Light form of intermedia β-thalassemia

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Offline Bessie

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Light form of intermedia β-thalassemia
« on: March 25, 2008, 12:30:34 PM »
Hi everybody!
My name is Bessie (32 years old) and I am a new member. For me and my husband it was a big relief to discover this forum!!
Both my husband and I are heterozygous for β-thalassemia. My husband has β-thalassemia trait (CD6-A mutation, heterozygous) and I am a heterozygous carrier for the -101 C>T mutation. Both of us are asymptomatic and receive no iron medication.
Back home in Greece we were told that our child if it inherits both mutations will have mild anemia and may need blood transfusions in case of surgery or pregnancy.
Currently we are in Germany and I am 4 months pregnant!Things though have changed since we decided to verify what we were told back home. After genetic counseling in Germany we were introduced to the term of intermedia thalassemia. The doctor told us that in the case that our child inherits both our mutations it will have a light form of intermedia β-thalassemia. She did not mention anything about blood transfusions and she also stated that there is no need to terminate the pregnancy.
After reading a lot about intermedia thalassemia and how much the phenotypes vary from patient to patient we got very confused and nervous to tell you the truth!
Has anyone come across the term light intermedia thalassemia?
Does it mean what words say?That it will have a light form of thalassemia intermedia?
Could at some point of its life become transfusion dependent?   

Any help will be greatly appreciated!!!
Thank you all in advance!

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Offline Manal

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Re: Light form of intermedia β-thalassemia
« Reply #1 on: March 25, 2008, 10:07:26 PM »
Hi Bessie and welcome to the site :welcomewagon

First i would like you to read the section about thal intermedia in this linl

http://www.thalassemiapatientsandfriends.com/index.php?topic=1575.msg13007#new

Concerning your question i guess it is hard to have an accurate answer for it because sometimes you can have the same genotype in two persons and at the same time each can have a different phenotype depending on many other factors that can affect the thalassemia either directly or indirectly. So i guess no one is like the other even with exact same mutations.

Actually i had the same question concerning my son and Andy had given me a very informative answer that you can read about at this link

http://www.thalassemiapatientsandfriends.com/index.php?topic=1576.0

Please feel free to ask anything and i wish you all the luck in your pregnancy

Take care
manal

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Offline Andy Battaglia

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Re: Light form of intermedia β-thalassemia
« Reply #2 on: March 26, 2008, 05:37:07 AM »
Hi Bessie and welcome to the group,

The CD6-A mutation is classified as a mild beta thalassemia mutation and the -101 C>T  mutation is classified as a silent mutation, which will show only a slight imbalance in beta and alpha globin chains. -101 C>T is found in many cases of mild intermedia. Together, they will technically be described as intermedia but would most likely behave more as a thal minor. I think the doctors are right to not be concerned. Your own mutation is barely discernible by blood tests because it is so mild. I found a nice table at

http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gene.chapter.b-thal#b-thal.T8  and both mutations are listed in Table 5. Mild and Silent HBB Mutations Causing β-Thalassemia. I can't copy the table here but you will find both mutations there.

Quote

Silent mutations, which are characterized by normal hematologic findings and defined only by a mildly unbalanced α/β-globin chain synthesis ratio, result from mutation of the distal CACCC box, the 5' unbalanced region, the polyadenylation signal, and some splicing defects (see Table 5).



Calling this "light" intermedia is more of a characterization than a classification. It is simply a way to describe what is technically intermedia but with few symptoms. Neither of these mutations reduces the beta globin significantly, so hemoglobin levels should be fairly high for an intermedia and most likely more similar to the Hb of a minor.

Manal, although Hb Knossos is a silent mutation because of the normal HbA2 level, when combined with beta thal traits, it can lead to intermedia and even major, just as Lepore and HbE can.  Knossos, in turn, can also be modified by the delta globin gene. In the case of Hb Knossos, the silent classification is because of the normal HbA2 levels. This makes it hard to detect, but like Lepore and HbE, it's outcome when combined with beta thal trait varies depending on the specific beta trait and also other genetic factors, such as presence or absence of hereditary persistence of fetal hemoglobin. In Bessie's case, both genes are known to result in a fairly asymptomatic condition and the combination of the two results in very mild intermedia. Lisa was beta thal Lepore and again, this can range from non-transfusing intermedia to transfusion dependent major. There are often other genetic factors that add or subtract severity. I think we will know much more in the coming years, as I am already seeing an increase of relevant material on the net. Progress in mapping the various genetic combinations is moving fast.
Andy

All we are saying is give thals a chance.

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Offline Bessie

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Re: Light form of intermedia β-thalassemia
« Reply #3 on: March 26, 2008, 01:28:50 PM »
Thank you both Manal and Andy for your quick and very helpful replies!!! :smileblue
Both my husband and I read all the information you have sent us and found answers to our questions!
I came across a publication regarding my mutation and the clinical phenotype of patients when this mutation is co-inherited with other β-thalassemia mutations, which I found very interesting!The authors conclude that interaction of -101C>T with more severe β-thalassemia mutations always resulted in the clinical phenotype of mild-non-transfusion-dependent thalassemia intermedia.

This link to the article is:
http://pt.wkhealth.com/pt/re/bjha/fulltext.00002328-199912040-00005.htm

Thank you again and we'll be in touch
Take care  :flowers

Bessie 
 

 



 

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