ALPS and its causes

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.

Causes of ALPS

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: www.piduk.org/whatarepids/geneticaspectsofpid