia from his family it has taken us quite awhile to sort out this puzzle. I personally find it amazing how this gene has traversed so many generations and continents; that is why awareness of its impact is so important.  Thanks again.

Thalassemia originated in the Mediterranean region and was passed around the world by explorers, armies, merchants and various types of travelers. There is quite a bit of it in Australia because many Greeks and Italians have moved there over the years. And yes, awareness is everything. Children always need to understand their carrier status as they get older.

Hi Andy,

It took me awhile to get a DNA test organised and completed for my daughter, who is now nearly 12.  You see, none of the doctors I had originally seen, saw the value in getting her DNA tested, even though her blood tests were indicative of thalassaemia minor and I am an alpha carrier myself. They kept telling me that minors are asymptomatic so my daughter should wait till she plans on having a family!!!!  

However I persisted to get the DNA test done (even though one doctor said getting a DNA test "is too academic" and another was not willing to get the lab to do it because of her age; due to the clinic's cost-cutting measures). On one occasion a doctor sent us off to a laboratory that did not do the test - a waste of a blood test and anxiety for my then 11 year old.

So I had to be very proactive and do the calling and research myself; called the laboratories in my town to find out which one did the test and whether they did it for children.  Most of the laboratory people were great actually and gave me lots of useful information and it was from them that I worked out how to ASK MY DOCTOR FOR A REFERRAL.

So it was just a matter of finding a doctor to give me a referral to do the test. It took lots of patience and diplomacy, but I went back to the doctor who said it was "all too academic", with step by step instructions on what needed to be done to get a DNA test organised and he finally agreed. Phew!

Today I finally got the report of her DNA result.  My daughter is heterozygous for the Poly A (A>G) mutation in the ALPHA2-GLOBIN, just like me.   This is great, we have a result, we have information.

I am sharing this part of my story as I did not find out until my early 40s that I was thalassaemic and this affected my well-being greatly; physically and emotionally.  I personally feel that information is not always "too academic"; but that it has so many practical implications.  As minors are symptomatic  having this knowledge can help us look better after ourselves and pace our lifestyles.  My daughter now has this knowledge and no longer has to go through her life not knowing why her blood cells are microcytic and hypochromic, and why her Hb levels are lower; and why she gets tired when doing too much high impact sport at school.

If any of the readers on this website have problems getting a test done, persist and ring around if you need to.   With advances in DNA testing, this should be more practicable these days.  What is lacking is not so much the technology, but the awareness of the condition.  

Hi SaltySea,

In my case, I did a regular blood test and then later I insisted on a hemoglobin electrophoresis and the results looked pretty clear. Is there any additional benefit one can get from a DNA test?

Hello

The hemoglobin electrophoresis that I did came back normal, even though my Hb and MCV were not within range. For years I was told I was not a thalassemic carrier but none of the doctors could explain the anomalies in my blood tests results.

I think having a normal electrophoresis is normal for alpha thal (not beta though). So it could not confirm that I had thalassemia without the DNA test in my case.  That is my understanding.
Are you alpha or beta?

Thank for you answer, SaltySea. I'm a beta minor according to the current results, but I did not do a DNA test, only a hemoglobin electrophoresis.

Ok. that might explain it. b thal minors can be picked up on electrophoresis combined with the analysis of the other blood tests. Not so with alpha minors. If anyone knows otherwise I would be happy to hear from them as this has only been my experience.

SaltySea, that is correct. Alpha thal carriers are difficult to diagnose unless a DNA analysis is done, as it won't show in electrophoresis, but it will show low MCV and MCH, which should lead to DNA testing once electrophoresis confirms nothing.