Let’s go on to beta thalassemia.
So if alpha thalassemia you felt as
though was a little complicated,
It was, because you’re dealing with 4.
Heck of a lot easier.
Because in beta, you only
have two alleles total, okay?
Whereas in alpha, you have two
alleles from each parent.
Here, you have one allele from one parent,
another allele from another parent.
If I were you, I would know
chromosome 11, that’s important.
Now, I’m going to give you
a few scenarios in which
the boards really like because
they want to test your knowledge
in concept of beta thalassemias.
You will see what I’m referring to.
So that means that there’s
really only two patterns.
You miss one, that’s minor or
you miss two, that’s major.
But clinically, you need to be
able to identify the nomenclature,
so I’ll walk you through
There's your normal gene,
chromosome 11 shall
we say for beta.
If there is a mutation, maybe
it’s a splicing defect.
What does that mean?
Do you see the bottom picture where you
see the mutant type of splicing mutation?
Remember, you have introns and extrons
and normally should remove your introns.
Remember that from genetics.
Well what happens in splicing is
the fact that intron remains.
Do you see that white area, that
bar, the white bar that's empty?
That’s the splicing defect.
So you are not able to
have proper splicing.
And beta thalassemia primarily caused by
splicing mutations in beta globin genes.
So you want to keep that in mind.
This is just a graphic illustration of a
splicing mutation in beta thalassemia.
How many alleles total please?
Two, one from mother and one from father.
You have minor or major,
minor and major, that’s it.
None of this trait and
none of this HbH and such.
Now, the nomenclature does
become important here.
I need you to pay attention.
If you find a beta as what you see here,
if you find a beta with no superscript,
hematologically or clinically that
means a perfectly normal beta,
beta, beta gene, okay?
Or beta allele.
However, as soon as you see a superscript,
let me lay down the law for you,
if you find a superscript that means
there’s a mutation of some type.
Is that clear?
So be very careful because this
looks like it’s beta plus.
And if you didn’t know any better and you
didn’t speak this language of hematology,
you’ll think, “Oh! There
is presence of beta.”
No, no, no.
In order for you to have
a normal beta allele,
this means there should
be no superscript.
But the fact that
you find beta plus,
means there’s mutation and expression
here is going to be variable.
Meaning to say variably decreased.
So it won’t be normal,
it will be subnormal.
But if it’s beta not,
meaning beta zero as you see here,
no beta allele was present at all.
Now for simplicity purposes,
on your board exam,
let me tell you, if there’s
one beta with no superscript,
that’s from mother.
And let’s say from the
father, you picked up a beta
with either the superscript plus
or a superscript of the zero,
by the definition as far as your
concerned with your medical education,
that is beta thalassemia minor.
I don’t care nor should you
with that second beta that has been
mutated if it’s a plus or a zero.
But because you have one beta that is
perfectly normal, that is minor.
As I told you, this will be the only
part where it becomes a little tricky.
But if you understand the nomenclature,
then you will be in good shape.
What if you had both betas that
has some kind of superscript?
As far as your concerned,
that means it’s major.
In other words, that’s your Cooley.
Hopefully, they'll just give
you beta zero, beta zero.
It’s major, you’re done.
Or they will give you beta
and beta zero, that’s minor.
But if not by chance, at least you
know how to now interpret it.
Speaking of which, let’s go through.
I’m going to first give
you the most common
and then I will talk about the
one that rarely shows up.
So let’s talk about beta
You will notice the following,
exactly what I was referring to.
So now that we discussed it,
let’s take a look at it, so that
permanently stays in your head.
First, take a look at the
beta with no superscript.
Perfectly normal betas.
Next, you see the betas
with superscript 0/not
and beta plus superscript.
Either/or for you,
at this juncture of
your medical education,
that to you should mean
beta thalassemia minor.
Asymptomatic with mild anemia.
I’m going to skip over
intermediate for a second,
and then I’m going to
give you this one.
You definitely want to know this
and I’ll tell you why, why, why.
There are 2 betas,
both have superscript.
What does that mean?
Major, that’s it.
"But Dr. Raj, beta plus
means variable expression."
I don’t care neither should you.
This is beta thalassemia major.
What does that mean?
Severe anemia, severe anemia.
Now the only time, if you want
to take a look at the middle,
there is a bunch of variations.
The one on the middle is
called thalassemia intermedia.
It exist, but I’m just going to
mention it and know that it exist.
But your focus should be minor and major.
I will definitely walk you through on what
it means to be transfusion dependent.
I have to, I have to.
But before we move on now,
I need you with me right now to
predict what’s going to come next.
You tell me what beta globin is.
Which hemoglobin or
hemoglobins contain beta?
There’s a new one hemoglobin
that contains beta.
Whereas an alpha, all relevant
hemoglobins have alpha:
Hemoglobin A, A2, F, okay?
Here however, beta globin is
only which one, A’s and B’s?
Let me review real quick --
If you’re missing three alpha alleles,
you can’t produce any
You have to literally
produce some other globin.
Versus here, if you have
beta thalassemia major,
let’s stick to that, where you do
not produce much hemoglobin A.
May I ask you?
Could you produce hemoglobin A2?
Let’s see, that’s made
up of alpha and delta.
Oh, yeah, I can.
And what about hemoglobin F?
Oh, that’s alpha and gam--
Oh, yeah, I can too!
So those are going
So you end up producing more
hemoglobin F and hemoglobin what?
But what happened
to hemoglobin A?
Oh, that diminished.
I’m going to show you all this.
We’re just going to talk about
this and then we’ll look at it.
Always do this, every
you think about what you’re going to answer
then you take a look at the answer choices.
Don’t do it the other way around.
If you take a look at the answer
choices first, you’ll get confused.
I can guarantee that.
Efficiently, you look at the vignette,
you read through the clinical situation
and each line either rule in or you rule
out that’s relevant for your patient.
You’re literally the doctor,
the clinician, a detective.
You’ll predict what’s
going to happen.
If it’s there, fantastic.
Do you know how much time you spent?
Like you literally spent not
much time in an efficient way.
You need to train yourself,
it’s a marathon.
The boards are not --
It’s not a sprint.
You can't cram from this.
There is no way, no way.
So now my point is this,
97% is your normal hemoglobin A and
what happens in beta thalassemias?
That 97% will diminish as we shall
see on hemoglobin electrophoresis.
Okay, pathogenesis, what
does this mean to you?
Well, you tell me.
You’re going to have a
decrease in hemoglobin.
Tell me about your patient.
Symptomatic, kind of behaves like your?
Well, there's fatigue
especially upon exertion.
What else may happen?
You have decreased hematocrit.
What about your iron studies?
Yeah, leave it alone.
Okay, iron studies here
only dealing with globins.
So very similar in terms of alpha.