What does the research say about X-linked lymphoproliferative disease?
Drawing from reference databases
Cyrus has X-linked lymphoproliferative disease (XLP) caused by a pathogenic frameshift variant in XIAP (c.1045_1048del, p.Glu349ArgfsTer12). This deletion falls within the region of the XIAP protein required for interaction with DIABLO, disrupting a key regulatory function. Inferred
Core clinical picture
XLP is characterized by an abnormal immune response, particularly to Epstein-Barr virus (EBV, the virus that causes mono). The major risks are: GeneReviews
- Hemophagocytic lymphohistiocytosis (HLH): a life-threatening immune overactivation, often triggered by EBV infection, causing prolonged high fever, low blood counts, and liver/spleen enlargement. This is a medical emergency.
- Inflammatory bowel disease: in the XIAP subtype, this is a recognized feature, often resembling Crohn's disease.
Inheritance
XLP follows an X-linked recessive pattern, meaning it primarily affects males. OrphanetGeneReviews
How rare is it?
XLP is extremely rare; prevalence is less than 1 in 1,000,000 in Europe. Orphanet