1. Primary Immunodeficiencies Unit, Hospital de Dona Estefânia, Centro Hospitalar de Lisboa Central, EPE, Lisboa;
2. CEDOC - Chronic Diseases Research Center, NOVA Medical School, Lisboa, Portugal
3. Childhood Cancer Research Unit, Karolinska University Hospital Solna, Stockholm, Sweden;
4. Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
17th Biennial Meeting of the European Society for Immunodeficiencies (ESID), 2016, 21–24/09/2016, Barcelona, Spain (Poster)
Background: X-linked lymphoproliferative disease (XLP) is a rare primary immunodeficiency characterized by susceptibility to severe EBV infection. XLP-1 is caused by a mutation in SH2D1A which encodes the intracellular adaptor molecular SAP. It regulates signal transduction pathways downstream of the SLAM family of surface receptors to control CD4+ T cell (and B cells), CD8+ T cell and NK cell function. It can present as fulminant HLH, hypogammaglobulinemia, auto-immunity or lymphoproliferation.
Case Presentation: A 14-year-old male with a 4-months history of abdominal pain and weight loss. He presented tenderness in the right lower quadrant. The CT scan and colonoscopy revealed the presence of a vegetant mass in the ileocaecal transition, later characterized as an EBV-positive Burkitt lymphoma. He had an older brother who had died in 1995 at the age of 2 with fulminant EBV-HLH. This prompted investigation of underlying XLP: he had severe hypogammaglobulinemia, he had no switched memory B-cells and no NKT cells, thus allowing a presumptive diagnosis of SAP deficiency (XLP-1). Despite normal SAP expression, as measured by flow-cytometry, sequencing of SH2D1A revealed a hemizygous mutation (c.201G>A). The mutation does not affect the amino acid sequence (p.Glu67Glu), but disrupts a slice site, causing skipping of exon 2. The patient received CHOP therapy directed to Burkitt lymphoma as well as IGIV substitution, while he waits for HSCT.
Conclusion: Recognition by paediatricians of the different phenotypes of XLP is extremely important to allow an early multidisciplinary management of the disease, which is often fatal.
Palavras-chave: XLP, SAP, EBV, Lymphoma, Adolescent