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Joana Freitas1, Maria do Carmo Pinto1, José Cabral2, Rui Alves3, Conceição Neves4, João Farela Neves4

1- Adolescence unit;
2- Paediatric Gastroenterology unit;
3- Paediatric Surgical unit;
4- Primary Immunodeficiencies Unit;

- Paediatric Unit, Hospital Dona Estefânia- CHLC, EPE. Lisbon, Portugal.
- Excellence in Pediatrics- Londres

X-linked lymphoproliferative disease (XLP) is a rare primary immunodeficiency characterized by susceptibility to severe Epstein-Barr virus (EBV) infection. XLP-1 is caused by a mutation in SH2D1A which encodes the intracellular adaptor molecular SAP, expressed mainly in T cells and NK cells. 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 hemophafocytic lymphohystiocytosis (HLH), hypogammaglobulinemia, auto-immunity or lymphoproliferation.
Clinical report
We describe a case of a 14-year-old male with a 4-months history of abdominal pain, weight loss and asthenia.  He presented tenderness in the right lower quadrant and the CT scan and colonoscopy revealed the presence of a vegetant mass in the ileocaecal transition. He was submitted to a 20 cm intestinal resection due to intestinal perforation. The histological examination led to the diagnosis of an EBV- positive Burkitt lymphoma. His family history was remarkable for the presence of an older brother who had died in 1995 at the age of 2 with fulminant EBV-HLH.  This prompted the investigation of underlying XLP: he had severe hypogammaglobulinemia, his serology for EBV was positive for VCA IgG but negative for EBNA, he had no switched memory B-cells and no NKT cells, thus allowing a presumptive diagnosis of SAP deficiency (XLP-1). The patient presented normal SAP expression but the genetic analysis of SH2D1A revealed a hemizygous mutation which alters splicing, but does not affect amino acid sequence, confirming the diagnosis of XLP-1. One older sister is carrier of the same mutation. The patient received CHOP therapy directed to Burkitt lymphoma as well as IGIV substitution, while he waits for hematopoietic stem cell transplantation.
Although the patient had a typical presentation of an intestinal lymphoma. Nevertheless, the familiar history of an early death in a boy following EBV infection raised the hypothesis of XLP, which was confirmed promptly, thus allowing proper management and counselling.
The recognition by the Paediatricians of the different phenotypes of XLP is extremely important to allow an early multidisciplinary management of the disease, which is often fatal.