with adult-onset familial hemophagocytic lymphohistiocytosis Hypomorphic mutations in PRF1, MUNC13-4, and STXBP2 are associated

Abstract Familial hemophagocytic lymphohistiocytosis is a rare primary immunodeficiency disorder, characterized by defects in cell-mediated cytotoxicity that results in fever, hepatosplenomegaly, and cytopenias. Familial HLH is well recognized in children but rarely diagnosed in adults. We conducted a retrospective review of genetic and immunological test results in patients who developed HLH in their adulthood. 1531 patients with a clinical diagnosis of HLH were included in this study; 175 patients were 18 years or older. Missense and splice site sequence variants in PRF1, MUNC13-4, and STXBP2 were found in 25 (14%) of the adult patients. The A91V-PRF1 genotype was found in 12 of these patients (48%). The preponderance of hypomorphic mutations in FHL-causing genes correlates with the later-onset clinical symptoms and the more indolent course in adult patients. Late-onset FHL occurs more commonly than previously suspected. Keywords: Familial hemophagocytic lymphohistiocytosis, HLH, adult FHL, PRF1, MUNC13-4, STXBP2, mutation, variant, A91V, NK-cell, cytotoxicity From bloodjournal.hematologylibrary.org by guest on October 25, 2012. For personal use only.