Autosomal Recessive Inheritance: Principles, Patterns, & Associated Disorders

In humans, there are 46 chromosomes found in each cell inside their body and they are arranged in 23 pairs. The first 22 pairs are called as autosomes whereas the last pair is called the sex chromosomes (XX for females and XY for males). Basically, one chromosome in each pairs is inherited from each of the individual’s parent.

• For instance, the term “autosomal^[1]” refers to any gene located on the first 22 pairs of chromosomes (autosomes). Meanwhile, “recessive” indicates the condition that manifests only when both copies of the same gene are present, because usually, the “dominant” form of the gene is able to mask its expression.
• When combined, autosomal recessive^[2] refers to a genetic condition that manifests only in individuals who have received two copies of a gene found in the autosomes, with one gene being masked of expression.

It is quite unusual to observe any history of autosomal recessive within families because a carrier of the condition should have a child with someone who also bears the same condition. The probability of the manifestation of the condition is very low that even if both the parents have the gene for the condition (there is only a 50% possibility that the child will be a carrier of the condition), there is only a 25% possibility of passing down the recessive gene to the child and manifesting it.

• This probability is the same for every pregnancy, regardless of the number of children the parents have. In addition, there is a so-called horizontal transmission wherein siblings born in the same generation are affected.
• Most of the time, the heritable condition has an early onset with a more severe phenotype.
• Furthermore, since the gene is located in the autosomes, males and females have the same chances of being affected.
• The diagram below will help explain the possibilities of acquiring the gene from the parents.

  

The concept of a compound heterozygote^[3] is very crucial to the understanding of autosomal recessive inheritance. This concept refers to the fact than an affected individual bear two alternative forms of a single gene (referred to as an allele). This is very different from the concept of homozygous mutations where both forms of a particular gene exhibit identical forms of the mutation.

Further information regarding autosomal recessive inheritance can be obtained from this video link:

Also known as PKU, phenylketonuria^[4] is a hereditary disorder that increases the amounts of phenylalanine in the blood. While phenylalanine is an essential amino acid necessary for the biosynthesis of other amino acids, too much of it can become detrimental to the body.

• Generally, PKU causes intellectual disabilities, low birth weight, heart defects, and microcephaly (abnormally sized head).
• The signs and symptoms of the disorder can range from mild to severe. The most severe case is known as classic PKU and affects infants. When left untreated, these individuals may have a mouse-like odor, being a side effect of high levels of phenylalanine in the body. They also tend to have lighter skin color and skin disorders like eczema.

Sickle cell disease^[5] is a group of hereditary red blood cell disorders. In particular, they affect hemoglobin which is the molecule that delivers oxygen to the cells in the body. Normally, hemoglobin are disc shaped and this structure gives the cells flexibility to move around the blood vessels.

• However, affected individuals have the molecules known as hemoglobin S which are distorted hemoglobin that are crescent shaped or “sickle” shaped.
• Because of their shape, they are no longer flexible and tend to stick to the walls of the blood vessels, hence causing blockage that impede blood flow. As a result, oxygen cannot be delivered to other cells and tissues.
• This type of disease is characterized by hemolytic anemia, vascular obstruction and dysfunction, stroke, and hand-foot syndrome.
• The most common and most severe form of sickle cell disease is the sickle cell anemia.

Canavan disease^[6] is a fatal and progressive neurological disease that starts during infancy. It caused by an inherited gene mutation that causes the lack of enzyme that results to the degeneration of the white matter in the brain. As a result, the transmission of nerve signals and impulses is disrupted.

• The signs and symptoms of this disease is variable but it is generally characterized by an increase in the size of the head, lack of control for it, low visual responsiveness, and abnormal stiffness of the muscles.
• Affected individuals have trouble in movements like crawling, walking, or even talking. Through time, they may even be paralyzed.
• This disease is very prevalent in people of the Ashkenazi descent Jewish ancestry.

Gaucher disease^[7] is a type of heritable genetic disorder that is caused by the mutations in the glucocerebrosidase (GBA) gene, causing the inadequate breakdown of the lipid called glucocerebroside.

• Affected individuals have the trouble of breaking the lipid due to the low levels of glucocerebrosidase. This results to the build up of the lipid in various organs like the liver, bone marrow, spleen, and others.
• Symptoms include the enlargement of both liver and spleen, bone diseases, and low levels of red blood cells and platelets.

Cystic fibrosis is a condition that /is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Mutations in the said gene tend to affect the chloride channels on the epithelium of the lungs, pancreas, and other organs.

• Such will lead to the disruption of the movement of chloride and sodium ions, and water molecules into and out of the cells, causing the abnormal production of mucus. This mucus will block the airways and other glands which will further lead to end-stage lung disease.
• This disease may also cause abnormalities like malabsorption, salt-loss syndromes, and in males, obstructive azoospermia.
• The severity of the disease is dependent on the severity of the mutations in the gene, and the environment.