XIAP and its causes

X-linked inhibitor of apoptosis protein (XIAP) deficiency is a rare, inherited immunodeficiency that occurs almost exclusively in boys. Sometimes it is called X-linked lymphoproliferative type 2 disorder (XLP2). It was first recognised in 2006 and since then about 100 boys have been identified as having the disease.

What causes XIAP deficiency?

XIAP deficiency is caused by a mutation (change) in the XIAP gene that reduces its protein function. Normally, the XIAP protein does an important job in regulating the body’s immune response but, if the XIAP protein does not work, excessive
inflammation and damage can occur.

XIAP deficiency is an example of an X-linked disorder, which means that it almost exclusively affects males. This is because the XIAP gene is on the X chromosome. Females have two X chromosomes, so a problem in one copy of the XIAP gene can be compensated for by the second copy. Such females are healthy carriers
of XIAP deficiency. As boys have only one X chromosome, there is no second X chromosome to compensate if they inherit the abnormal copy of the XIAP gene, resulting in disease.

Sometimes the change can also occur as a ‘new mutation’ that has developed ‘out of the blue’ or sporadically, in which case there is no previous family history. More information about genetics is available in this PID UK leaflet.