X-linked inhibitor of apoptosis (XIAP) deficiency, also known as X-linked lymphoproliferative syndrome type 2 (XLP2), occurs in about 1 in 5 million males [1] and is associated with development of hemophagocytic lymphohistiocytosis (HLH), splenomegaly and treatment-resistant Crohn’s disease [2][3]. Here we present the cases of two XLP2 siblings with lymphopenia, hepatosplenomegaly, recurrent infections, and refractory Crohn’s disease.