title: Fatal sibling cases of familial hemophagocytic lymphohistiocytosis (FHL) with MUNC13-4 mutations: case reports.
abstract: The authors report here sibling cases of familial hemophagocytic lymphohistiocytosis (FHL) type 3 that took fatal courses despite intensive treatment. The older brother achieved remission by immunochemotherapy, but a central nervous system lesion occurred before the introduction of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The patient died on day +1 of allo-HSCT due to progression of the disease. The younger brother developed symptoms of hemophagocytic lymphohistiocytosis mimicking neonatal hemochromatosis at birth. He died without a chance to receive allo-HSCT. Both siblings showed low natural killer cell (NK) activity and the compound heterozygous Munc13-4 gene mutations 1596+1 and 1723insA were identified postmortem in the younger brother. With recent progress in the molecular diagnosis of FHL, prompt and most appropriate therapeutic measures should be introduced to improve the prognosis of FHL patients.
authors.affiliation: Department of Pediatric Health, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan. c0530319@kiban.md.tsukuba.ac.jp
authors.forename: Tomohei
authors.initials: T
authors.lastname: Nakao
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimizu
authors.forename: Takashi
authors.initials: T
authors.lastname: Fukushima
authors.forename: Makoto
authors.initials: M
authors.lastname: Saito
authors.forename: Miho
authors.initials: M
authors.lastname: Okamoto
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Sugiura
authors.forename: Ken
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Ikuyo
authors.initials: I
authors.lastname: Ueda
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Imashuku
authors.forename: Chie
authors.initials: C
authors.lastname: Kobayashi
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Koike
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsuchida
authors.forename: Ryo
authors.initials: R
authors.lastname: Sumazaki
authors.forename: Akira
authors.initials: A
authors.lastname: Matsui
mesh_terms: D002493:Central Nervous System Diseases / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D003937:Diagnosis, Differential; D017809:Fatal Outcome; D018380:Hematopoietic Stem Cell Transplantation; D006432:Hemochromatosis / Q000175:diagnosis / Q000235:genetics / Q000473:pathology / Q000628:therapy; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D051359:Lymphohistiocytosis, Hemophagocytic / Q000150:complications / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D035781:Siblings; D014184:Transplantation, Homologous
chemical_list: D008565:Membrane Proteins; C507969:UNC13D protein, human