Beta Thalassemia; Causes and Types (minor, major and intermedia). - YouTube

All right welcome back, so we have been talking about anemia,

microcytic anemia, now we're talking about

Thalassemia...in the last video we have talked about alpha-thalassemia (link in description). Today. We'll talk about beta thalassemia

So, Beta Thalassemia is a microcytic anemia, and again symptoms of anemia

Tired and pale, pale and tired...sometimes, I have murmur (flow murmer), sometimes I can get angina.

also...

exercise intolerance,

fatigue,

Etc. Beta thalassemia is very common in Italy so keep that in mind, okay?

So, as you know...

Hemoglobin has two alpha subunits, and two beta subunits...good

They are called

tetramers

excellent

Thalassemia by definition is a defect in globin

chain

synthesis

good, so this will lead to

two things; here you have the globin so

Decreased globin synthesis will lead to decreased hemoglobin

i.e. anemia

Good...what else?

when globin chain

Synthesis unbalanced hemo tetramers form so for example when alpha is not

present beta will form tetramers

They are insoluble

They will precipitate in RBC's. The spleen macrophages will recognize that and will cause hemolysis

Will destroy these abnormal RBCs.

this will lead to...

ineffective

erythropoiesis

Why? -Bone marrow tries to respond to the hemolysis by producing more...

red blood cells. However,

Globin synthesis decreas; I cannot synthesize

Good RBC's, or sufficient RBC's. It's called ineffective

erythropoiesis

beta thalassemia

The problem is in chromosome 11

Do you remember what chromosome was involved in alpha-thalassemia?

Correct! - 16 ...Okay, how to remember beta and 1? -just draw beta like this:

And then draw an 11 like this.

Okay, so we can do it better. This is the 11 and then this is the beta, like this.

Just any way to remember, okay, it's common in the Mediterranean, Middle Eastern and

Asian population...Please, remember Greece and Italy.

Greece and Italy beta thalassemia

chromosome 11

Beta thalassemia can be mild or severe

Mild anemia usually due to a splicing defect

Go back to your

Molecular Biology and review this topic.

Severe anemia is due to a specific type of point mutation, called: nonsense mutation

There is a stop codon. Okay? That's introduced...

Earlier than usual. Stop codons are these as you know this will lead to termination...

Of protein synthesis, and in this case the protein is

the beta

globin

-in = protein

So, genetically speaking beta thalassemia can be either

heterozygous or

Homozygous

Heterozygous is beta thalassemia minor

homozygous can be either:

thalassemia intermediate or beta thalassemia major

chromosome 11

so, number one beta thalassemia minor

there is

Increase in the number of microcytic RBCs, of course.

Thalassemia is a microcytic anemia. However, in thalassemia

There is increased number of RBC's. Nobody know why!!!

That's interesting so when you have microcytic anemia low hemoglobin, low hematocrit,

but, (and that's a big but)

RBC count is a little bit high

Iron studies are normal, please suspect thalassemia.

Beta thalassemia minor; it's minor, so it's either asymptomatic or there is minor anemia

So what will happen to the normal adult hemoglobin A? - it will slightly decrease

Hemoglobin A2 will increase, hemoglobin F will slightly increase.

so,

Hemoglobin electrophoresis will show this. Hemoglobin electrophoresis in beta thalassemia minor is...

abnormal

Contrast that with the minor form of alpha-thalassemia, called:

the Alpha thalassemia trait

Trait you remember? Trait, where the hemoglobin electrophoresis was completely normal!

Alrighty, now the big one; Beta thalassemia major (also known as Cooley's anemia)

so, we start here by a problem in the

Beta globin production... Zero; there is none whatsoever; no beta globin production.

So what else do we have other than the beta? -Alpha... Alpha globin will form and precipitate forming...

Homo-tetramers, and these homotetramers will lead to two things:

first in the bone marrow...

the RBC's containing the Homotetramers will die...

Earlier before being released... why? - they are not healthy, they cannot survive.

So, they die... This is called ineffective

Erythropoiesis, as you know. What else will happen to these...

homotetramers? - they will precipitate in RBCs, so the

Macrophage in the spleen will recognize these

Oh, these are ill, abnormal RBCs, let's kill them!!! :O

So, they destroy the RBC', which leads to hemolytic anemia.

Hemolytic anemia? - the kidney will respond by increasing

Erythropoietin production

erythropoietin will lead to something called...

Erythroid hyperplasia

Erythroid is the cell line that produces RBC's and...

hyperplasia means increasing the number of cells, so we increased number of RBC's and...

We increase the formation, increased production in the bone marrow...

This is called: medullary

erythropoiesis

Fine. But, I need more, I need more factories to produce more RBC's, so

the spleen and the liver , or the

reticulo-endothelial organs

will take over. It's called extra-medullary

Hematopoiesis. They will start forming new

RBCs

Ok, they are working really hard. They will enlarge...

"hepatosplenomegaly"

Fine, the medullary cavity

inn the skull, and in the bones will enlarge. When they enlarge,

This will include the skull who give us an appearance on x-ray called hair on end appearance or

crew-cut

skull Crew-cut-hair skull

Also, the maxilla: the maxillary bone will enlarge leading to something called chipmunk facies

fine!

So, hemolytic anemia...so we need to give the patient blood.

Giving them blood? -we will make them

dependent on the

transfusion or transfusion-dependent

This blood contains iron, which will lead to iron overload...

Hemosiderosis and

secondary

hemochromatosis...What else?

anemia; hemolytic anemia is destruction of the

Hemoglobin, and hemoglobin has heme and globin.

Haeme has iron and protoporphyrin. Protoporphyrin will convert to unconjugated bilirubin, goes to the liver to be

Conjugated into the conjugated bilirubin

Okay, so this increase in unconjugated bilirubin

Will lead to unconjugated

hyperbilirubinemia

and of course

jaundice!

That's it for beta thalassemia major...if you understand this slide, you will know a lot of

information for your exam :)

Now, the last one: Beta thalassemia intermedia

It's an intermediate form it's not as severe as major, but it's also more severe than the minor beta thalassemia

So there is an a

Co-inheritance with alpha thalassemia trait. so, when you have beta thalassemia intermedia, usually you have also

alpha-thalassemia

trait

fine!

Okay, so there is also minor

Qualitative defect in the beta globin, so usually we have alpha and beta

Remember in beta thalassemia major, we don't have any beta. So, the Alpha

Increased forming Homotetramers. However in this condition. I have also alpha-thalassemia trait I have

Deficiency in this alpha globin chains, so I cannot increase them as much I cannot

Produce as much homotetramers, so there is less homotetramers

Than beta thalassemia major...There is less

Hemolysis, and of course, hemoglobin F Will increase since you don't have beta.

What will happen? -Gamma change will form when you have alpha and gamma. This is called

Hemoglobin F, the fetal hemoglobin.

Okay, that's it for thalassemia, guys

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