A 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.These 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.
There can be different ways to inherit these groups of disease it can be autosomal dominant, autosomal recessive or x linked.Autosomal 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.Examples of monogenic disorders:1)Sickle Cell Disease:This 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 eyes.This 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.
It is caused by defective haemoglobin which is the oxygen carrying protein in red blood cells.In Sickle cell in the Haemoglobin A the beta globin chains end up misshapen due to mutation in beta globin gene. It 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 Symptoms 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.
These 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.The 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.
The patient who has sickle cell disease can become more susceptible to infections as the impaired cells congest the spleen.Cystic Fibrosis:Genetic 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.It 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.Most common in people of European descent.CFTR 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.
In new-borns thick secretions can affect meconium making it sticky and cause it to get stuck in the intestines which is a surgical emergency.While 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.Later 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.Some 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.Chronic 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.
Over time the repeated CF exacerbations may lead to respiratory failure which is leading cause of death in patients with cystic fibrosis.It 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. 3)PhenylketonuriaAlso 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.PKU is very rare 1 out of every 15,000 babies in the United States are born with it.Is more common in those who have native American or northern European ancestry.
Babies are immediately checked for PKU as soon as they are born and are treated using a special diet.Phenylketonuria 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.
Symptoms of PKU:Babies 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.By the time they are 1yr old they are not developing as they should.Untreated PKU also makes child smell musty as they have a build-up of phenylalanine in their breath , urine and sweat.They may also have dry skin , rashes or convulsions. They also suffer from microcephaly which is characterized as an unusually small head.
