Pregnant and Seeking Advice

I should provide some background on my current situation and explain why I am seeking advice on your site. I have Beta Thal intermedia and my husband has hemoglobin E tract. We have been trying to conceive for 7 years now and finally got pregnant naturally. I am currently 17 weeks and found out through CVS results that my baby has normal chromosome results but unfortunately baby inherited both my Beta Thal and my husband's hemoglobin E (25% chance explained to us from several geneticists). We are uncertain of what to do and what we can expect on the severity of the condition that baby will face. Do you know what the chances are % that baby will be Beta Thal major vs. like me intermedia or minor?

Thank you in advance for your help!

Hi and welcome,

The severity of HbE beta thal is usually determined by the severity of the particular beta mutation, but even then it is not totally predictable. If you have the DNA results for the beta gene (the exact mutation) I may be able to give more information.

I am assuming you are referring to the baby's DNA results. Is this correct? I'm not sure of my exact mutation but I am carrier and do not require transfusion.

Sorry. The beta globin gene mutation is called -28A>G (typically associated with beta thalassemia intermedia). Thank you again for your help!

Thank you. I will try to research this later today.

The -28 (A->G) beta+ mutation is listed in the PSU data base with no comments about the phenotype or clinical presentation. It does mention that it is found combined with HbE.
 http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=769

I have not found much mention of the -28 (A->G) beta+ mutation online. The one study I found that includes this mutation combined with HbE found that in those in that study who had HbE -28 (A->G) beta+ mutation were all intermedia, with no majors.
http://www.ncbi.nlm.nih.gov/sites/entrez/18951049?dopt=Abstract&holding=f1000,f1000m,isrctn

Blood Cells Mol Dis. 2009 Jan-Feb;42(1):32-5. Epub 2008 Oct 23.
Molecular, hematological and clinical aspects of thalassemia major and thalassemia intermedia associated with Hb E-beta-thalassemia in Northeast Thailand.
Nuntakarn L, Fucharoen S, Fucharoen G, Sanchaisuriya K, Jetsrisuparb A, Wiangnon S.
Source
Graduate School, Khon Kaen University, Khon Kaen 40002, Thailand.

Abstract
Hb E-beta-thalassemia is the most common form of beta-thalassemia found in Thailand. The disease exhibits a varied clinical expression ranging from severe transfusion dependence to relatively mild thalassemia intermedia. We evaluated the effects of primary and secondary genetic factors in modulating the hematological and clinical presentation of 148 northeast Thai patients including 103 severe thalassemia major (TM) and 45 thalassemia intermedia (TI). Among 148 cases examined, eleven different mutations including two novel ones; (beta(33/34 (-G)) and beta(IVS2#815 C-T)) were identified in trans to the beta(E) gene in two TM cases. The other 9 known mutations included beta(41/42), beta(17), beta(IVS2#654), beta(-28), beta(71/72), beta(35), beta(IVS1#5), beta(IVS1#1) and beta(41). Except for the beta(-28) mutation which was found only in the TI group, others mutations were identified in both TM and TI. Co-inheritance of alpha-thalassemia as a phenotype modulating factor was not evident in this study, nor was the presence of the -158 (G)gamma-globin Xmn I polymorphism. Further analysis of the polymorphic (TG)n(CG)m repeats within the IVS2 of the two gamma-globin genes revealed no different proportions of the polymorphic patterns among TM and TI groups of patients either. Our data reveals that in the majority of these Hb E-beta-thalassemia patients, it is very hard to predict the clinical phenotype of the patients from the beta-globin mutations and these secondary genetic modifiers.
PMID: 18951049 [PubMed - indexed for MEDLINE]

But as you can read in bold, it is very hard to predict the physical phenotype.

You've mentioned that you are intermedia. Have you ever had to transfuse and do you know what mutation your other beta gene is?

I haven't had to transfuse and unfortunately I'm not sure about the mutation of other beta gene. I will try to find out and get back to you.
Thank you again for your help!

I want to update you that I had a consult with a Pediatric Hematology doctor and was told that based on this specific mutation, -28A>G, and hemoglobin E trait there is a low risk that baby will have to do transfusion. 

I am really grateful that you took the time to help me. Your site is a great resource for the Thal community.
Thank you again Andy!

I think the reason it is difficult to find information about the  -28A>G mutation is because it is seldom diagnosed because those who carry it have mild symptoms, at the most. HbE by itself is no danger, and this combination does not have a history of producing transfusion dependent patients. It is always difficult to predict the phenotype whem HbE combines with beta thal, but there are many beta mutations that are more or less innocuous. They are noted when a DNA analysis discovers them, but no associated problems are found. I think that this is the most likely case with  -28A>G and hence the lack of comments on the Penn State database.
Best wishes for your baby.

Hi Andy,

I am writing in the same posting as I need the same advice.
I have a kid 6 yrs old with E-beta thalassemia. He has been transfused two times due to fever /infection.
Now my wife is pregnent (11week) and we are going for CVS test nest week.
we got the DNA test for three of us
my self: Hb E
my Wife thal minor: IVS 1-5 (G-c)
my Son E-beta thal : Double heterogygous hbE and IVS 1-5 (G-c),can we predict his condition in terms of severity?
mild/moderate/sever

thanks for your valuable time

regards,
Dip

Predicting the clinical outcome of HbE beta thal is very difficult. The IVS 1-5 (G-c) gene is known to be present in beta thal major, but its presentation when combined with HbE is quite variable, as you have seen with your child. He may well stay the same into adulthood, needing only occasional transfusions. HbE beta thal responds well to even small increases in fetal Hb. Diet and nutrition are important and it would be worthwhile to try wheatgrass, either in juice form or as tablets. Tablets are much more palatable. There is also an adaptation of unknown origin in HbE beta thals, that allows many to avoid transfusions even at lower Hb levels, where transfusion would normally begin. In these cases, transfusion should not begin unless the child is showing signs of severe anemia. If the child is active, healthy and growing, transfusions may not be the proper course in HbE beta thal, so observation is key. Any further children have the same risk of this combination, 25%. Even then, other genetic factors may play a role, so there is no assumption that the condition would manifest the same in two children from the same parents.

Hi Andy,

I have received the CVS report for my wife.

The mutation for all of us are as follows,

My Self:    Heterozygous for HBB:c.79 G>A (E-trait)
Wife:       Heterozygous for HBB:c.92+5 G>C (beta-minor)
Son:        Compound Heterozygous for HBB:c.92+5 G>C and HBB:c.79 G>A (E-beta thal)
Foetal:     Heterozygous for HBB:c.92+5 G>C

So it seems to be the Foetal is also beta minor like my wife.

I have one question suppose in future (may be 5-10yrs down the line) if The Transplant is become a regular cure for the thal, then will my second baby ,be consider to cure the first one, as it itself is thal minor??

Should I go for preserving the chord blood 

Thanks & Regards,
Dip

I would say that bone marrow transplant has become a regular cure for thalassemia and should at least be considered by parents.

If HLA testing shows the fetus is a match, then you should consult with Dr Sodani about how to proceed.
http://www.curethalassemia.org/free-advice-on-bmt/

Hi Andy

Thanks for your reply.

If HLA matched then thal minor is not a problem??
fetus is minor.

regards,
Dipankar

When a thal minor is a donor, the recipient becomes a thal minor.