Abstract
Familial hemophagocytic lymphohistiocytosis (HLH) is a fatal autosomal recessive disorder resulting in an exaggerated and ineffective immune response. Genetic defects in familial HLH can lead to the impaired function of the secretory lysosome-dependent exocytosis pathway. We report an STXBP2 homozygous missense mutation c.1139A>G, p.(Gln380Arg) consistent with a genetic diagnosis of familial hemophagocytic lymphohistiocytosis type 5 associated with chronic diarrhea in a seven-year-old girl. She was diagnosed with HLH and achieved remission by the HLH-2004 protocol and allogeneic matched bone marrow transplantation (BMT) from her sibling. However, six years later, she had a relapse of HLH, which required a second BMT. Ever since then, she continued to have persistent chronic watery diarrhea and failure to thrive. Patients with familial HLH type 5 due to STXBP2 gene mutation can manifest as either with or without chronic diarrhea. This unusual relationship directs toward a specific gene mutation of STXBP2 as the cause of chronic diarrhea in familial HLH. The prevalence of familial HLH in Saudi Arabia is underestimated. Due to the high rate of consanguinity and the local customs of marrying within the same community, clinicians should consider familial HLH as a cause of persistent, unexplained, chronic diarrhea among the pediatric age group.