In this lecture, we’re going to
discuss thalassemia in children.
So thalassemia is an inherited
It happens as a result of an
abnormality in hemoglobin synthesis
in either the alpha
or the beta subunit.
And mutations in the alpha or beta
subunit are usually autosomal recessive.
So patients can be carriers of disease.
Let’s remember some basic science
about the hemoglobin molecule.
Each hemoglobin molecule has
two alpha and two beta subunits.
But in the genome, there are two copies of
the beta gene, these are on chromosome 11
and four copies of the alpha gene,
these are found on chromosome 16.
So when the patient has an abnormal
mutation in one of these subunits,
it leads to an excess of
the unmutated subunit.
That buildup of
results in cells breaking open
prematurely and hemolysis.
So we tend to see alpha thalassemia
in areas where there is more malaria
or among people who historically
were more likely to get malaria,
because having alpha thalassemia,
much like having sickle cell trait,
was somewhat protective
of the disease.
The severity of alpha thalassemia
depends on how many of those
four alleles that are in
the genome are affected.
Let’s go through that.
If a patient has only
1 alpha affected,
they have dash and then a normal alpha
and then two other normal
alphas on the other gene,
this patient is found to have
alpha thalassemia minima.
These patients are essentially
silent gene carriers.
They don’t have any symptoms.
If on the other hand,
they have alpha/alpha
and on the other chromosome, two mutations,
this is alpha thalassemia minor.
This is more common in Asian
populations especially Southeast Asia
and these patients may have
a mild microcytic anemia
but are generally
Alternatively, they could have
1 mutation on each chromosome,
this is also alpha
but we see this variant more in Africans,
again, a mild microcytic anemia.
If they have 3 mutations, this
is called hemoglobin H disease.
These patients will have a
significant microcytic anemia
Alternatively, if they have
mutations in all four alpha genes,
this is alpha thalassemia major.
These patients will be edematous as a
newborn and often die before birth.
They may have hydrops fetalis.
So let’s look at beta thalassemia now.
Remember, beta thalassemia,
there is only two alleles,
but there are two types of mutations
that you can have to a beta subunit.
You can have beta plus where there is less
production of that protein from the gene
or you may have beta zero,
in which there is no production of
the protein at all from this gene.
So we now have different
variations of disease.
If you are beta plus/beta
or beta zero/beta,
this is called beta thalassemia minor.
This presents usually
as a microcytic anemia.
Alternatively, if you are beta
zero/beta plus or beta plus/beta plus,
this is beta thalassemia intermedia.
These patients have a microcytic anemia
and occasionally require transfusions.
More severely, if you have two beta
zero copies, this is really bad.
This is called beta thalassemia major.
These patients have severe anemia.
They usually have hepatosplenomegaly.
They have significant iron overload.
They have bony deformities and generally,
there is death by the age of 20.
We’ll go through that
disease in more detail.
So let’s look at the basic
of beta thalassemia.
In beta thalassemia, because
they have mutated betas,
they have an accrual of
insoluble alpha globin.
That alpha globin forms inside that cell
and that causes an abnormality
in the erythroblast,
so that there is
and the bones are incapable of
making adequate red blood cells.
And most of those erythroblasts
will die inside the bone marrow.
Among those that escape,
there will be increased extravascular
hemolysis specifically in the spleen.
And these cells will collect there
and patients may get splenomegaly.
So let’s look a little bit deeper, however.
In patients where there is
and most of those erythroblasts
are dying in the spleen,
the patient is still getting a
normal amount of dietary iron.
They will have increased iron absorption
and they may develop iron overload.
These patients will also have extravascular
hemolysis which will result in anemia.
Remember, because these
patients are having anemia,
they may require
and blood transfusions
obviously also contain iron,
further contributing to the
systemic iron overload.
Furthermore, the tissue
hypoxia results in an
upregulation of erythropoietin
release from the kidney
and EPO that’s released will encourage
not only bone marrow expression,
but it will encourage that bone
marrow expression in such a way
that there will sometimes
be skeletal deformities
as a result of that marrow constantly being
encouraged to undergo erythropoiesis.
This can lead to a rather
Specifically, patients may develop
bone marrow that is so aggressive
that you can see these deformities not only
grossly when you approach the patient,
but on x-ray.
This is a classic skull
x-ray of an infant
with beta thalassemia
major, beta zero/beta zero.
You can see this picture has something
called a hair-on-end appearance
and that skull is
Additionally, this can
result in abnormal facies
and you can see a small appearing
nose, very prominent maxillae
as the areas of that skull that are requiring
to do hematopoiesis have expanded.
So the diagnosis of thalassemia is basically
made by hemoglobin electrophoresis
and that’s how we can decide what
type of thalassemia that patient has.
The treatment is fairly simple.
For patients with alpha
thal minima and minor
and for patients with beta thal
minor, we typically give folate.
This is because they have dietary increase
need for folate because of hematopoiesis.
For patient with more severe disease
such as hemoglobin H disease
or beta thalassemia intermedia,
we will not only do folate but patients
will require periodic transfusions.
If a patient has yet more severe disease
such as beta thalassemia major,
these patients may require transfusions
as much as every 2-3 weeks.
As a result, they require deferoxamine
to chelate the excess iron,
so it doesn’t buildup
in their tissues.
In severe cases, we may move
on to bone marrow transplant.
In alpha thalassemia major,
these patients are very sick.
They require in utero transfusions and
eventually a bone marrow transplant.
So that’s my review of
thalassemias in children.
Thanks for your attention.