Hello everyone, in this session I’m going to discuss TALASIS. It’s a very important topic from an exam point of view, so let’s start TALASIA. So in this session basically I’m going to discuss the TMIA under the following headings: first I will let you know the introduction, then I will let you know the classification. In the classification I will be discussing two types of THALIA, the BETA THALIA and the ALPHA THALIA.

Definitions, Pathogenesis, Types, Clinical Features, and Lab Diagnosis

I will be telling you the definition of both of them, the ULTR PATHOGENESIS, the exact mutation in both of them, the various types of both of them, three types in both of them, clinical features and the LAB DIAGNOSIS. Lab diagnosis I will be discussing basically of BETA THALIA which is important from exam point of view, so we will be discussing THALIA completely like this. Let’s start it.

Structure of Hemoglobin and Globin Chains

So basically there are four globin chain in all of them, all the hemoglobin have four heem and four globin. Currently I am not concerned with he because THALIA is a disorder of globin, you know it is a globin opathy. So there are four globin chains in all of them, you can see the formulas 2 Alpha 2 Beta in hemoglobin A, 2 Alpha and 2 GMA in hemoglobin F and two alpha and 2 Delta in hemoglobin A2. So four globin chains are there.

Types of Globin Chain Problems

Now there can be two problems with the globin: either the globin there is some problem in the structure of any of the globin chain, that is known as structural abnormality known as qualitative abnormality, the quality is not good, or else the quality is good but the amount is not normal, that is known as quantitative abnormality.

Qualitative vs Quantitative Abnormalities

So globin opathy there can be two problem in the globin chains: the qualitative, the quantitative. Qualitative means structure is not normal, there is some problem in the structure structural abnormality, and the quantitative the amount is less, the amount is not normal. So basically the two types of disorders, the hemoglobinopathies or specifically globin opathy are qualitative and quantitative.

Example of Qualitative Abnormality: CLE Cell Anemia

The qualitative one, the example is CLE cell anemia. In CLE cell anemia the beta chain there is a mutation in the beta chain Gene, so the beta chain which is formed is abnormal structure, so it’s a qualitative abnormality. But currently I’m teaching you talmas.

Quantitative Abnormality of Globin Chain

Coming on THALIA, so what is THALIA? What we have learned it is the quantitative abnormality of the globin chain, so be the globin chain are normal in structure but their synthesis is less and sometime it may be zero, sometime it is reduced, sometime it may be zero, right?

Types of TALISIA Based on Globin Chain Affected

So there are two type of globin chain in hemoglobin A. Now in hemoglobin A we have two alpha 2 Beta, so there are two type of TALISIA: if Alpha is less or absent it’s ALPHA THALIA and if beta is less or absent it is BETA THALIA.

Relative Abundance of Alpha and Beta Chains

Now you can see if Alpha is absent or reduced so beta will be, uh there it will be, you know the beta will be relatively more than Alpha, so it is known as Alpha thalis, or if the beta is less or reduced so Alpha will be relatively more, it is known as beta Thalia, right?

Approach to Teaching Beta THALIA

We will see the details of all of them one by one. Let’s start BETA THALIA in detail first. First I will teach you beta in detail, the types of the beta, the pathogenesis of the beta, then I will come on Alpha and teach you Alpha in detail. So let’s start with BETA THALIA.

Problem in Beta Chain in Beta THALIA

And BETA THALIA I told you the problem is with the beta chain of the globin, the beta chain is either less or total zero, that is known as beta thymia, so the beta chain imagine the beta is absent, either it is reduced or absent, right?

Formation of Hemoglobin A Requires Both Chains

So hemoglobin A cannot formed because for the formation of hemoglobin we require two alpha 2 Beta. Now Alpha is there but beta is not there, so how hemoglobin A will be formed? So hemoglobin A will not form, that is the problem with beta Thalia.

Types of Mutations in Beta Chain Gene

So the gene for beta chain is located on chromosome number 11. On chromosome number 11 there can be point mutations, there can be splicing mutation, there can be termination mutation, there can be promoter mutation, any of them, all of them are point mutation.

Hemoglobin F Formation in Beta THALIA Major

The hemoglobin F, what is hemoglobin F? Alpha 2 gamma 2. I’m saying beta is absent now. Alpha is normal but normally Alpha bind with Beta and it forms hemoglobin A, it forms hemoglobin A like this but I’m saying now Beta is absent, so with whom the alpha will bind?

Alpha will bind with gamma and because of which hemoglobin F will be formed, so hemoglobin A is absent or reduced and hemoglobin F normally less than 1%, no it will be more, it will be more, it can be as I as 98% here in major in beta Thalia major, right?

Mutation Status on Chromosome 11

So the two genes are there, both are mutated, so on chromosome number 11 we have a pair of chromosome number 11, on each chromosome we have one gene of the beta, one gene here, one gene here, so I’m telling you there is point mutation in them that is leading to Beta Thalia.

Severity and Blood Transfusion in Beta THALIA Major

It is severe anemia requiring very frequent BL blood transfusion since birth, so very frequent every week or twice a week or every 15 days blood transfusion is required depending on the percentage of hemoglobin A which can be synthesized, and lesser the percentage of hemoglobin A more frequent is the blood transfusion required.

Globin and Heme in Blood Transfusion

Now you cannot give only globin, along with globin you will give he also but patient do not require he, patient require only globin, patient is not requiring he but he alone you cannot give the globin.

Accumulation of Iron and Organ Damage

Now you will give complete hemoglobin in the RBC in blood transfusion, so the heem will accumulate in the form of the iron and such patient which require very frequently blood transfusion they have iron overload and that is the cause of the death.

Effects of Iron Overload on Organs

You know the iron overload will deposit in various organs, the heart, the pancreas, the kidney causing the failure of these organs and leading to the death, right?

Bone Marrow Expansion in Response to Anemia

And to compensate the bone marrow cavity, the medular cavity, you know the marrow cavity will expand, so that is the clinical features.

Types of Alpha THALIA Based on Gene Deletions

Now there are four types of Alpha Thalia: if one gene is deleted it is known as trait Alpha Thalia, trait.

If two are deleted it is known as carrier Alpha Thalia, carrier.

If three are deleted it is known as HbH disease and if all four are deleted it is known as hydrop fetalis.

Classification Summary of Alpha THALIA

So I hope you got it right, I hope you got it.

So that is the classification, so you can understand the classification.

You learn it’s deletion, it’s not point mutation.

Chromosomal Differences Between Alpha and Beta THALIA

So please understand the basics, the difference you can see now what I mean to say here: here is the point mutation, point mutation leading to Beta Thalia and here is the deletion, deletion of them leading to Alpha.

Basic Difference in Mutation Type Between Alpha and Beta THALIA

So four types, four types of Alpha Thalia, that is the basic, the basic is that point mutation on chromosome 11 the beta Gene leading to Beta Thalia and deletion on chromosome number 16 the alpha Gene leading to Alpha Thalia.

So beta Thalia is due to point mutation, Alpha Thalia is due to deletion.

Can I go ahead?

Clinical Types of Alpha THALIA

So that is a molecular pathogenesis.

The four types I already taught you, so if one of them is deleted, one gene is deleted it is known as Alpha Thalia carrier, it’s known as carrier and it’s asymptomatic.

If two of them are deleted, two of them are deleted, it’s known as trait, again mild anemia hardly any anemia, hardly any symptoms although asymptomatic no, but three and four are deleted it’s problematic.

If three is deleted it is known as hemoglobin H disease and if four is deleted is known as hemoglobin hydrop fetalis.

Effects of Multiple Alpha Gene Deletions

So let me tell you what will happen if three are deleted and four are deleted.

So if one is deleted carrier asymptomatic, two are deleted it’s trait again asymptomatic or mild, here it’s asymptomatic, here it’s mild anemia but three and four is problematic.

So let me show you three and four, if three are deleted what will happen, if four are deleted what will happen?

Hemoglobin H Formation in Three Gene Deletion

So if three are deleted the alpha is almost absent now, so beta will form the tetramer because Alpha is absent.

So what the beta will do? Beta will form normally two alpha 2 Beta but now Alpha is absent, three of them are deleted, right?

So Alpha is absent, so beta will form tetramer, it is known as hemoglobin H.

It is an abnormal hemoglobin known as hemoglobin HED.

Hemoglobin H have High affinity for oxygen, it will trap the oxygen and will not leave the oxygen leading to hemolytic anemias, it will be trapped in the screen, that is hemoglobin H, right?

Hemoglobin Bart Formation in Four Gene Deletion

And if Alpha is absent gamma is forming the tetramer, it is known as B hemoglobin.

So please understand here the tetramer is of beta, here the tetramer is of gamma because the alpha is absent.

Now please understand the alpha is absent so either the beta will form tetramer or the gamma will form tetramer.

If beta form tetramer it’s hemoglobin H and if gamma form tetramer it’s hemoglobin B.

Hemoglobin B here also the oxygen affinity is high and it will lead to intrauterine death, it is known as hydrop fetalis.

The fetus still birth or in utero death of the fetus, that is hydrop fetalis.

Severity of Alpha THALIA Types

So the two different here three genes are deleted and here all four are deleted.

The most severe is this one and second number severe is this one, you got it?

So hemoglobin H it is moderately severe anemia require occasional blood transfusion but hydrop fetalis most dangerous here, three genes are deleted and here all four genes are deleted, right?

It is the most dangerous form.

Here B hemoglobin is formed and here it leads to intrauterine death.

Summary of Alpha THALIA Hemoglobin Types

So in hemoglobin H disease hemoglobin H is formed, that is the tetramer of beta and in hemoglobin fetalis hemoglobin Bart is formed, hemoglobin Bart is formed, that is a tetramer of gamma, you got it?

Summary of Alpha THALIA Types and Hemoglobins

So Alpha Thalia let me summarize: there are four types of alpha Thalia.

What are the four types? Depending there are four genes of alpha, two on each chromosome number 16.

If one is deleted, if two is deleted, if three is deleted, or if all four are deleted.

The most severe form if one is deleted it is known as carrier, it’s asymptomatic, okay?

If two are deleted it’s known as trait, it’s mild anemia hardly require any transfusion.

If three are deleted it is known as hemoglobin H, the name of the disease is hemoglobin H in which hemoglobin H is formed and hemoglobin H is a tetramer of BETA and if four are deleted it is the most severe.

Here hemoglobin Bart is formed.

The hemoglobin Bart, the name of the disease is hydrop fetalis in which hemoglobin Bart is formed and it is a gamma tetramer.

So see the name of the disease, see the name of the hemoglobin.