Autosomal Recessive: Cystic Fibrosis, Sickle Cell Anemia, Tay-Sachs Disease

Genes are inherited from our biological parents in specific ways. One of the basic patterns of inheritance of our genes is called autosomal recessive inheritance.

What is autosomal recessive inheritance?

Autosomal recessive inheritance means that the gene is located on one of the autosomes (chromosome pairs 1 through 22). This means that males and females are equally affected. "Recessive" means that two copies of the gene are necessary to have the trait, one inherited from the mother, and one from the father. A person who has only one recessive gene is said to be a "carrier" for the trait or disease, but they do not have any health problems from "carrying" one copy of the gene. Most people do not know they carry a recessive gene for a disease until they have a child with the disease. Once parents have had a child with a recessive trait or disease, there is a one out of four, or 25 percent chance, with each subsequent pregnancy, for another child to be born with the same trait or disorder. This means that there is a three out of four, or 75 percent chance, for another child to not have the trait or disease.

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The birth of a child with a recessive condition is often a total surprise to a family, since in most cases, there is no previous family history of a recessive condition. Many autosomal recessive conditions occur this way. As mentioned above, a person who "carries" one copy of an autosomal recessive gene is usually not aware they carry the gene, because they do not show any signs of the disease or condition. It is estimated that all people carry about five or more recessive genes that cause genetic diseases or conditions. Usually a person does not know they carry a recessive gene unless they have the disease in their family, or if they have had an affected child.

What are autosomal recessive disorders?

Mutations (or changes in the DNA that codes for a gene) have occurred over time in different parts of the world. Anyone can carry virtually any type of recessive gene; however, there may be certain ethnic groups more likely to carry certain recessive genes, because of where the mutation originated. For example, the gene which causes Tay-Sachs disease is found most commonly in persons of Ashkenazi Jewish descent (because the mutation is thought to have originated in this area of eastern Europe), but can also be seen in persons who are not Ashkenazi.

What are some of the different types of autosomal recessive disorders?

Examples of autosomal recessive disorders include cystic fibrosis, sickle cell anemia, and Tay-Sachs disease.

Cystic fibrosis (CF)

Cystic fibrosis is one of the most common inherited single gene disorders in Caucasians. About one in 3,000 Caucasian babies is born with CF and about one in 25 Caucasians of northern European descent carries the gene for CF. People with CF secrete abnormal body fluids, including unusual sweat and a thick mucus which prevents the body from properly cleansing the lungs. The mucus interrupts the function of vital organs and leads to chronic infections. Classic CF also involves the pancreas and causes decreased absorption of essential nutrients. Life expectancy has improved, but, ultimately, death most often occurs from respiratory failure. Other people with variants of CF may have only lung involvement, sinusitis, or infertility.

Sickle cell anemia (SC)

Sickle cell anemia is one of the most common, inherited single gene disorders in African-Americans. About one in 500 African-American babies is born with SC, and about one in 12 African-American people carries the gene for SC. Sickle cell disease involves the red blood cells, or hemoglobin, and their ability to carry oxygen. Normal hemoglobin cells are smooth, round, and flexible, like the letter "O," so they can move through the vessels in our bodies easily. Sickle cell hemoglobin cells are stiff and sticky, and form into the shape of a sickle, or the letter "C" when they lose their oxygen. These sickle cells tend to cluster together and cannot easily move through the blood vessels. The cluster causes a blockage and stops the movement of healthy, normal oxygen carrying blood. This blockage is what causes the painful and damaging complications of sickle cell disease.

Sickle cells only live for about 15 days, whereas normal hemoglobin cells can live up to 120 days. Also, sickle cells risk being destroyed by the spleen because of their shape and stiffness. The spleen is an organ that helps filter the blood of infections. Sickled cells get "stuck" in this filter and die. Due to the decreased number of hemoglobin cells circulating in the body, a person with sickle cell is chronically anemic. The spleen also suffers damage from the sickled cells blocking healthy oxygen carrying cells. After repeated blockages, the spleen is very small and does not work properly. Without a functioning spleen, these individuals are more at risk for infections. Infants and young children are at risk for life-threatening infections. Treatment includes prompt emergency care for fevers and infections, appropriate vaccinations, penicillin, and management of anemia.

Tay-Sachs disease

Tay-Sachs disease is a fatal disorder in children (usually by age 5) that causes a progressive degeneration of the central nervous system. It is caused by the absence of an enzyme called hexosaminidase A (or hex A). Without hex A, a fatty substance builds up on the nerve cells in the body, particularly the brain. The process begins early in pregnancy when the baby is developing, but is not apparent until several months after the birth. To date, there is no cure for Tay-Sachs. Dr. Tay and Dr. Sachs, who originally described this condition, noted that most Tay-Sachs babies were usually of eastern European Jewish origin. About one in 30 persons of Ashkenazi Jewish ancestry carries the Tay-Sachs gene.