The major clinical symptoms of ALPS result from lymphoproliferation, or the excessive production of a type of white blood cell called a lymphocyte, and autoimmune destruction of blood cells. Many people with ALPS experience a lessening or complete resolution of their autoimmune and lymphoproliferative symptoms in adulthood.
The main lymphoproliferative symptoms in ALPS are enlarged lymph nodes and spleen. While the spleen can be massive in some children, the National Institutes of Health team is aware of only one case of splenic rupture. The swollen lymph nodes in the neck, armpit, and groin are usually most noticeable. Sometimes, these enlarged lymph nodes are confused with cancer of the lymph gland, or lymphoma. Large, visible lymph nodes are normal for many people with ALPS. It also is normal for lymph nodes to change somewhat in size, shape, or feel over time. Such changes are usually not a lymphoma.
The main autoimmune issues in ALPS are related to reactions against components of blood.
- Anemia occurs when the body destroys its own red blood cells. This causes a feeling of weakness and fatigue.
- Thrombocytopenia occurs when the body attacks and destroys blood components called platelets. When platelet levels are low, the blood does not clot well, and bleeding cannot be stopped following minor injuries. Thrombocytopenia can lead to nosebleeds, gum bleeds, and bruises.
- Neutropenia occurs when the body destroys infection-fighting cells called neutrophils. A decrease in neutrophils increases the risk of infection, which can lead to symptoms such as mouth ulcers and slow wound healing.
ALPS-related autoimmunity sometimes targets organs, leading to conditions such as
- Hepatitis (inflammation of the liver)
- Glomerulonephritis (inflammation of the kidneys)
- Uveitis (inflammation of the iris in the eye).
People with ALPS have an increased risk of developing lymphoma. Up to age 40, people with ALPS have an approximately 20 percent risk of developing lymphoma. In other words, about 1 in 5 patients will develop ALPS lymphoma by the time they are 40. The risk continues past age 40, although the data on older age groups are limited. Thus, doctors should monitor patients with ALPS for symptoms of lymphoma, such as night sweats, fever, fatigue, weight loss, loss of appetite, and sudden lymph-node enlargement in one area. Although the lymphoma risk for people with ALPS is much higher than that for the general population, most people with ALPS never develop lymphoma.
The diagnosis of ALPS is based on clinical findings, laboratory findings, and identification of mutations in genes, such as FAS, that affect the programmed destruction of cells (apoptosis). Clinical findings that suggest ALPS include
- Non-cancerous swelling of the lymph nodes (lymphadenopathy) that lasts for more than six months
- Autoimmune disease, especially against blood cells
- Cancer of the lymph nodes (lymphoma)
- Family history of ALPS or ALPS-like features
One prominent finding is an elevated level of CD4- and CD8-negative T lymphocytes, called double-negative T cells. Lab tests can confirm defects in apoptosis of lymphocytes, which is highly suggestive of ALPS. Additionally, an increase in serum vitamin B12 can indicate lymphoproliferation in the form of ALPS caused by mutations in the FAS gene (ALPS-FAS). People with ALPS-FAS tend to have much higher B12 levels than do healthy people, a finding made by NIAID scientists in 2014.
Doctors may perform additional blood tests to help diagnose ALPS. Other markers that may be elevated in ALPS include plasma interleukin-10; plasma interleukin-18; immunoglobulin subtypes IgG, IgA, and IgM; absolute monocyte count; absolute eosinophil count; anticardiolipin antibody; and antinuclear antibody. In contrast, people with ALPS often have abnormally low levels of HDL (high density lipoprotein) and total cholesterol.