13 mo old, questions about trait, minor, & intermediate...

The 13 year old does not appear to be thal. His MCV and MCH are normal. He does appear to be anemic, as his Hb is under 12. Iron tests can tell if this is caused by iron deficiency. The 4 year old looks almost certainly like a thal minor with the low Hb, MCV and MCH and slightly high RBC.

Hi Andy,

Thank you so much for your input, that was what I thought, but wanted to check. Do you know if those with Beta-Thal minor experience chronic or out of the ordinary digestive problems? I have not had these issues and our littlest guy does not, but our daughter (4 year old) has had significant issues beginning when she was around 1 yr, then it subsided temporarily, but has been back for over a year now (symptoms such as very low appetite, constipation beyond what would be considered normal by any means, and possibly reflux - she was prescribed a liquid zantac recently which seems to be helping with pain,but not appetite at all).

If anyone has experience with digestive issues that is not related to transfusions or medications please chime in

Thanks,
S

You bring up a point that we have been hearing about from many people. Bad appetite and stomach discomfort reports in thal minor kids. I can only say that we have heard many similar reports, but there is nothing in any literature that I have seen about thal minor that suggests digestive problems. I am growing to believe that there may be a connection, but cannot explain why it would happen.

Hi Andy,

We had our toddler's appointment today, the analysis was ordered for Alpha-Thal and a complete iron study. We should know more in a few weeks, I was a bit disappointed that the analysis for Beta-Thal or G6PD was not ordered, but we will be patient and see if they find what we need for a definitive diagnosis. The doctor did not think that our daughter had Thal trait, but may have iron def - I decided to let this rest just temporarily until we get our toddler's results back.  I hope she does not have even the trait, but my motherly-sense is saying otherwise.

The reasons I said thal minor for your daughter is that the RDW is not very high, as it usually is in IDA and the RBC is high, whereas it is expected to be low with IDA. An electrophoresis would shed more light on this, as HbA2 is high in beta minor and HbF is measurable, which is normally not be the case in IDA or alpha trait.

Hi Andy,

Based on everything I have read (and goodness it has been a lot, lol), I totally agree with your thoughts on this! After seeing a family doctor today for our oldest son, he felt it was important to do the hemoglobin analysis, iron study, etc. for him to see if he carriers the trait or not - and his CBC results were far better looking regarding Thal possibilities then our daughters were. Unfortunately when the referring doctor called to set up our chart w/the ped hem the doc told us that we would end up with the ped hem that was on duty for that day as an on-call person - like we weren't able to pick the ped hem ourselves (so we did not get to request one of the hem that Eileen Scott had recommended to us, this one is in the same group but was not named to us as recommended). I do plan on following up for our daughters sake and I was ordered an iron study on me as well which I have never had done before. I hope with all of this we will have some concrete answers for all of our children, I would happily go without knowing about myself if we can make sure they are all as happy and healthy as possible!

Thanks so much again

Hi Andy,

My confusion is growing greater here We got the hemoglobin electrophoresis back on our 13 yr old son, on his CBC he did not appear to reflect Thalassemia really at all...his results however were very conflicting to me:

Hemoglobin A1 93.7 L (>96.0%)
Hemoglobin F     4.1 H (<2.0%)
Hemoglobin A2   2.2  (1.8-3.5%)

Erythrocyte count 4.07 L (4.10-5.70)

Hgb 12.3 (12-16.9)
Hct 36.0 (36-49)
MCV 88.3 (78-98)
MCH  30.3 (25-35)
MCHC  34.3 (31-36)
RDW  14.3 (11-15)

Ferritin 25 (7-142)

WBC 6.0 (4.5-13)
RBC 4.17 (4.10-5.70)
Platelet 355 (140-400)

"Red and White blood cell morphology appears unremarkable" they also noted that "Delta Beta Thal...unlikely without microcytosis and the elevation of HbF is not high enough to suggest HPFH". Then they listed possible acquired causes that were pretty scary!

Then on my newest CBC (all my iron levels were within normal range) the only two things really out of range were my RBC at 5.16 (3.8-5.1) and my RDW at 16.5 (11-15). They noted "The most stringent of three thalassemia screening formulae is positive, but the lack of even mild anemia, the presence of anisocytosis, no poikilocytosis as usually seen with beta-thal, and the low-normal ferritin level militate against thalassemia-minor. If further testing is clinically indicated, the Alpha-Globin common mutation analysis...would be helpful".

If my children have presence of Fetal Hgb which is found with Beta-Thal and I don't have Beta-Thal then there father must? or is it possible that I might just be a carrier and had it show up only during pregnancy?

Oh boy, this is not just a simple diagnosis journey is it, lol!

Thanks so much,
Sarah

Hi Sarah,

The HbF level is puzzling. The delta beta carrier possibility almost makes sense, as the microcytosis can be very mild, but even then it normally will result in MCV at the low end of normal, and your son's MCV iis right in the middle of normal. It could be possible that a benign beta variant is present. The scarier reasons for a rise in HbF should be noted by observations about the blood or the white blood cell count, and there is nothing seen here. The WBC is completely normal and that is very important as it rules out CML. The combination of alpha and beta in your son does seem unlikely because the HbF is higher than would be expected, although a combination of alpha trait and delta beta might be a possibility. I think yuo have probably reached the point where a DNA analysis might be the only way to get a definite answer on anyone involved.

Hi Andy,

Thank you for your thoughts on this, we are still awaiting our toddler's alpha results and then we will go from there. I do think all of our children will need to have the DNA testing done, if for no other reason, it will inform them for decision they make as adults and provide them with some solutions to keep in better health!

Thanks

Hi Andy,

Results are in for the alpha deletion test, it is negative for 7 common deletions (guess they did not do the test for mutations). At this time the only advice given was to follow up with reg doc at next checkup to recheck iron levels.

I am at a loss on where to go from here. Should I follow up with a hematologist for our older son and see if we can get answers for his elevated HgbF...? I feel blessed that we have at least eliminated one possible cause of symptoms our little one has had, but sooo frustrated that we have no more answers than we did over a month ago.

If G6PD was an issue, would that have shown up on either the electrophoresis or the alpha deletion test?

Thanks,
Sarah

I just wanted to give an update on our son...it has been quite a while.

Our son developed a palpable lump on his right collarbone (no trauma, fractures, etc. in the area so quite puzzling). Our first question was if it was somehow related to his true iron anemia or if it was related somehow to his Beta-Thal minor diagnosis (even though we know it should not cause this if it is truly the minor state).

After multiple xrays, an MRI w/out contrast, and landing at the wrong pediatric surgeons office...we got regrouped and sought a pediatric ortho surgeon. At this time it appears that he has an exstosis of the clavicle (which could be a symptom of several conditions related to bone dysplasias and bone lesions) - no signs of anything malignant and no signs of cyst or other abnormal tissue. At this time it appears to be made of un-mutated bone and bone marrow...he has had the lump for about 4 months now and it has only gotten slightly larger in this time. It was recommended at this time to wait 3 months and have new images taken and then go from there. In the meantime we are taking him to a neurologist to try to out rule some issues like neurofribromatosis or other types of anemia that are related to cafe au lait spots (he has more than 6).

Has anyone had bone issues with a Thal-minor state? My confusion continues on all of this and I sometimes wonder if the Beta-Thal is more responsible or less responsible than our family thinks it may be at times with the other issues he is having.

Best wishes to everyone, hope all is well

There is a possible relation to thalassemia. I would suggest showing this article to your doctor, as it does explain why bony growths may occur in thalassemia, even minor. Although the article refers to changes in the mouth, it also mentions that the expansion could also be seen in the hand and wrist, and that theoretically this could take place in every bone. There may be a connection to any anemia.

http://scialert.net/fulltext/?doi=jms.2007.923.925&org=11

The radiographic findings described in our case might be added to the well-known hair-on-end lateral cephalometric x-ray appearance and macroscopic maxillary enlargement on head and neck diagnostics (Hollar, 2001; Weel et al., 1987). The medullary expansion due to increased production of erythropoietin could be seen in the radiograph of the skull and hand wrist (Murphy et al., 2002). This appearance considered to be apart from the Thalassaemia a general radiographic sign of severe anaemias such as sickle cell disease (Forbes and Jackson, 2003). As far as we know, the dental panoramic tomography was not reported in the literature as an investigation for examining the quality and quantity of bone in patients with Thalassaemia. Our suggestion is compatible with that of Tyler et al. (2006) concluding that skeletal manifestations may be seen theoretically in every bone. Therefore, the mandible may be included in the process of biochemical changes based on erythropoietin function. The centers of maxillary bone overgrowth, at this case report, seem to be located between the canines and premolars bilaterally indicating the possible location of the expansion origin (Fig. 3). In cervical spine, platyspondyly or bone in bone appearance did not appear in panoramic tomography.

Thank you Andy, I will print that and share it with his doctors! Is there a test or measure of erythropoietin function? Is it the sedementation rate or ESR? We were discussing the other night, among family, that it is odd to us that no one has done a simple chemical panel on our little one, he has had all these CBC's, and more in-depth tests, yet not a single chemical workup since he was in the NICU right after birth...I plan on requesting one, while we dig for deeper answers I don't think we should avoid what may potentially be some obvious answers (one can hope, lol).

Thank you again

I was told my whole life I had Thal Trait until I got pregnant at 35 and they did testing and told me I was Intermedia!
Im 44 now

Sarah,

There is a blood test for erythropoietin. You can read more about it at http://www.medicinenet.com/erythropoietin/article.htm
It is not the same as the ESR test.

Joanne,

Intermedia is something of a vague status. Most thal intermedias have two defective beta genes, but they are not as severely affected as in major. Some are intermedia because they would normally have a more severe phenotype, but they also carry alpha mutations and that will moderate beta thal so it is not as severe, because there will be a closer balance in alpha and beta globin produced, because both sets of globin genes are affected. And there are some who have only one beta gene affected, but is it a dominant gene and even though it looks like minor, some have to transfuse. Since there are hundreds of different beta mutations and deletions, there is a wide range of possibilities when two of them combine in an individual. Have you ever had DNA testing done to determine which beta and possible alpha thal genes you carry? Your Hb is high for an intermedia, but your excess iron absorption has been that of one with a much lower Hb level.  The more I hear reports from thal patients, the more I realize that the accepted knowledge about thal often varies greatly from what real people experience.