X-linked lymphoproliferative disease due to XIAP deficiency

X-linked lymphoproliferative disease due to XIAP deficiency is a condition caused by changes in the XIAP gene, leading to a deficient or absent protein that normally helps regulate cell death. This defect can result in severe immune dysregulation, with symptoms that reflect excessive inflammatory responses and impaired control of immune activation. It primarily affects males due to its X-linked pattern of inheritance and is considered very rare, meaning it affects fewer than 1 in a million people. The condition is characterized by a range of serious clinical features that require careful management by healthcare professionals.

Individuals with this condition frequently experience signs of immune system overactivity. Common clinical features, seen in a majority of affected individuals, include hepatitis, hypertriglyceridemia, hypofibrinogenemia, increased circulating ferritin concentration, splenomegaly, and fever. In a somewhat smaller proportion of cases, hemophagocytosis is observed. Not all individuals experience all features, and severity varies considerably, making each presentation unique.

This condition results from pathogenic variants in the XIAP gene, which encodes a protein involved in inhibiting cell death processes. Disruption of this gene impairs the body’s ability to regulate immune cell survival, leading to an abnormal and often excessive inflammatory response. The condition follows an X-linked pattern of inheritance, meaning it almost exclusively affects males, while female carriers may experience symptoms due to skewed X-inactivation and should discuss monitoring with their healthcare provider. Genetic counseling is recommended for families to understand the inheritance and implications for future family planning. Associated genes include XIAP.