Description
X-linked lymphoproliferative syndrome (XLP) was first described in 1975, and a clear clinical phenotype was defined. Many individuals are asymptomatic before the onset of fatal disease, such as fulminant infectious mononucleosis. Definition of mutations in affected individuals in the gene SH2D1A, which encodes the protein SAP, has facilitated diagnosis. However, no mutation can be found in at least a third of patients with a well defined clinical syndrome. A number of these do not express SAP protein, suggesting that there are mutations in promoter elements or other control genes. Increasing numbers of patients are now being defined with XLP, including those previously given other diagnoses such as haemophagocytic lymphohistiocytosis, common variable immune deficiency, lymphoma or aplastic anaemia. Careful follow up of these milder or atypical patients is required to elucidate the true spectrum and natural history of the disease.
