Newly diagnosed Thalassemia Intermedia

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Newly diagnosed Thalassemia Intermedia
« on: January 29, 2015, 12:56:35 PM »
DNA test has confirmed my daughter has Beta Thalassemia Intermedia. i have spoken to Eileen Scott at the Cooley's anemia foundation. still coming to terms with this diagnoses. she is 13 months old currently and her HB was 11.3 in November. i have Beta Thalassemia Minor and my husband is believed to have the HPFH trait.

 compound heterozygous for HPFH 3 / codon 15 β0-thalassemia mutation

can someone please help me get some insight into what the above means?

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Offline Andy Battaglia

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Re: Newly diagnosed Thalassemia Intermedia
« Reply #1 on: January 30, 2015, 08:09:20 AM »
Quote
compound heterozygous for HPFH 3 / codon 15 β0-thalassemia mutation

As long as this diagnosis is certain and it is HPFH and not delta beta thalassemia (and a DNA test is considered conclusive and would be able to tell the difference), this should be a mild phenotype where HbA is replaced by HbF, posing no risk to the child.

Please see the chart on page 4 of the attached file. As you can see, HPFH poses no risk in any combination.
Andy

All we are saying is give thals a chance.

Re: Newly diagnosed Thalassemia Intermedia
« Reply #2 on: January 30, 2015, 12:37:42 PM »
Andy,

her Hb F level is almost 100% and Hb A2 is 1.1%. the genetic counselor also said that my daughter has a  "mutation and a deletion in the HBB gene". can you elaborate on that please?

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Offline Andy Battaglia

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Re: Newly diagnosed Thalassemia Intermedia
« Reply #3 on: January 30, 2015, 05:48:17 PM »
Yes, there will be no HbA, as there is no gene that can produce it. With codon 15, the beta zero is the result of an amino acid substitution and not a deletion, so the gene is there but useless, so one gene has no function due to the codon 15 mutation. In HPFH, the beta gene is fully deleted, and although the mechanics are not perfectly understood, that allows the gamma gene to fully express, as it does before birth, replacing the function of beta globin with gamma globin, which combines with alpha globin to form fetal hemoglobin. In HBPH, this function is typically enough to provide an Hb level that is no worse than thal minor. The HbF is also distributed more evenly in blood cells, providing a more stable condition.

The reason I mentioned delta beta thalassemia, is because they are very similar genetically and sometimes mistaken for each other, but a DNA analysis is able to differentiate between the two. So, as long as this DNA test was accurate, and there is no reason to believe otherwise, as long as it was done at a true lab and not at an online company like 23andme, the results should be viewed with confidence. I think an Hb of 11 at 13 months is also a sign that you are not dealing with any severe phenotype.

To summarize, the codon 15 is a mutation while the presence of HPFH 3 shows that the beta and delta genes are fully deleted in that gene cluster. Function is replaced by the gamma gene. Your child will always have close to 100% HbF. The cluster that contains the codon 15 beta gene still has a functioning delta gene. The globin produced by the delta gene combines with alpha globin to produce HbA2, hence the small percentage of HbA2 present.
Andy

All we are saying is give thals a chance.

Re: Newly diagnosed Thalassemia Intermedia
« Reply #4 on: January 30, 2015, 05:53:39 PM »
DNA test was conducted at Boston university. DNA report specifically mentions HPFH. we are planning to have my husband also do a DNA test to confirm that it is HPFH indeed. for the time being her doctor is keeping her diagnoses as beta thal intermedia. are there questions i should specifically ask him?

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Offline Andy Battaglia

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Re: Newly diagnosed Thalassemia Intermedia
« Reply #5 on: January 30, 2015, 06:18:36 PM »
Because both beta globin genes are affected, it is technically an intermedia genotype, but it manifests as a fairly normal phenotype because there is a sufficient amount of gamma globin being produced to maintain a good Hb level. It is normal to test the parent to confirm what has been shown by the DNA analysis of the child. As long as your husband's test comes back as positive for HPFH, there should be no health concerns. If they are unable to fully explain the scenario, contact Boston Children's as it has one of the top thal centers in the US.

Andy

All we are saying is give thals a chance.

Re: Newly diagnosed Thalassemia Intermedia
« Reply #6 on: January 30, 2015, 06:45:01 PM »
ANDY,

attached is the DNA test results that i forgot to attach previously.

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Offline Andy Battaglia

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Re: Newly diagnosed Thalassemia Intermedia
« Reply #7 on: January 30, 2015, 08:42:06 PM »
Thank you for the report, as it does clarify some things. The Indian version of HPFH does have a difference from the other types of HPFH, and it does narrow the codon 15 down to a specific mutation (there are 3 different codon 15 mutations known).

The cases of 4 patients are mentioned as having a more intermedia level Hb. This report is 14 years old, so the question that needs to be asked of the hematologist is this, is there anymore recorded history of patients with this combination of HPFH and codon 15 that would show how more than these initial 4 cases, so you can know what phenotype to expect as the child grows?
Andy

All we are saying is give thals a chance.

 

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