Isolated congenital asplenia is a condition in which affected individuals are missing their spleen (asplenia) but have no other developmental abnormalities. While most individuals with this condition have no spleen at all, some people have a very small, nonfunctional spleen (hyposplenism).

The spleen plays an important role in the immune system. This organ is part of the lymphatic system, which produces and transports fluids and immune cells throughout the body. The spleen produces certain immune system cells called phagocytes that help remove bacteria from the blood in order to prevent infections. The spleen also stores particular blood cells that fight foreign invaders until they are needed and filters old blood cells for removal. Because people with isolated congenital asplenia lack these immune functions, they are highly susceptible to bacterial infections.

People with isolated congenital asplenia are prone to developing severe, recurrent infections. Infections most commonly affect the whole body (sepsis), the membrane covering the brain and spinal cord (meningitis), or the ears (otitis media). Infections are most often caused by the Streptococcus pneumoniae bacteria.

Without preventative care and proper treatment, the frequent infections caused by isolated congenital asplenia can be life-threatening.

About 40 percent of cases of isolated congenital asplenia are caused by mutations in a gene called RPSA. This gene provides instructions for making a protein called ribosomal protein SA, which is a component of ribosomes. Ribosomes are cellular structures that process the cell's genetic instructions to create proteins.

Each ribosome has two parts (subunits) called the large and small subunits. Ribosomal protein SA is one of several proteins that make up the small subunit. Within the ribosome, the function of the ribosomal protein SA is unclear. Research suggests that it helps the ribosome control the production of certain proteins, many of which are likely important for development before birth.

RPSA gene mutations are thought to reduce the amount of functional ribosomal protein SA. A shortage of the normal protein likely impairs the assembly of ribosomes, but the specific effects of the mutations are not known. It is unclear why RPSA gene mutations appear to solely affect development of the spleen.

When isolated congenital asplenia is not caused by mutations in the RPSA gene, the cause of the condition is unknown.

Normal Function

The RPSA gene provides instructions for making a protein called ribosomal protein SA, which is one of approximately 80 different ribosomal proteins. These proteins come together to form structures called ribosomes. Ribosomes process the cell's genetic instructions to create proteins.

Each ribosome is made up of two parts (subunits) called the large subunit and the small subunit. Ribosomal protein SA is part of the small subunit.

The specific roles of each of the ribosomal proteins within the ribosome are not entirely understood. Some ribosomal proteins are involved in the assembly or stability of ribosomes. Others help carry out the ribosome's main function of building new proteins. Research suggests that ribosomal protein SA helps the ribosome control the production of certain proteins, many of which are likely important for development before birth.

Health Conditions Related to Genetic Changes

Isolated congenital asplenia

At least 20 RPSA gene mutations have been identified in individuals with isolated congenital asplenia. People with this condition do not have a spleen but have no other developmental abnormalities. The spleen plays an important role in the immune system. Without this organ, affected individuals are highly susceptible to bacterial infections, which can be life-threatening.

RPSA gene mutations are thought to reduce the amount of functional ribosomal protein SA. A shortage of the normal protein likely impairs the assembly of ribosomes, but the specific effects of the mutations are not known. It is unclear why RPSA gene mutations solely affect the development of the spleen.

Other Names for This Gene

• 40S Ribosomal Protein SA
• LAMBR
• Laminin Receptor
• LAMININ RECEPTOR 1
• laminin receptor 1, human
• LAMININ RECEPTOR, 67-KD
• Laminin Receptor-1
• LAMR1
• Lamr1 protein, human
• Ribosomal Protein SA Gene
• RPSA Gene

Genomic Location

Isolated congenital asplenia caused by mutations in the RPSA gene is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

In most cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene that occur during the formation of reproductive cells (eggs or sperm) in an affected individual's parent or in early embryonic development. These cases occur in people with no history of the disorder in their family.

For unknown reasons, some people with an RPSA gene mutation that has been associated with isolated congenital asplenia have a normal spleen. The condition is said to have incomplete penetrance because not everyone with an RPSA gene mutation develops the condition.

When the cause of isolated congenital asplenia is unknown, the inheritance of the condition is unclear.

The worldwide prevalence of isolated congenital asplenia is unknown. One population study done in France estimated that the condition occurs in 1 per 2 million newborns.