Definition:

Cystic fibrosis is an autosomal recessive disease that causes the body to produce a thick, sticky type of mucus, which affects various organs, including the lungs and the digestive system.

Epidemiology:

Cystic fibrosis affects around 100.000 people in the world and is one of the most common genetic diseases in Caucasian people. It usually emerges in early childhood. There are many different versions of this disease.

Aetiology:

This is an autosomal recessive disease, which means that it can also be carried by someone who is not affected by it directly but could pass it on to their offspring. It is caused by a gene’s recessive allele on the 7th chromosome that encodes a protein called CFTR.

Pathogenesis:

This protein’s function is to regulate the passage of chloride ions across cell membranes. Because of its malfunction, the normal passage of water from the inside to the outside of the cell is compromised, leading to the creation of mucus that is too thick and sticky. The mucus then ends up blocking glandular ducts and tubules of several organs, such as the lungs and pancreas.

Clinical picture:

The main symptoms regarding the respiratory system are:
recurring lung infections, caused by bacteria that can easily proliferate in the secretions in the lungs;
Inflammation of the airways
Persistent cough and eventual coughing up blood.
But there are also many symptoms regarding the digestive system, such as severe intestinal obstruction in the first days of life.

Therapy:

Since there are several different versions of this disease, there isn’t just one type of cure, but every patient has to be followed individually. Usually, these infections are kept at bay using various types of medication, and in severe cases, a lung transplant may be necessary.

This is a progressive, fatal neurodegenerative disorder, more specifically, the most common form of MND (motor neurone disorder), since 80-90% of MND patients are affected by ALS. The disease typically begins to manifest in people between 50 and 70 years old and is slightly more common in men. Some of the most common symptoms consist mainly of motor symptoms, however in many patients there have been found cognitive or behavioural changes aswell, but it is a spectrum disorder with FTD (frontotemporal dementia) being the most severe form.

Aetiology:

It is considered a sporadic disease (which means that it appears irregularly and in an unpredictable way) and even if it is considered familial (which means that it’s present in members of the same family but it doesn’t actually follow the Mendelian laws, they just have a shared genetic component among family members) studies suggest that heritability may account for up to 50%.

Pathophysiology:

ALS provokes a degeneration of both the upper motor neurones (UMN) and the lower motor neurones (LMN).
The first one can cause spasticity, brisk reflexes, and pathological UMN signs (for example: Hoffmann’s sign, Babinski response , jaw jerk, and more).
On the other hand, the LMN degeneration leads to anterior horn cell loss in the spinal cord, resulting in muscle wasting, fasciculations, and flaccid weakness.
While ALS can be attributed to many factors, some of the most important ones are protein misfolding and aggregation; in fact, the abnormal accumulation of TDP-43 and SOD1 proteins has been observed in affected neurons.
Another important factor is altered RNA signalling, which, when combined with oxidative stress and mitochondrial malfunction, causes problems in the cell's energy metabolism. This leads, among other things, to neuroinflammation that may be beneficial initially but becomes harmful over time. The end result is that axonal transport, cellular communication, and the regenerative abilities of the cell get progressively worse.
These mechanisms combined result in progressive motor neurone degeneration and the combination of UMN and LMN features.
Risk Factors:
ALS is probably a result of both genetic susceptibility and the environment in which one was raised and lived.
Over 40 ALS-associated genes have been identified; in particular, genes such as C9orf72 and SOD1 are more likely to cause the disease, but they aren’t the only factors.
As a matter of fact the risk of contracting the disease increases with age with its peak from 50 to 70 years and males are slightly more likely to fall sick (with a ratio of 1.5:1). Environmental triggers such as military service, exposure to: pesticides, solvents, heavy metals, and cyanotoxins; smoking and possibly elite athleticism (the researches are still going) play a big part in the increase of risk.

Definition:

Sickle cell anemia is an autosomal recessive disorder that causes red blood cells to take on a sickle shape and become less efficient, leading in some cases to severe symptoms such as serious anemia or even heart complications.

Epidemiology:

Sickle cell anemia is one of the most common autosomal recessive diseases, affecting around 300 000 babies born with the disease each year. It is mainly found in the Mediterranean area, the Middle East, Sub-Saharan Africa, and India. This is because the people who are healthy carriers of this disease are protected against malaria, a very common disease in places such as Sub-Saharan Africa and India.

Aetiology:

This is an autosomal recessive disease, which means that it can also be carried by someone who is not affected by it directly but could pass it on to their offspring. Sickle cell anemia is caused by a gene mutation on the 11th chromosome , which controls the production of a protein: hemoglobin.

Pathogenesis:

This mutation causes the hemoglobin (which is normally indicated as HbA) to have a single amino acid substitution (and is indicated as HbS). People who have both copies of mutated alleles (HbS HbS), so they are homozygotes, have red blood cells shaped as a sickle or as a half-moon instead of a biconcave disc, because when hemoglobin S releases oxygen, it tends to polymerize (aggregate) and form long fibers inside red blood cells. These fibers make the cells rigid and cause them to take on a sickle shape. This leads to red blood cells being less efficient and blocking blood vessels. While people who are heterozygotes (HbA HbS) are healthy carriers of the disease.

Clinical picture:

Homozygous individuals can have some light symptoms when the oxygen level is low, and they are less likely to contract malaria. On the other hand, people who are recessive homozygotes present symptoms that range from severe anemia to organ damage and heart problems.

Therapy:

In case of severe anemia, it is important to have blood transfusions or a treatment with hydroxyurea. The only known way to cure sickle cell anemia at the moment is a bone marrow transplant using stem cells from a compatible donor. These cells then replace the defective ones. Unfortunately, this cure can’t be used often because of the small number of compatible donors and the numerous side effects it can have.
Some experimental studies suggest that gene therapy may improve patients’ quality of life and reduce the need for transfusions, but long-term studies are needed to confirm these results.