LAUSR

To the Editor: X-linked lymphoproliferative disease (XLP) is a rare primary immunodeficiency characterized by the inability of the affected individual to clear Epstein-Barr virus (EBV) resulting in hemophagocytic lymphohistiocytosis (HLH) in 55% to 76% of male individuals carrying mutations in SH2D1A (XLP-1) or XIAP (XLP-2).1,2 Here, we reveal a novel SH2D1A mutation in a child with XLP. A 7-year-old Sudanese boy presented with a 3-week history of fever, lethargy, anorexia, and abdominal distension. His oldest brother died aged 7 months of an unspecified febrile illness. Examination revealed cervical lymphadenopathy and hepatosplenomegaly. Initial blood tests showed a normal full blood count, and elevated erythrocyte sedimentation rate of 57mm/h (<15mm/h), lactate dehydrogenase level of 1980U/L (420 to 750U/L), and ferritin concentration level of 1510 μg/ L (15 to 100 μg/L). Liver function tests were deranged, with bilirubin concentration of 41 μmol/L (<20 μmol/L), alanine transaminase level of 349U/L (<30U/L), aspartate transaminase of 575U/L (<40U/L), γ-glutamyl transferase of 251U/L (<25U/L), and alkaline phosphatase of 607U/L (120 to 440U/L). Infectious hepatitis was considered among the differential diagnoses, with screening revealing active EBV infection (viral load 3.99×104 copies/mL). Subsequent investigations identified hypergammaglobulinemia with an immunoglobulin (Ig) G level of 22.4 g/L (6.0 to 12.3 g/L), IgA of 5.31 g/ L (0.33 to 2.0 g/L), and IgM of 13.32 g/L (0.46 to 2.0 g/L); elevated triglyceride concentration of 3.6mmol/L (<1.7mmol/L), hypofibrinogenemia of 0.7 g/L (2.0 to 4.0 g/L), and hemophagocytosis on bone marrow aspirate were noted. Given the constellation of clinical and laboratory features, a diagnosis of EBV-driven HLH was made. XLP was confirmed following the sequencing of the SH2D1A gene, which revealed a hemizygous missense mutation, c.1A>G, in exon 1 resulting in an amino acid (aa) substitution, p.