19W Pregnancy: Heterozyous Hb E, Alpha Thalassaemia (Wife), Beta Th minor Husban

Hi all, I am new to this forum and glad to know it. However, i am currently overwhelming worried because my GP has gave helpless intention that waste a lot of my time around in confusion since i was in 12 Weeks pregnancy. i am now 27 years olds and live in Australia

In my case, i have diagnosed with heterozygous Haemoglobin E trait, my husband is beta thalassaemia minor. We are waiting for the result of DNA mutation.  However, in my blood test report, there is the note that the alpha thalassaemia cannot be excluded. My question is:
 1/ is alpha thalassaemia and haemoglobin E trait the same?
 2/ I am going to do the CVS as my GP's suggestion, can the Hb E/ beta thalassaemia major children can have the normal life and grow healthily?
 3/ If Dr. suggest the abortion at 23Ws of pregnancy, any negative affects to the wife especially the future natural pregnancy?

Please help me.
Thank you so much in advance       

Helen,

1) No, there are two different genes that cause globins to be produced which then combine to form hemoglobin. The alpha gene produces only alpha globin. The beta gene produces beta globin. Beta thal, HbE and sickle cell are all disorders of the beta gene. When an alpha deletion (not mutation) is present, it can actually act as a moderator of the beta gene disorders, as a reduced amount of alpha globin is produced, which matches more closely to the good beta globin being produced.
2) Isn't it too late for CVS? I would think amniocentesis would be done at this point. HbE beta thal has a varying outcome, related to the type of beta mutation present. HbE beta zero can expect a worse condition (transfusion dependent) than HbE beta+.
3) It's pretty late in the pregnancy for abortion. I don't know if it will be considered or if it should be this late in the pregnancy.

If the fetus carries both, you need to know how severe the beta is. Is it beta zero or beta +? You should also keep in mind that patients born today have fairly normal lives and that will only improve as new treatments enter the market. There is a drug, Luspatercept that is in phase 3 trials and looks very promising for raising Hb levels in thals. Please don't look at the major form of thal as a death sentence. It is not. Well maintained thals today have pretty much the same health as non-thals.

Hi Andy,

Firstly, thank you so much for your detailed explanation. Finally, I have received the DNA result. Moreover, i did the CVS test last week and now still waiting for the result. To be honest, i am very scared and worried. However, can you help me with the DNA result? In my case, based on the our DNA test's result, can my baby carry the worse situation of Hb E beta zero?
My result: Heterozygous HbE, Cd26 G>A mutation in the beta-globin gene.
My husband's result:Heterozygous for the nt -28 A>G, HBB:c. -78A>G mutation in the beta-globin gene. A carrier of beta thalassaemia.

Thank you so much

This is a beta+ mutation.

My husband's result:Heterozygous for the nt -28 A>G, HBB:c. -78A>G mutation in the beta-globin gene.

Hi Andy,

i am now extremely confused and worried. The result of our fetus has inherited both parents' mutation. We have lived like in a hell during the past few days and to be honest, i do not know what is the reasonable thing that i should do in this situation? We really love our daughter but more than that, i do not want my babe have to suffer pains and future unexpected difficulties in life.
We have a session with the haematologist in the next few day to consult about my baby's health conditions. However, i am seeking to hear more professional opinions as well as experience from you and anyone to clarify me.
My questions are:
1/ How is my baby health conditions (problems) under this HB e/beta+ thalasseamia?
2/ What will the future problems that we (parents) should prepare to face if we keep the baby?
3/ I read about the feature outlook of people who carries the same type of thalasseamia, With no offence at all, will it happen to my baby?
4/ Are there any treatment to this disease in the world? How can i register for my baby? WE can take her to go oversea to do the treatment

I am looking forward to receiving your response
Thank you

I'll try to answer your questions, but HbE beta+ thal can have an unpredictable outcome.

1) Because the beta is + it does create the possibility of a less severe outcome. Many with HbE beta+ transfuse irregularly at most. Some have regular transfusions. This can be related to any other moderating factors present, such as carrying alpha thal or the XmnI polymorphism. In both cases, when present, the outcome will be more mild. Most parents with a child with HbE beta+ that I have encountered find transfusions are not needed early in life.
2) I would recommend keeping the baby. The outcome is not predictable, but the chances are it will be a less severe outcome. In addition, gene therapy is already proven to cure HbE beta°, the more severe of the HbE beta thal possibilities. In addition, phase 3 trials for Luspatercept are currently taking place. Earlier trials have shown that this drug raises the Hb and lowers the need for transfusions. In milder cases, like HbE beta+, it is likely to completely free patients from transfusion. The future looks very good.
3) If a baby needs transfusions, it should have them. Babies that are under-transfused will have physical features caused by bone marrow expansion, as the bone marrow tries to produce more red blood cells. Transfusion suppresses this and well transfused children do not appear different than non-thals.
4) Bone marrow transplant is the only currently approved cure but it requires a matching donor. Gene therapy is in trials and proceeding very well for this particular type of thal. I expect it will be approved in the coming years. Various drugs like Luspatercept are also in development. These drugs will make thalassemia much easier to manage.

In the end, much depends on the treatment available where you live. I would suggest finding out where thalassemia is treated in your area and contact the hospital and doctors involved and ask them what the future will look like for thal babies born there. If possible, have the fetus tested for alpha thal (which would be a good thing) or the XmnI polymorphism. Either of these would moderate the condition, making it much milder.