Again!

hi to all:

fantastic news... lauryn went to her hemo today and her hgb was 10.3! it went up a point fom 2 weeks ago.

even though she had a massive ear infetion (and is still not herself..runny nose croupy cough etc...).
she lost 12 ounces, but the md attributes that to her getting over being sick. her ears are clear and her chest is also clear. her heart sounds fine.all looks good.
the md is unsure as to why she is stabalizing after 6 weeks from the first tx. he says the donor blood should be gone by now...

Her speen is only 1/2 cm(a fingertip).it was 3 cm's 2 weeks ago. the next step is in 2 weeks, do her regular labs, and assuming she will still be in the 10's, wait another month for her second transfusion!

the mds only logical theory is when she was 7.6 at the time of  the first transfusion, she must've had a virus or "bug" that we did'nt detect, and that is why she dropped and needed her blood. he guesses that after the transfusion she stabalized and is now holding her own again, so to speak.

we got the DNA results: she is definitley Thal major.

its VERY complicated to explain but according to the md, lauryns mutation is very unusual.

one of us (husband or I) carry the nt168 gene
and the other nt365+45

the results say:

IF NT168C-T AND NT365=745C-G ARE ON OPPOSITE CHROMOSONES, THE MOLECULAR RESULTS WOULD BE CONSISTENT WITH BETA THALASSEMIA. TAREGETED TESTING OF THE PATIENTS PARENTS WOULD CONFIRM THE ORIENTATION OF THESE SEQUENCE VARIATIONS.

NO EVIDENCE OF THE 619BP DELETION OF THE B-GLOBIN GENE IDENTIFIED.


if i remember correctly, the dr says lauryn has 2 diff. types of defective genes that equal thal major. she doesnt have the TYPICAL COMMON defect. I think he said our odds were even greater with the genes that were affected.

i guess she belongs in the next X-MEN movie? 

Hi Christine,

It's great to hear that Lauryn is doing great and has recovered from her ear infection. The DNA reports can be pretty technical We also had some trouble understanding the DNA report when it came in ... the only thing that we surmised was that I had a bad gene, my wife had a bad gene and our daughter inherited both the bad genes ..... and so ended up being b-Thal Major.

Hoping that Lauryn keeps up her Hb level at the time of her next check-up.

Hugs to Lauryn.

Take care,

Bostonian

Hi Christine

Good to know where we stand. Very happy to know that Lauyrn is fine. Let's hope she will maintain her HB as long as possible.

Keep it up

Manal

Hi Christine,

That's really good that Lauryn is maintaining her Hb.

I hope her special mutation increases the Hb. every now and then like she is doing now and keeps postponing the transfusions.

Take care, Peace!

andy?

what are your thoughts,please?

Hi Christine,
Thats great to hear lauryns hb went up! take care of lauryn all the best!
 

Hi Christine,

It is true that Hb can drop with infections so that may explain that original drop. Some bacterial infections can actually cause hemolysis, the breaking down of red blood cells, although normally symptoms would be noted. Factors such as temporary dehydration, which is not uncommon in infants, can also play a role in lowered Hb. Whatever the cause in Lauryn's case, it did seem to be short term.

From what you've been told it sounds like the two genes work as modifiers of what each other does, leading to thalassemia major. I would like to know more about Lauryn's DNA testing. Were you told which chromosomes these genes occur on? Before you asked for my input I had already spent hours trying to find mention of these genes, and at best I found mention that they exist, which is often the case with the specific thal mutations. Their existence is cataloged but not much information about effects is available. However, DNA testing is how the effects of these deletions will also be eventually cataloged. If you have any other information from the DNA tests, such as anything that contains the term, IVS, let me know. For example, IVS2-745C>G.

we got the DNA results: she is definitley Thal major.

its VERY complicated to explain but according to the md, lauryns mutation is very unusual.

one of us (husband or I) carry the nt168 gene
and the other nt365+45

the results say:

IF NT168C-T AND NT365=745C-G ARE ON OPPOSITE CHROMOSONES, THE MOLECULAR RESULTS WOULD BE CONSISTENT WITH BETA THALASSEMIA. TAREGETED TESTING OF THE PATIENTS PARENTS WOULD CONFIRM THE ORIENTATION OF THESE SEQUENCE VARIATIONS.

NO EVIDENCE OF THE 619BP DELETION OF THE B-GLOBIN GENE IDENTIFIED

Christine,

Lauryn amazes me with her stable hemoglobin, which is a good sign. The lesser the transfusion requirement the better it is.

Do you know what type of DNA test was done? Was it for Alpha Thal or Beta Thal?

beta thal, i believe narendra

johns hopkins hospital did the dna test.

the other part of the results say:

FULL SEQUENCING OF THE CODING REGIONS  OF THE HBB (BETA GLOBIN) GENE AND ANALYSIS FOR 619BP DELETION INDENTIFICATION OF MUTATIONS ASSOCIATED WITH B-THALASSEMIA AND B-GLOBIN STRUCTURAL VARIANTS.

POSITION   NORMAL   PATIENT

NT20            C            C/T
NT168          C            C/T
NT365=745   C           C/G

INTERPRETATION:

NT20C-T :NOT A REPORTED MUTATION OR POLYMORPHISM, BUT WE HAVE SEEN THIS VARIATION IN SEVERAL FAMILIES ON THE SAME CHROMOSONE AS NT365=745C-G.THE CLINICAL SIGNIFICANCE OF THIS VARIATION IS UNCERTAIN.

NT168C-T(Q39X):PREVIOUSLY REPORTED NONSENSE MUTATION

NT365=745-G(INTRON 2):PREVIOUSLY REPORTED SPLICING MUTATION

there is a reference on the paper as well:

http://globin.cse.psu.edu/html/huisman/thals/beta/codon.39.(c-@t).cag(gln)@TAG

NT20   

Christine,

Both of these mutations cause aberrant messenger RNA to be produced, resulting in defective beta globin protein chains that damage the red blood cells. Of great interest is that there has been much research into correcting this, as this mutated mRNA is at the root of many genetic diseases.

From http://www.pnas.org/cgi/content/abstract/97/17/9591

Mononuclear cells from peripheral blood of thalassemic patients were treated with morpholino oligonucleotides antisense to aberrant splice sites in mutant beta -globin precursor mRNAs (pre-mRNAs). The oligonucleotides restored correct splicing and translation of beta -globin mRNA, increasing the hemoglobin (Hb) A synthesis in erythroid cells from patients with IVS2-654/beta E, IVS2-745/IVS2-745, and IVS2-745/IVS2-1 genotypes. The maximal Hb A level for repaired IVS2-745 mutation was approx 30% of normal; Hb A was still detectable 9 days after a single treatment with oligonucleotide. Thus, expression of defective beta -globin genes was repaired and significant level of Hb A was restored in a cell population that would be targeted in clinical applications of this approach.

These thal mutations are mainly Mediterranean in origin and are quite different from many other thal mutations. While this research holds promise for restoring normal hemoglobin in people with these types of mutations, it would not be useful for thal mutations where beta hemoglobin isn't produced. I have heard before that thalassemia is actually many different disorders under one label and this is a perfect example of what this means. In thalassemia caused by these mutations, it is actually an mRNA defect in the hemoglobin rather than an inability to produce beta hemoglobin.

Interestingly, with this type of thal, the presence of alpha thal trait can actually be a moderating factor, leading to a less severe thalassemia.

Christine,
     So glad to hear that Lauryn's hemoglobin has gone up. She may have major, but she is holding her own on the hemoglobin front! She's a tough cookie. I don't know why they don't run alpha testing when they test for beta. Just get it all done so there's no doubt. Anyway, it sounds like Lauryn has a rare kind of mutation. I wish you and her the best in the upcoming days. Let's hope she keeps that hempglobin up for as long as possible. Jean 

hi andy!!!

im so sorry. i am confused. can you explain what you mean is lauryn one of the "lucky thals"?. i dont understand what her mutations are or how they differ from regular thals??

is this good?> 
should i be happy?

 why didnt her doctors tell me this?

 what is thal A trait?

Hi Christine,

Alpha thalassemia is the other thal that is most commonly found in east Asians. In some cases, when it co-exists with beta thal it can act as a modifier, lessening the severity of the thal. From Lauryn's genetic background, it is highly unlikely that she is also an alpha thal carrier.

With the type of mutation Lauryn has, her body would be able to produce normal hemoglobin if the mRNA was not aberrant. The subject of this research that I mentioned is to correct this mRNA defect. Because this defect is also responsible for many other genetic problems, there is much research being done on how to correct the lack of normal mRNA. If this research succeeds it will have many applications including providing a cure for this type of beta thal. It would be of no use to the many other thals whose thal is not mRNA related. There are many reasons that the beta gene does not produce its part of the hemoglobin and all these varying mutations and deletions are lumped under the category of beta thal even though there are substantial differences in the way the mutations affect the production of hemoglobin.

The doctors may not be aware of this research as it is only in the research stage and not available as a treatment. It is however, a very promising area of research and may eventually provide a cure for this type of beta thal. It is reason for cautious optimism and developments in this area should be followed.

so what your saying andy... is that her thal major is a lesser form?

this kid has had only 1 transfusion in 9 months. she is showing no signs of low hemoglobin as far as im concerned. she eats and drinks like a horse!!!

she is also very happy.

wouldnt you agree that intermedia is based on the frequency and need of tx's?

could she be classified as intermedia,even though her dna proves major?