brief definition or summarisation of the term monogenic disorder is that it can
be defined as follows Mendelian or monogenic disorders are the type of genetic
disorders in humans that arise from a mutation in a single gene.
categories of illnesses usually may be spontaneous where it seemingly arrives
‘randomly’ are familial in nature and are autosomal or sex-linked, may also be
in two distinct groups as it can be dominant or recessive as well.
can be different ways to inherit these groups of disease it can be autosomal dominant,
autosomal recessive or x linked.
recessive inheritance is when two faulty genes are inherited typically in these
types of scenarios both of the parents would firstly carry the gene, resulting
in a secondary 25 % chance of a resulted disorder with each child.
of monogenic disorders:
disease was first described by Dr.James B.Herrick in 1910. The patient was a
black male that had symptoms of shortness of breath , palpitations and yellow
is an inherited disease which is diagnosed as an insufficient amount of healthy
red blood cells to transport oxygen around the body as red blood cells take
shape of a sickle allowing them to be easier to destroy.
is caused by defective haemoglobin which is the oxygen carrying protein in red
Sickle cell in the Haemoglobin A the beta globin chains end up misshapen due to
mutation in beta globin gene.
is an autosomal recessive disease that requires inheritance of two sickle cell genes
so it requires a mutation in both copies of beta globin genes. Having only one
copy of the mutation usually causes no health problems unless they are exposed
to extreme conditions for example high altitudes or dehydration
that consequence from sickle cell disease are the outcome of peculiarly shaped
sickled red blood cells that obstruct the stream of blood this abnormal
haemoglobin known as haemoglobin S.
unusually shaped sickle cells are disposed to rupture. Another consequence of
this disorder is that it can also cause an obstruction of blood vessels that
may cause severe viscera damage and pain.
degeneration of the usual biconcave shape of the red blood cells into the
sickled shaped shape can be stimulated by low oxygen levels , increased acidity
or low volume of blood.
patient who has sickle cell disease can become more susceptible to
infections as the impaired cells congest
disorder that affects the lungs , the word cystic fibrosis refers to the diseases affect on the pancreas where it
produces cysts and excess connective tissue.
is a autosomal recessive disorder associated with the CFTR gene (cystic
fibrosis transmembrane conductance regulator gene ) this codes for CFTR protein
causes by mutation in CFTR gene however since its autosomal recessive you must
inherit a faulty gene from each of the parents , if only one parents had the
disorder than the child is only a carrier.
common in people of European descent.
is a channel protein that pumps chloride ions into various secretion this helps
draw water into secretions causing it to become thinner the most common CFTR mutations is the Delta
F508 mutation which is where 508th
phenylalanine amino acid is deleted causing misfolding preventing its migration
causing a lack of CFTR on epithelial surface causing it to be unable to pump chlorine
now secretions are thick.
new-borns thick secretions can affect meconium making it sticky and cause it to
get stuck in the intestines which is a surgical emergency.
in early childhood pancreatic insufficiency is most common affect of CF as
thick secretions block pancreatic ducts preventing digestive enzymes from
making it to small intestines without these enzymes protein and fat are
unabsorbed and over time this will cause poor weight gain and failure to
thrive. Fat unabsorbtion will lead to steatorrhoea
or fat containing stools eventually leading to
pancreatic damage due to local inflammation leading to acute pancreatitis and
with repeat episodes may lead to chronic pancreatitis.
In Childhood lung problems crop up cilia usually keeps airway clean however
with thick mucus it is more difficult to clear, causing a build-up of bacterial
colonies causing symptoms such as cough or fever.
problematic bacteria are staphylococcus aurous (gram positive) and pseudomonas
aeruginosa (gram negative) both of which can be hard to treat if they are
resistant to antibiotics.
bacterial infection and inflammation can lead to bronchiectasis which is airway
wall damage causing permanent dilation of a bronchi coughing up of blood may
also be present.
time the repeated CF exacerbations may lead to respiratory failure which is
leading cause of death in patients with cystic fibrosis.
can also cause infertility in men as they lack the vas deferens. Men and women
may also have digital clubbing, nasal polyps which are tissue growths in the
nose and allergic bronchopulmonary aspergillosus which is a hypersensitive
reaction to aspergillus fumigatus which may live in sinus or lung cavity.
known as PKU is an inherited disorder of amino acid metabolism which can cause
mental retardation if not treated early. Both parents must carry the mutated
version of the PAH gene for the child to be affected.
is very rare 1 out of every 15,000 babies in the United States are born with
more common in those who have native American or northern European ancestry.
are immediately checked for PKU as soon as they are born and are treated using
a special diet.
is caused by the inability of some people to process the amino acid
phenylalanine however if this is not processed it builds up in the blood. This
causes nerve cells and brain damage.
respond normally in comparison to others during the first few months however if
the PKU is not treated they start losing interest very quickly in things when
they are 3 to 6 months old.
the time they are 1yr old they are not developing as they should.
PKU also makes child smell musty as they have a
build-up of phenylalanine in their breath , urine and sweat.
may also have dry skin , rashes or convulsions.
also suffer from microcephaly which is characterized as an unusually small
body processes phenylalanine into tyrosine which produces melanin which darkens
skin and eyes kids with PKU cannot process phenylalanine into tyrosine so they
have very light skin and blue eyes.
The treatment for patients affected with PKU
is a very specific diet they will usually show no symptoms if the diet is maintained.