In this lecture, we will discuss
sickle cell disease in children.
Let’s recall some basic science
about sickle cell disease.
This is an autosomal
There is a point mutation for
codon 6 on the beta-globin gene
on chromosome 11
at position 15.5.
This point mutation results in
a single change in amino acid
which makes the
hemoglobin less soluble.
We call a patient with the
sickle gene hemoglobin S or HbS
and a normal patient is HbA.
So a patient who is homozygotic for sickle
cell disease will typically be hemoglobin SS
and a normal patient will be hemoglobin
AA and the carrier will be hemoglobin AS.
Here is an example of
cells that are sickling
and you can see in the
sickled cells labeled SC
that these cells have
less soluble hemoglobin
resulting in that abnormal
shape of the cell.
These cells are more friable and they
don’t carry oxygen quite as well.
This is compared to the normal
cells which are nice and round.
So the rate at which
people have hemoglobin
sickle genes is different
depending on ethnicity.
And as you can see in the United States,
almost 7%, a little bit over
7%, of African Americans
carry a hemoglobin AS
or have sickle trait.
This is compared to, for example,
only 0.7% of Hispanic Americans.
It’s in 30% of patients
from Sub-Saharan Africa.
In India, it’s around 13%.
In the Middle East, there’s a wide
variability in terms of the rates,
depending on where you
In Greece, the rate is 1.5-7.5%
and the Caribbean is 4-10%.
What’s interesting about
these differences is that
the disease or carrying the sickle gene
seems to be somewhat protective of malaria.
So in populations that have evolved in
areas where there is a lot of malaria,
rates of sickle are higher.
So let’s talk a little
bit about hemoglobin C.
So hemoglobin C is another
mutation of the hemoglobin
and it’s about a quarter
as common as hemoglobin S.
In a patient who has one
S and one C mutation,
we call that
hemoglobin SC disease.
Hemoglobin SC is not as
severe as hemoglobin SS.
These patients have about
half as many pain crises
as the patients who are
homozygotic for hemoglobin SS.
They have a lower risk of chronic issues.
They have a longer life expectancy by
almost 20 years, about 65 versus 45.
And they have a higher incidence
however of retinopathy in particular.
This is because they
have a higher hematocrit
which causes part
of the problem.
Switching, there’s another variant
that we should think about
because thalassemia is also very
common in areas where there is malaria
and the patient may inherit a sickle
gene as well as a thalassemia gene.
We call this sickle-beta-thal.
A patient may be beta
zero or beta plus,
if there is some
hemoglobin A expressed.
So patients with beta zero
expressed, almost no hemoglobin A
and when they express
some, they are beta plus.
So, sickled beta zero has a similar
prognosis as hemoglobin SS disease
because they are not
making more hemoglobin A.
However, in patients
with sickled beta plus,
these patients have
a better prognosis.
They are making more hemoglobin A
and the hemoglobin is more soluble.
However, this is highly variable
and it’s variable in terms of the
course of illness depending on how much
of their hemoglobin
A is expressed.
Patients can also have
sickle alpha thalassemia.
This is a milder illness
than hemoglobin SS disease.
Another variant is patients
with hemoglobin SS disease
who have persistent fetal
This is very protective against
symptoms of sickle cell disease.
If a patient has a 10 or 20% persistence
of hemoglobin F expression,
they have a much better prognosis in
terms of their sickle cell disease.
There are lots of other
variations of sickle cell that
are beyond the scope
of this conversation,
but just be aware that there
are lots of variations
and that sickle and thalassemia and even
persistent fetal hemoglobin all interplay.