X-linked inhibitor of apoptosis (XIAP) deficiency, caused by X-linked inherited mutations in BIRC4, is an rare inherited immunodeficiency recognized as X-linked lymphoproliferative syndrome type 2. XIAP deficiency is mainly associated with EBV-associated hemophagocytic lymphohistiocytosis (HLH) phenotypes, and also considered as one of the genetic causes of very early onset inflammatory bowel disease(VEO-IBD). Genetic testing is crucial in diagnosing this syndrome. We report the clinical courses of a 5-year-old Korean boy with a recurrent diarrhea and anal abscess and his monozygotic twin with a HLH in a family with XIAP mutations. The first baby of the twin who presented with meconium peritonitis due to ileal atresia with perforation in the first day of life, followed by intractable colitis and malnutrition, was diagnosed as Crohn’s disease at 4-year old with recurrent episodes of fever and perianal abscess. He had a complicated disease course and remained unresponsive to medical therapy. The other developed HLH when he was 3-year old and chemotherapy was done. After several immunological, genetic and clinical investigations, Diagnostic Exome Sequencing of VEO-IBD and HLH associated genes revealed a causative mutation in XIAP. The further investigation of his twin brother and one of the older brother who became cerebral palsy after suffering from bacterial meningitis at 1-year old showed the same homozygous mutation at c.1332delG. A heterozygous mutation was found in his mother and no mutation was found in another brother and his father who were healthy. Genetic testing is essential to confirm the diagnosis of XIAP deficiency and detect the carrier of mutation. Comprehensive genetic analysis of XIAP mutation carriers and close surveillance of individuals at risk for XIAP deficiency syndrome may allow prompt diagnosis and effective treatments. This review aims to draw the attention of the pediatrician to XLP, which should be differentiated from other forms of HLH and consider in a wide range of clinical presentations.