Autoimmune lymphoproliferative syndrome (ALPS) is an autoimmune condition caused by an inherited defect in the immune system. Normally, the immune system attacks foreign invaders, such as bacteria. Antibodies are a component of the immune system that normally attack foreign invaders to help destroy them. In patients with ALPS, there are increased numbers of lymphocytes, which are a type of white blood cell that make antibodies. Some of the antibodies produced by the extra lymphocytes attack normal components of the body (such as red blood cells or platelets), causing them to malfunction.

Many patients with ALPS have a mutation, or error, in a gene called Fas. Individuals have two copies of most genes, and in 83% of patients with ALPS, at least one copy of the Fas gene appears to be defective. The Fas gene normally functions to cause specific cells to die (such as lymphocytes). A defect in the Fas gene could reduce the amount of cell death among lymphocytes after they are done fighting an infection, leading to higher numbers of lymphocytes that continue to create antibodies. These extra antibodies then begin to attack the body's normal components, resulting in ALPS. However, because some patients with ALPS do not have a defective Fas gene, researchers believe that additional genetic or environmental factors may lead to the disease.

Autoimmune lymphoproliferative syndrome (ALPS) is a newly described disease and many of the symptoms are not specific to just ALPS. Therefore, it may be difficult for a doctor to diagnose ALPS without knowledge of the disease and its symptoms.

Clinical exam: A diagnosis is often made based on a clinical examination to check for symptoms of the disease. Symptoms that a doctor may look for to diagnose ALPS include an enlarged spleen (due to more blood cells getting stuck there), enlarged lymph nodes, skin rash, and frequent nose bleeds.

Blood tests: Patients with ALPS often have reduced numbers of red blood cells and increased numbers of certain types of white blood cells. Blood may be drawn from patients to check for these signs of the disease.

Genetic tests: Most patients with ALPS have a mutation, or error, in a gene called Fas. In patients who exhibit symptoms of ALPS, genetic testing may be used to look for a mutation in Fas and help diagnose the condition.

Cellular assays: Experiments may be performed on the lymphocytes of patients who are suspected to have ALPS to confirm a diagnosis. The lymphocytes of most patients with ALPS undergo decreased levels of cellular death, due to a defect, or mutation, in the Fas gene. A patient's lymphocytes can be tested in a laboratory using a cellular assay, to determine if the lymphocytes undergo decreased levels of death due to this mutation.

Patients with autoimmune lymphoproliferative syndrome (ALPS) may have a wide spectrum of symptoms, depending on which component(s) of the body have been compromised by the immune system. In individuals with ALPS, antibodies commonly attack red blood cells, which transport oxygen throughout the body, or platelets, which help in clotting. However, the antibodies may attack cells in almost any location throughout the body, such as the skin, kidney, liver, or nerves. Additional symptoms that patients may experience are highly specific based on the other type(s) of cells that are attacked.

If the immune system attacks red blood cells, patients with ALPS may have a reduction in red blood cell number. Because red blood cells normally transport oxygen to other cells in the body, this may lead to fatigue or weakness. Symptoms that patients with ALPS may develop include an enlarged spleen (due to more blood cells getting stuck there) or enlarged lymph nodes.

If the immune system attacks platelets, patients with ALPS will have a reduction in the number of platelets. Platelets are blood cells that help with the process of clotting. A reduction in platelets may lead to bruises, nosebleeds, increased risk of hemorrhage (excessive bleeding), or the formation of small red or purple spots on the skin called petechiae.

Skin rashes are frequently observed in patients with ALPS, likely due to autoimmune attacks on the skin.

In some patients with ALPS, antibodies may attack other white blood cells that normally fight disease or infection. This can lead to a reduction in the numbers of white blood cells, leaving an individual more susceptible to bacterial infection. Common symptoms of a bacterial infection include fever, sweating, chills, and fast breathing.

Enlarged spleen: In individuals with autoimmune lymphoproliferative syndrome (ALPS), red blood cells and platelets are often attacked by excess antibodies. When the antibodies become attached to red blood cells or platelets, they may become stuck in the spleen, an organ that filters the blood by removing cells that are no longer needed. Patients with ALPS may have enlarged spleens because of the large numbers of red blood cells and platelets that become stuck there, and these individuals are at a higher risk of having a rupture in the spleen, a potentially life-threatening condition in which a large amount of blood spills out of the spleen into the body.

Swollen lymph nodes: White blood cells such as lymphocytes are normally stored in the body in small capsules called lymph nodes. Because patients with ALPS have increased numbers of white blood cells, they may develop swelling of the lymph nodes. There are a large number of lymph nodes under the cheeks, which may cause patients with ALPS to appear as though they have swollen faces.

Autoimmune diseases: Patients with ALPS have a greater risk of developing other autoimmune diseases. These may include Guillain-Barre syndrome (a condition in which the immune system attacks parts of the nervous system) and systemic lupus erythematosus (an inflammatory condition in which the immune system attacks the skin, joints, kidneys, lungs, or other parts of the body).

Lymphoma: Patients with ALPS have an increased risk of developing lymphoma, a type of cancer caused by an abnormal growth of lymphocytes.

Many patients with autoimmune lymphoproliferative syndrome (ALPS) have a mutation, or error in a gene called Fas. Individuals have two copies of most genes, and in 83% of patients with ALPS, at least one copy of the Fas gene appears to be defective. If an individual has a parent with one mutant Fas gene, that individual has a 50% chance of inheriting the mutant Fas gene. Individuals with a mutant Fas gene have an increased risk of developing ALPS. Because only one defective gene is needed for ALPS to develop, ALPS is considered an autosomal dominant inheritance condition. However, because not all individuals with a mutant Fas gene develop ALPS, researchers believe that additional genetic or environmental factors may be involved in the disease.