X-linked lymphoproliferative disorder and its causes

X-linked lymphoproliferative type 1 (XLP1) disorder is a rare immune condition
that affects around 1 in every 1 million males. In affected individuals, the body
cannot properly regulate an important type of white blood cell (lymphocytes)
in response to a viral infection, usually the Epstein-Barr virus that causes
glandular fever. The resulting excessive number of lymphocytes is known as
lymphoproliferation.

Causes of XLP1

XLP1 is caused by a mutation (change) in a gene named SH2D1A, which is important for producing a protein that regulates cells of the immune system, known as lymphocytes. This protein – called SAP (short for ‘SLAM associated protein’) – may be absent or abnormal so that it affects the development of specific lymphocytes called Natural Killer (NK) cells and the self-destruct pathway when cells are no longer needed.

Inheritance and XLP1

In many cases, XLP1 is an inherited condition, meaning it is passed on in families in the same way that physical characteristics, such as eye colour, are passed from parent to child. It is caused by a mutation (change) in a child’s genetic make-up. Specialists in genetics and genetic counselling are on hand to talk through the inheritance of XLP1 with you if needed, and PID UK has a separate information leaflet devoted to the genetics of primary immunodeficiency, available at
www.piduk.org/static/media/up/geneticaspectsofpid.pdf

X-linked disorders, such as XLP1, are the result of mutations in genes on the X
chromosome and almost exclusively affect males. It is very rare for a female to
develop symptoms of XLP1. A female who has a mistake on one of her two X
chromosomes also has a normal X chromosome, which compensates for the
abnormal one. This means that in almost all such situations, the female is healthy
but is a ‘carrier’. A male who inherits an X chromosome carrying a mutation does
not have a second X chromosome to compensate, so may be affected by an
‘X-linked recessive’ disorder.

Sometimes mutations can just happen by chance (sporadically) and are not
inherited from parents.