Thalassemia major or intermedia

My son has been diagnosed with compound heterozygous for two beta globin mutations from
both parents,  C.-138 C>T (also known as -88 (C>T) and c.92+5G>C (also known as IVS-I-5 (G->C).  He is entered
in fifth months and doing pretty good. He is active and feeding well and at present his blood level is around 9.5
We have done DNA testing for both of us, result of which are awaited.  Then the doctor will let us know what severity
of disease will be.    However, the doctor have recommended to give him folic supplement with the formula milk.
My question to Mr Andy is that it is thalassemia major or intermedia?  The doctors have not confirmed it as they
also awaiting the blood reports.

The -88 (C>T) mutation is a beta+ mutation and is mild. The IVS-I-5 (G->C) is also beta+ but considered more severe. I would not expect beta major from this combination. The -88 (C>T) mutation makes it more likely that thal intermedia and possibly even a thal minor phenotype may be the result. The current Hb is still good, and most severe cases would already be transfusing. The parental DNA test will be more revealing and I will be interested in the normal Hb level of the parent carrying the The -88 (C>T) mutation.

Thank you so much, Andy
I am glad to read that.   We have given blood sample for all testing including DNA for both of us (both parents).  We gave those sample on 28 February 2013, reports still awaited.   Why they (Labs) are taking too much time don't know.   I pray to ALMIGHTY that your worlds should go correct.   I have another son who is 10 years old and he has thalassemia trait.  He is doing good and hardly we see doctor for him for any ailment.  We both parents have beta thalassemia traits and with the grace of God, we both parents also hardly see any doctor for ourselves. 
We also wish to express our gratitude for your flawless support, contribution, dedication and administrating such a best social organization (thal.com) .  This site is great, all members are great, they quickly respond to the patients/parents.   I am in touch of this site since the day when my son was called for new born baby screening as in his new born baby screening his blood was containing only Hb F.   Hb A or A2 were missing.   Doctor of my son is Dr Giardina of Weill Cornell Medical Collage, New York.  We take our son for check up after every 3-4 weeks. 

Thanks, 

Dr Giardina is very good. It is also a good sign that none of you have problems caused by thal minor, as this does give even more hope that the diagnosis will be intermedia. What I found most interesting is that people homozygous for -88 (C->T), meaning they have two of that gene, have a thal minor phenotype. It appears to be a very mild mutation.

Dear Andy
Thanks a lot.
One more question that I have is that as per report in new born baby screening, the baby was diagnosed with compound heterozygous for two beta globin mutations from both parents,  C.-138 C>T (also known as -88 (C>T) and c.92+5G>C (also known as IVS-I-5 (G->C).  But as per your last message you mention it to be homozygous for -88 (C>T).   Are these both mutation almost same or otherwise ?
My next appointment with the doctor is scheduled on 09 May 2013 and I will also let you
know the outcome of those reports.

Thanks and regards,

No, I mentioned the homozygous -88 (C>T) to demonstrate that the -88 (C>T) mutation is a very mild one. That should lessen the severity of the phenotype when combined with another thal mutation, in this case IVS-I-5 (G->C).

Thank you so much Andy
His blood was Hb F 100% .  No A or A2 was present when he was around 20 days old.
Is this has any link with severity and when does a baby start making other hb ?
Thank for helping us and giving prompt responses. Your response clears our doubt.

Both thal major and intermedia can give a 100% HbF reading at birth. This changes as the baby gets older and between 6 and 9 months, an electrophoresis will show a more clear picture of which hemoglobins are being produced.  Has either parent had problems with anemia throughout their life?

Thanks Andy for the immediate response.
May God bless all patients and families.  Everybody should get God' blessing and cure for the disease.
Actually Dr Andy when my wife was around two months pregnant her hb level was 9 with hb F<1,
HbA 94.4, HbA2 4.7
my hb on July 20, 2012 was 12.4 wih Hb A 91.6, Hb F 2.0, HbA2 6.4.
My son who is 10 years old, his Hb level is 9.2 wih Hb A 93.3, Hb F 1.4, Hb A2 .3
I know these level for we all 3 myself, wife and son (elder) is below normal level. But we never faced any problem and never fell sick for any reason. Even we never get fever.
Andy if my son is intermedia then if any  possibility that he will get some health problem.
Your help is much appreciated.

Thanks
Best regards
Rajiv

Actually Andy I forget to mention that our blood level is not low
due to iron deficiency.
Hope this will help to give a conclusion.

Thanks and regards

Dear Andy
My wife works very hard, she is house wife and in India she worked in the field for agricultural purposes and never faced
any problem with regards to anemia.   I am a serving soldier who served 15 years in the armed forces and never fell sick and never
faced any problem due to anemia.  My elder son has also been quite fine and until now there is no need to see the doctor for any ailment.
In my family and my wife's family there is no thalassemia history.   We both belongs to different states of India.  She is from Rajasthan and I am from Haryana.

Rajiv,

Your Hb is on the low end of normal, which is good for thal minor. From the data I currently have, I suspect you carry the -88 (C>T) mutation. The signs are good that your son will have a more moderate type of thal, but keep in mind that many intermedia patients do transfuse. Were you both also tested for alpha thal in the DNA test? Has Dr Giardina given you any idea of what you should expect in the long term or is she waiting for the test results first?

Dear Andy
Dr Giardina told me that they have received the report on A Globin and the reports on that are good for both the parents.  Nothing abnormal found in DNA for A globin.  When I asked about type of thalassemia she told that there are 10-15% chances that the baby has intermedia otherwise chances are for major as the baby has got two mutation.  Except this nothing told to us.  They are awaiting the complete DNA test report which include B globin and mutation site and likely severity of the desease.   My next appointment with the doctor
is on 09 May 2013, hopefully they will tell us about the lab results/DNA.   I will get a copy of those reports also.  Will convey to you upon receipt.  I have read article on intermedia in this site and have idea.  With the help of you all my dear ones, we will take care of baby with medicines available and the transfusion if needed.  We both parents are also ready to go for transplant if it gives a permanent cure.  For that purpose, we also did swap test for my elder son to check if he is a perfect match for his younger brother or not.  His result also awaited.  They (Hospital) also took blood of the baby for HLA typing. 
At our first appointment the blood level Hb of the baby was 8.6 so they (Drs) were expecting for likely transfusion.  On our 2nd appointment the blood level Hb was 9.6.   We are living with the baby and watching his activities.  He is active and playing  well by moving handing and legs with speed, he is trying to talk, sometime yelling as if he wants to say something and sleeping well.    But one thing seems different is that he likes to take milk when he is tired/likely to get sleep.    When awake don't want to have milk.  In nights he take milk more than to day time especially when he is half sleep and half awake.

Dear Andy
I went to the doctor today with the baby for regular/monthly check-ups.  So far everything is going well.  Baby is doing great. 
His Hb level was 9.8 so nothing to worry about for this time now.  I asked for the lab result.  A globin result they have received and it is
negative, nothing abnormal was found in A globin DNA analysis.  For beta globin DNA results are still awaited.  I am in contact and
they will let me know when the reports are received.  Today I have sent all reports to you on your email id - andy@thalpal.com  for your kind perusal please.  Please tell us if you observe anything that is different from what you have told us so far.
As per the medical authorities it was said that both the mutation are severe (one is beta+ and second is beta0).  So the chances are that
baby is a beta thalassemia major patients who will require frequent medical attention and needed transfusion. 

The one report explains why the parents are tested, as the chromosomes the mutations are on in each parent will make a difference. The child is still so young that it is very difficult to predict from the current status. The parental DNA report will reveal more. As the report says "The genotype-phenotype correlations for beta globin mutations are complex." Often, waiting to see what happens is all that can be done. If the child's Hb holds at a decent level after 6 months, another electrophoresis is often done to get a clear picture.
I think much will depend on how much the C.-138 C>T mutation affects beta globin production.
 
Because there is a good possibility that the child will be transfusion dependent, the parents should prepare themselves for this event. Resist any suggestions that the child get a port, as this is mostly done for the convenience of the hospital staff and does pose risk of infection.