Introduction children, it is very common in some

Introduction

The topic of focus in this essay is sickle cell
disease, which is a genetically inherited disorder that affects the blood. In
this essay the aim is to provide a
description of sickle cell disease in relation to how it is inherited and how
it affects a person’s health. The essay will follow an order as follows; firstly,
the pattern of inheritance will be defined, then the biology of the disease
will be explored and lastly the techniques
by which the disease is diagnosed will be described.

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Pattern
of Inheritance

Sickle cell disease occurs because of a mutation in
the beta-globin gene (HBB gene) which is located on chromosome 11. It is an
autosomal recessive disease, which means that two copies of the mutated gene,
one from each parent, are required for the disease to manifest. If a mother and
father are both heterozygous carriers of the mutated gene their children have a
25% chance of being affected by the disease and 50% of their children are likely
to be carriers. Autosomal recessive diseases characteristically tend to skip
generations and males and females are equally affected.

Interestingly, although sickle cell disease is life
threatening and affects children, it is very common in some parts of the world
seemingly due to its correlation with malaria. People who have sickle cell
trait, that is those who are heterozygous for the sickle cell allele, seem to
have a level of protection against malaria, meaning sickle cell carriers have
an evolutionary selective advantage in countries where malaria occurrence is
high, for example Africa. This unfortunately has the result that the mutated
gene is carried on through the generations.

Biology of the Disease

Cause

The cause of sickle cell disease is defective
haemoglobin. For context, haemoglobin is the molecule needed to carry oxygen in
red blood cells. It is a protein comprised of four peptide chains which are
bound to a haem group. Although there are many combinations of these chains, it
is predominantly Haemoglobin A (HbA) which is found in adult blood and consists
of two alpha-globin chains and two beta-globin chains. In people with sickle
cell disease there was found to be a single nucleotide non-conservative missense
mutation in the beta-globin gene. This mutation causes the sixth amino acid of
beta-globin which is normally the hydrophilic glutamic acid to be replaced with
hydrophobic valine. A haemoglobin molecule with two alpha-globin chains and two
mutated beta-globin chains is referred to as sickle haemoglobin (HbS). It is
interesting to note that sickle cell disease was the first monogenic disease
identified and it became a model for subsequent diseases which could be traced
to a point mutation in a specific gene.

Effect

As a consequence of valine being hydrophobic, HbS
changes shape when deoxygenated. It is this change in shape which allows many
HbS molecules to bond together and form polymers, which causes red blood cells
to be altered into a crescent or sickle shape. The factors that encourage red
blood cells to sickle are hypoxia, acidosis and dehydration which can all be
improved with the oxygen and fluids as fundamental treatments. Sickle cell
carriers, despite not having the disease, can experience symptoms when subject
to extreme dehydration or high altitudes. The sickling of red bloods cells in
homozygous individuals causes serious health problems due to two main factors;
weakening of the cell membrane and vaso-occlusion.

Anaemia is the direct result of the weakened cell
membrane as intravascular haemolysis which is premature destruction of sickled
red blood cells occurs. As red blood cells disintegrate, free haemoglobin is
released into the blood plasma and is bound by haptoglobin, so low haptoglobin
levels are an indicator of haemolysis. In addition, haem groups are recycled
and result in the production of unconjugated bilirubin, an excess of which
causes conditions such as sclera icterus, jaundice and gallstones. In response
to anaemia, the bone marrow produces an increased amount of reticulocytes
(immature RBCs) which leads to new bone formation leading to expansion of
medullary cavities in skull leading to enlarged cheeks. Anaemia can also cause
extramedullary hematopoiesis (RBC production outside the bone marrow) often in
the liver causing hepatomegaly (enlarged liver).

Vaso-occlusion tends to occur in the capillaries due
to the shape of sickled red blood cells and can have devastating effects. Dactylitis
is observed in children with sickle cell disease, which is painful swelling of
the digits due to clogging of blood flow in hands and feet. As the patients
life progresses other bones are affected causing sickle cell pain crises and
avascular necrosis. Red blood cells can also clog up the spleen which can lead
to an infarct to the spleen as well as an enormous backup of blood in the
spleen (splenic sequestration) which can be life to threatening. Over time
splenic infarcts can scar the spleen so much that it results in an
auto-splenectomy. Without a functional spleen a person is vulnerable to bacterial
infections such as pneumonia, influenza, meningitis and salmonella. Sickle red
blood cells can also form blockages in the cerebral vasculature causing strokes
and Moya-Moya disease. Sickle red blood cells can get stuck in the blood
vessels of the lungs leading to acute chest syndrome. In the kidneys, clogging
can cause necrosis which causes blood and protteins to enter the urine. Another
problem that men experience is priapism, a painful prolonged erection due to
blockage of capillaries in the penis.

Diagnosis

Sickle cell disease can be diagnosed by looking for
sickle cells in blood smears or by identifying HbS using protein electrophoresis.
It is important to diagnose this disease as early as possible as early
treatment can prevent many complications and in some countries, it is included
in the new-born blood spot screen test.

Conclusion

In summary, sickle cell disease is a hereditary
condition with an autosomal recessive pattern of inheritance. It is caused by a
mutation in the beta-haemoglobin gene resulting in misshapen haemoglobin
molecules, which in turn deforms red blood cells into a sickled shape. The sickled
red blood cells cause problems for two main reasons; they are easily destroyed
causing anaemia and related complications, and they cause vaso-occlusion in
many parts of the body producing painful symptoms and eventual fatality.