title: Unusual clinical presentations of familial hemophagocytic lymphohistiocytosis type-2.
abstract: BACKGROUND
  Mutations of PRF1 gene have been identified in familial hemophagocytic lymphohistiocytosis type-2 (FHL-2) patients, and it has been reported as the commonest gene defect causing FHL. Patients with severe perforin deficiency usually present within first 1 year of life and with severe clinical manifestations.
  
  
  METHODS
  We report 4 cases of severe perforin deficiency presenting with delayed onset and unusual clinical presentations viz., B-cell acute lymphoblastic leukemia, the Hodgkin lymphoma, tuberculosis, and the Still disease. Three of these 4 cases showed a common heterozygous missense mutation (p.Trp129Ser). Two of these patients expired because of uncontrolled hemophagocytic lymphohistiocytosis, one patient had 3 relapses while on therapy and one patient was in remission on maintenance therapy.
  
  
  CONCLUSIONS
  This study shows variety of clinical manifestations of perforin deficiency and although the onset of hemophagocytic lymphohistiocytosis is delayed in these patients, the outcome remains poor as in classical severe perforin deficiency patients.
authors.affiliation: Departments of *Pediatric Immunology and Leukocyte Biology †Department of Hematology, National Institute of Immunohaematology (ICMR), Parel, Mumbai, India.
authors.forename: Snehal
authors.initials: S
authors.lastname: Mhatre
authors.forename: Manisha
authors.initials: M
authors.lastname: Madkaikar
authors.forename: Farah
authors.initials: F
authors.lastname: Jijina
authors.forename: Kanjaksha
authors.initials: K
authors.lastname: Ghosh
mesh_terms: D001171:Arthritis, Juvenile / Q000175:diagnosis / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D006579:Heterozygote; D006689:Hodgkin Disease / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D051359:Lymphohistiocytosis, Hemophagocytic / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics; D014376:Tuberculosis / Q000175:diagnosis; D055815:Young Adult
chemical_list: C510468:PRF1 protein, human; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin