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Spectrum of clinical presentations in familial hemophagocytic lymphohistiocytosis type 5 patients with mutations in STXBP2

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  • Marie Meeths
  • Miriam Entesarian
  • Waleed Al-Herz
  • Samuel C C Chiang
  • Stephanie M Wood
  • Wafa Al-Ateeqi
  • Francisco Almazan
  • Jaap J Boelens
  • Henrik Hasle
  • Marianne Ifversen
  • Bendik Lund
  • J Merlijn van den Berg
  • Britt Gustafsson
  • Hans Hjelmqvist
  • Magnus Nordenskjöld
  • Yenan T Bryceson
  • Jan-Inge Henter
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Hemophagocytic lymphohistiocytosis (HLH) is an often-fatal hyperinflammatory syndrome characterized by fever, hepatosplenomegaly, cytopenia, and in some cases hemophagocytosis. Here, we describe the mutation analysis, clinical presentation, and functional analysis of natural killer (NK) cells in patients with mutations in STXBP2 encoding Munc18-2, recently associated with familial HLH type 5. The disease severity among 11 persons studied here was highly variable and, accordingly, age at diagnosis ranged from 2 months to 17 years. Remarkably, in addition to typical manifestations of familial HLH (FHL), the clinical findings included colitis, bleeding disorders, and hypogammaglobulinemia in approximately one-third of the patients. Laboratory analysis revealed impairment of NK-cell degranulation and cytotoxic capacity. Interleukin-2 stimulation of lymphocytes in vitro rescued the NK cell-associated functional defects. In conclusion, familial HLH type 5 is associated with a spectrum of clinical symptoms, which may be a reflection of impaired expression and function of Munc18-2 also in cells other than cytotoxic lymphocytes. Mutations in STXBP2 should thus also be considered in patients with clinical manifestations other than those typically associated with HLH.
Original languageEnglish
JournalBlood
Volume116
Issue number15
Pages (from-to)2635-43
Number of pages9
ISSN0006-4971
DOIs
Publication statusPublished - 14 Oct 2010

ID: 32225411