How Was Your Intermedia Diagnosed?

Manu

Please go thru this to check all the thal variants.

Hi Bharat,
Has all possibility of you carrying any thalassemia mutation been ruled out? Have you also been tested for other non thal varaitons, like the lepore trait or Hemoglobin E? If none of these are a possibility and only the mother carries the trait, your child cannot be a major. Both parents have to be a carrier to be a major. Your child would have one thal Hb gene and one regular Hb gene, making the child a minor, the same as when a major has a child with a non carrier. And most of the moms in this group who are majors will tell you their kids are normal minors.
 However, if you read the recent posts in this thread by MicheleKH you will see a different story. This is similar to what we heard from Barry at our previous site. 

http://groups.msn.com/ThalassemiaPatientsandFriends/general.msnw?action=get_message&mview=1&ID_Message=3394

And this is why the defintion of intermedia is so vague. They tell us about intermedias who have only one thal gene. Cicci recently told us that the doctors said his daughter could be an intermedia like he is, even though the mom is not a carrier. If a person with only one thal gene can be an intermedia and require transfuions, then our definitions need serious revision. I think the problem lies in that the condition is relative to the extent of mutation on the gene and also in the cases where the thal gene is a dominant gene, as marientina brought up.

This has also been in our old discussions concerning the varying severity of minor. Some people are very much worse off than others who supposedly have the same condition. I think widespread studies on the actual severity of the gene mutation in thals would be very helpful in understanding the these wide variations. Is it possible to know through genetic tests how severe the variation is in one's genes and counsel prospective parents accordingly?

I think most people will tell you that your child will be a minor. These other cases happen, but are not typical. Does anyone know if it is possible and also accessible for people to have gene testing done for thal genes? It seems that this knowledge could be useful in many ways.

I think some of the moms out there can tell you about their pregnancies and what is required as far as transfusions and chelation.

We first found out that my son had Thal when he was just 4 years old. At the time I was pregnant with my daughter. After several blood tests the doctors realized that Dimitri had Thal minor but something else was also interfering with it causing the ferritin to stay really high. We knew his father had Thal minor so they kept looking to me to find anything. I do not have thalassemia and 3 DNA tests done on me lead to 7 years of studying Dimitri and what was interfering and causing him to be more sick. When Dimitri was 6 years old a Doctor in Arizona, USA did a bone marrow aspiration on him and found his Sideroblastic very high levels. At the time I didn't understand what Sideroblastic was. The report was sent back to Dimitri's primary doctors in Greece, and then we began to talk and understand more about Sideroblastic and how it was causing his body to react as a Thalassmia Intermedia. In time I changed Dimitri's Primary doctor to the doctor here in Utah, USA. About 2 months ago he did another Bone Marrow aspiration on Dimitri, but the strange thing he did not see the Sideroblastic ring on his blood this time and is having them re-test it. The thing is with the report from the doctor in Arizona and the way Dimitri’s blood test are he insists that we get treatment for him as a Thal Intermedia to prevent any more damage to the body. They believe that I am a carrier of Sideroblastic. My daughter still has yet to be confirmed if she has the same condition as her brother.

Hi,
I am a 44 year old that was diagnosed with Thal Minor in 1974(?), around 1986-I heard the term Thal Intermediate for the first time.  I had a spleenectomy/cholestectomy in 2004.  In 2005, with the birth of my second child, I was diagnosed with Portal Vein Thrombosis/Messenteric Ishcemia.  I was placed on Hydrea without any changes to Hgb or Platelet counts.  I was on Coumadin for several years, and then was told the chance of recurrent clotting was slim.  They mainly blamed it on my 'condition' and being pregnant.  I was off anticoagulants for about 5 months and developed a large blood in my cecum resulting in a right hemicolectomy and removal of the illeocecal valve.  After 22 days in the hospital and now a lifetime of GI problems, my Hbg are lower than they have been.
I was told I am heterozygous for the codon 39 CAG>Tag or Gln39term Beta Thalassemia mutation.
Also heterozygous for the a-globin gene triplication of the anti-4.2 type ( aaa anti_4.2/ a a )......Whatever that all means, but was told this confirmed my Thal Intermediate status.

Here a copy of my lastest labs----Love the Hgb of 7.2---yes, tired, short of breath, all the usual.  I have developed quite a few antibodies to blood from intermittent transfusions.  Now, awaiting further phone calls from doctors regarding transfusion dependency.  Any thoughts are respected.

Linda


LAB:
Recent Results (from the past 72 hour(s)) CBC (WITH DIFF) Component Value Range • WBC 6.5 4.0 - 10.0 (x10(3)/mcL) • RBC 3.13 (*) 3.93 - 5.22 (x10(6)/mcL) • Hemoglobin 7.2 (*) 11.2 - 15.7 (gm/dL) • Hematocrit 23.7 (*) 34.0 - 45.0 (%) • MCV 75.7 (*) 79.0 - 94.0 (fL) • MCH 23.0 (*) 26.6 - 32.2 (pg) • MCHC 30.4 (*) 32.0 - 36.5 (gm/dL) • Platelets 832 (*) 145 - 370 (x10(3)/mcL) • RDWSD 77.9 (*) 35.0 - 46.0 (fL) • RDWCV 30.9 (*) 10.9 - 14.4 (%) • MPV 11.3 9.0 - 12.0 (fL) COMPREHENSIVE METABOLIC PANEL (NON-FASTING) Component Value Range • Glucose Lvl 79 60 - 199 (mg/dL) • BUN 11 8 - 18 (mg/dL) • Creatinine <0.20 (*) 0.70 - 1.20 (mg/dL) • Sodium 137 135 - 145 (mmol/L) • Potassium 3.5 3.5 - 5.0 (mmol/L) • Chloride 106 98 - 107 (mmol/L) • CO2 21 (*) 22 - 31 (mmol/L) • Anion Gap 10 5 - 15 (mmol/L) • Calcium 8.8 8.5 - 10.5 (mg/dL) • Total Protein 7.1 6.4 - 8.3 (gm/dL) • Albumin 4.0 3.2 - 5.2 (gm/dL) • AST 51 (*) 0 - 30 (unit/L) • ALT 28 0 - 30 (unit/L) • Alk Phos 69 40 - 104 (unit/L) • Total Bilirubin 5.4 (*) 0.2 - 1.3 (mg/dL) • Bili, Direct 0.2 0.0 - 0.3 (mg/dL) • Estimated GFR >60 >=60 IRON AND TIBC Component Value Range • Iron 227 (*) 30 - 150 (mcg/dL) • TIBC 274 250 - 450 (mcg/dL) • Iron Saturation 83 (*) 20 - 50 (%) RETICULOCYTE COUNT Component Value Range • Retic Ct % 8.4 (*) 0.5 - 2.4 (%) • Retic Ct Abs 0.280 (*) 0.027 - 0.095 (x10(6)/mcL) • Immature Retic% 49.0 (*) 2.3 - 15.9 (%) • Reticulated Hgb 22.0 (*) 28.8 - 38.9 (pg) • Plat Immature % 2.8 0.0 - 7.4 (%) HEMOGRAM Component Value Range • WBC 10.8 (*) 4.0 - 10.0 (x10(3)/mcL) • RBC 3.29 (*) 3.93 - 5.22 (x10(6)/mcL) • Hemoglobin 7.1 (*) 11.2 - 15.7 (gm/dL) • Hematocrit 24.6 (*) 34.0 - 45.0 (%) • MCV 74.8 (*) 79.0 - 94.0 (fL) • MCH 21.6 (*) 26.6 - 32.2 (pg) • MCHC 28.9 (*) 32.0 - 36.5 (gm/dL) • Platelets 612 (*) 145 - 370 (x10(3)/mcL) • RDWSD 85.8 (*) 35.0 - 46.0 (fL) • RDWCV 30.4 (*) 10.9 - 14.4 (%) • MPV Not Measured 9.0 - 12.0 (fL) DIFFERENTIAL, MANUAL Component Value Range • Neutrophil % 59 34 - 71 (%) • Lymphocyte % 15 (*) 19 - 53 (%) • Monocyte % 18 (*) 4 - 13 (%) • Eosinophil % 5 0 - 7 (%) • Basophil % 1 0 - 2 (%) • Myelocyte % 1 (*) 0 - 0 (%) • Promyelocyte % 1 (*) 0 - 0 (%) • Neutrophil Abs 3.8 1.5 - 6.3 (x10(3)/mcL) • Neutr Abs (ANC) 3.83 1.50 - 6.30 (x10(3)/mcL) • Lymphocyte Abs 1.0 1.0 - 3.6 (x10(3)/mcL) • Monocyte Abs 1.2 (*) 0.2 - 1.0 (x10(3)/mcL) • Eosinophil Abs 0.3 0.0 - 0.5 (x10(3)/mcL) • Basophil Abs 0.1 0.0 - 0.2 (x10(3)/mcL) • Myelocyte Abs 0.1 (*) 0.0 - 0.0 (x10(3)/mcL) • Promyelo Abs 0.1 (*) 0.0 - 0.0 (x10(3)/mcL) • nRBC % 301 (*) 0 - 0 (%) • Tot Diff Cell Ct 100 • Plat Estimate Increased • RBC Morphology Abnormal • Macrocytes gtr than 10 (/HPF) • Microcytes 1-5 (/HPF) • Hypochromia Marked • Polychromasia Present (>5/HPF) • Tear Drop Cells 1-5 (/HPF) • Target Cells 1-5 (/HPF) • Schistocytes 1-5 (/HPF) • Burr Cells 1-5 (/HPF) • Spherocytes 1-5 (/HPF) • Stippled RBCs Present (>1/HPF) • Howell-Jolly Bdy Present (>1/HPF) • Pappenheimer Bdy Present (>1/HPF) • Giant Platelets Less than 1 (/HPF) • Platelet Clumps Present • nRBC Abs 19.530 (*) 0.000 - 0.012 (x10(3)/mcL) SCAN, PERIPHERAL BLOOD Component Value Range • Plat Estimate Increased • RBC Morphology Abnormal • Macrocytes gtr than 10 (/HPF) • Microcytes 1-5 (/HPF) • Hypochromia Moderate • Polychromasia Present (>5/HPF) • Tear Drop Cells 1-5 (/HPF) • Target Cells 6-10 (/HPF) • Schistocytes 6-10 (/HPF) • Burr Cells 6-10 (/HPF) • Spherocytes 1-5 (/HPF) • Stippled RBCs Present (>1/HPF) • Howell-Jolly Bdy Present (>1/HPF) • Pappenheimer Bdy Present (>1/HPF) • Giant Platelets Less than 1 (/HPF) • Platelet Clumps Present NUCLEATED RED BLOOD CELLS Component Value Range • nRBC % Auto 276.6 (*) 0.0 - 0.2 (%) • nRBC Abs Auto 29.820 (*) 0.000 - 0.012 (x10(3)/mcL)

 Hi Linda,

I was told I am heterozygous for the codon 39 CAG>Tag or Gln39term Beta Thalassemia mutation.
Also heterozygous for the a-globin gene triplication of the anti-4.2 type ( aaa anti_4.2/ a a )......Whatever that all means, but was told this confirmed my Thal Intermediate status.

This combination of genes varies in severity from a mild phenotype to a severe expression. It is classified as thal intermedia. Basically, the triplicate alpha gene produces too much alpha globin and the beta° gene results in less beta globin being produced, so there is a great imbalance. The result is intermedia. Yours has progressed with age, very much like beta thal intermedia often does. Whereas a beta intermedia might benefit from trying to raise the fetal hemoglobin (HbF) level, by using hydroxyurea or natural products like wheatgrass, raising HbF has a negative effect on those with your gene combination, so there should be no attempt to raise HbF.

What I have heard from thal intermedias in their 40's and older, is that once they start transfusing, they wish they had started sooner, because it made a huge difference in the quality of their lives. There is a trade-off because it does then require compliance with chelation, but most do feel that it is worth it so that they can carry on with life. However, you should also realize that at your current Hb level, your body is going to absorb more iron than it needs, and you may eventually require chelation to remove the iron. Your iron levels already show signs of this happening, as they are higher than normal, but not in an unsafe range. I suspect these levels will rise if your Hb remains as low or lower than its current level. Technically, transfusions are ordered when there are two consecutive Hb tests under 7. You are very close to this now. If no improvement is shown, I would recommend transfusions. Your Hb is too low for you to physically cope with life, and you have to judge this by your own symptoms. Others may manage with an Hb in the low 7's, but many intermedias cannot have anything resembling a normal life at that level. If you do decide to transfuse, after about 10 transfusions, chelation usually starts. These days, the oral drug, Exjade will be the most likely chelator. If it comes to this, we will have some tips about starting on Exjade that can make it much easier to tolerate.

If you have not had your vitamin D level tested, get it done. Deficiency is extremely common and is a factor in osteo disease. Large doses of D are often necessary to reverse deficiency and it is especially common in thals. Deficiency also adds to tiredness, fatigue and depression.

Thanks.  I am starting transfusions this coming week.  I have had a complete endocrine work up and have been on High dose Vit D for 4 months.  I do have Osteopenia, so I know the Vit D level is important.  I also take Vit B 12 injections once a month due to the right hemicolectomy.  I am ready for the transfusions, as I know I try to have a normal quality of life, but am too exhausted to enjoy it.  Thanks for everything.
Linda

The classification of thalassemia intermedia has a somewhat vague defintion that has changed over the years and continues to change. I have seen defintions that say it is a two gene thal and others say it can include one gene thal. The symptoms also cover a wide range. Mostly, it seems that the defintion is based on one's condition as a child, and that condition can change dramatically over time as one ages. As adults, some intermedias transfuse and chelate at or close to the same rate as majors. Some never need to transfuse.

I would like to see what you have to say about how you were diagnosed as an intermedia, at what age, and if you have transfused, and if so, how often do you transfuse? Also, for intermedias who chelate, have any of you had to use an iron chelator like desferal, even though you have never transfused?
When you were diagnosed, what was the diagnosis based on? Do you know what factors or criteria were used to determine that you were intermedia?

I know it's a lot of questions, but if you can answer any or all of them, it would be a great help to those who are trying to determine what their own classification of thal is.

My daughter was diagnosed at age 13 mos with beta thal minor the old name for intermedia.....Now at 29 she is undergoing alot of transfusions she was treated the best way they knew how for the time her HB runs very low all the time 4.6 so they keep pumping her up and talking about a spleenectomy. They requested my ex husband and I be tested which threw us for a loop I don't understand I am not a B thal trait and her dad is not a B thal trait carrier how can this be? any help would be useful Doctor is requesting another test DNA stating the 11th cromasome is affected somewhere but can't find it. So he is wondering something he doesn't dare tread on. So if you have any ideas it would help thanks

A proper diagnosis is required. A DNA analysis is the only sure way to determine what affects your daughter. The diagnosis of thal minor was never correct. Without any test results, I cannot comment much, other than to say if nothing is found on chromosome 11, HbH disease (alpha thalassemia) which affects chromosome 16 should be investigated. If both parents have been tested and beta carrier is ruled out in both, then alpha must be considered. Did you and your ex-husband both have the hemoglobin electrophoresis test?

Is it possible to be Thal Intermedia and have a Hb between 11-12.5??

Is it possible to be Thal Intermedia and have a Hb between 11-12.5??

Good question. I am an Intermedia and I do extremly well, but my Hb is hardly ever over 10. I take daily supplements and exercise 3-5 days a week. Also taking L-Arginine and L-Carnitine daily.

It is not likely, unless there are other moderating factors, such as an alpha deletion, present.