This information describes the causes, treatment and diagnosis of the autoimmune lymphoproliferative syndrome (ALPS). The information has been produced jointly between Immunodeficiency UK, Great Ormond Street Hospital (GOSH) and the Great North Children’s Hospital.

Autoimmune lymphoproliferative syndrome (ALPS) is a rare genetic disorder associated with an excessive number of lymphocytes (lymphoproliferation), leading to enlargement of the lymph nodes (lymphadenopathy) and the spleen (splenomegaly). These lymphocytes can attack other parts of the body, particularly other blood cells, leading to autoimmune disease. This often shows up as anaemia or bruising.

ALPS results from mistakes (mutations) in one of a number of genes controlling how lymphocytes work. The most common gene affected is called FAS. These mutations cause the immune system to remain active even when no infection is present.

In most people with ALPS, a single copy of the faulty gene is passed on from one parent and a normal copy from the other parent. This is called autosomal dominant inheritance. Not all people with a faulty copy of the gene get ALPS. 40 per cent will not show any symptoms, so parents may not realise they carry the gene.

Sometimes new gene defects can occur ‘out of the blue’ in people with no history of the disorder in their family. If the genetic change occurs at the time of conception (in the eggs or sperm) it is called ‘sporadic’ and could be passed on to the next generation. If it occurs later in the development of the embryo, the gene mutation only affects blood cells and is called a ‘somatic’ variant, which cannot be passed on to future generations.

Rarely ALPS is inherited in an autosomal recessive pattern, which means that each parent passes on the altered gene but does not show any symptoms themselves. More information about the different patterns of inheritance and their implications for family planning can be found in our leaflet  Genetic aspects of primary immunodeficiency.

ALPS shows up in various ways at different stages of life. Lymphoproliferation affecting the spleen and lymph nodes generally appears during childhood. Parents may notice persistently enlarged glands in the child’s neck, armpits and groin. Often there are no other symptoms at this stage. 

Patients with ALPS are at increased risk of autoimmune disease, which occurs when the immune system malfunctions and attacks the body’s own tissues. A classic form of ALPS-related autoimmunity occurs when antibodies are formed that attack red blood cells (haemolytic anaemia) and platelets (thrombocytopenia), leading to tiredness and pallor, easy bruising and bleeding. This combination is called Evans syndrome. Other autoimmune diseases are much less common. 

Although most people with ALPS do not get lymphoma, ALPS is associated with an increased risk of this cancer of the white blood cells in adulthood. Lymphoma causes symptoms such as fever, fatigue, loss of appetite, weight loss or more marked enlargement of one or more lymph nodes. Doctors and patients will look out for these features so that appropriate tests and treatment can be arranged. 

The diagnosis of ALPS depends on recognition of suggestive clinical features, along with blood tests looking at the different types of lymphocytes, particularly some called double-negative T lymphocytes. There are many conditions that can cause similar symptoms and it is important that careful evaluation is performed to exclude any of these. Special tests, including genetic tests, are available if ALPS is strongly suspected.  

Complications of ALPS may need to be evaluated in their own right, for example, by scans or further blood tests. If lymphoma needs to be ruled out, a small biopsy of one of the lymph glands might be performed. 


Most patients do not require any treatment but just need to have the size of their glands and the number of blood cells present in a blood sample monitored regularly. Some patients might require medication to control the overgrowth of lymphocytes or autoimmune complications. This immunosuppressive treatment will be individualised for each patient’s problems and needs. For very severe disease, replacement of the abnormal lymphocytes by haematopoietic stem cell transplantation might be considered, but this is rare. 

The patient’s spleen can be quite big, but generally, this should be treated with medicines rather than splenectomy (surgical removal of the spleen). This is because the spleen does an important job in protecting us from serious infection. 

What does this mean for the future? 

Most people with ALPS have a good outlook. Symptoms often improve after puberty. The increased risk of lymphoma means patients should be followed up by a specialist. Genetic counselling, both for affected people and for family members, is important if the genetic cause is known. 

You can download our information booklet here.