Hi SYT,
Typically, beta° thal majors need transfusions at an early age, and once diagnosed at or before birth, the usual response is to begin transfusions as soon as the Hb drops significantly, because there is no advantage in delaying transfusion, as low Hb will impair normal development. For a beta° major to have an Hb above 9 at 11 months is unusual, unless some moderating factor such as coinciding alpha thal trait is also present. Since alpha trait has been ruled out, unless the Hb does suddenly drop, as would be expected with beta°, some other moderators might be investigated. These include Xmn I polymorphism and variants in the BCL11A, and HBS1L-MYB genes. These all can cause an increase in fetal hemoglobin to the point where there are known cases of beta° thals who do not transfuse and manifest as thal intermedia. I have no way of knowing if any of these may be present, but the fact is that by this age, most infants have levels of HbF below 10%, which by itself would represent a total Hb of around 1.5% if no other type of hemoglobin was present. Perhaps there is another reason for the persistence of fetal hemoglobin at this age. Over the next few months it will be apparent if any major changes take place and transfusions will begin, but if things continue as is an explanation in terms of a fetal hemoglobin moderator should be explored.
1. I cannot tell you at this point why the Hb hasn't dropped much lower. I have suggested possibilities above.
2. She may require transfusions and if so, it may happen within a couple months. If not, a fetal hemoglobin moderator may be present and transfusions may be delayed longer as with thal intermedia, or, as seen with some recorded cases involving these moderators, transfusions may be only necessary in a transient manner, only when Hb has dropped due to illness. My first reaction on reading your post was that there was no way this child can be phenotyped as anything other than major, but after more reading on the subject, I will say there is some small chance that the current Hb level may be the result of a fetal hemoglobin moderating factor. Because historically, most of these cases have not been reported or analyzed because they had no reason to suspect a genetic thal major, there is no way to know how common these factors appear in thal majors.
3. Possible intermedia? It is possible but under current levels of understanding, it is not common. As I said, because these cases don't manifest physically as major, they have not been recorded for the most part, so I don't think anyone can give a percentage chance. Right now, the child's Hb is what one might expect for a thal intermedia.
4. You have already seen the value of folic acid and this should be continued. My suggestions at this age are few. I would suggest 50-100 IU daily of natural vitamin E complex. I would also suggest monitoring of vitamin D levels and intervention if needed. Both D and E are commonly found to be deficient in thals. Follow a good diet. Avoid high iron foods as long as the child is not transfusing, as the body will try to absorb more iron from diet than is needed. Establish good eating habits at a young age, with emphasis on nutrition and avoidance of highly processed and junk foods. Wheatgrass has also been shown to aid fetal hemoglobin production in some thals, so this might also be considered in some form. As she gets a bit older, I would suggest adding a daily B complex vitamin.
5. In cases of non-transfusing intermedias, changes in facial features are one of the signs that transfusion is needed. The only way to avoid this is by keeping the Hb up. Some patients can manage with Hb levels of just above 7, while others will have more symptoms and changes in bone development unless their Hb is kept higher through transfusions.
If the saying time will tell was ever relevant, it is here. She is at an age where the lack of a drop in hemoglobin level gives some hope, but does not rule out the expected thal major. I would prepare mentally for transfusions, as it is most likely, but be aware of the small possibility of a manifestation of intermedia. Keep in mind that many intermedias also do have to begin transfusions at some point.
This little note got me digging deeper and I do wonder why the word "usually" is used. It is unusual to see beta° phenotype to be expressed as usually. It is normally expressed as "Severe transfusion-dependent beta-thal."
http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=849Codons 41/42
Homozygote
Usually transfusion-dependent