title: Familial hemophagocytic lymphohistiocytosis with the MUNC13-4 mutation: a case report.
abstract: A 44-day-old male infant with familial hemophagocytic lymphohistiocytosis (FHL) associated with the MUNC13-4 mutation is reported. He presented with fever and poor feeding, lymphocytosis with thrombocytopenia and CSF pleocytosis without virological explanation. On the basis of progressive hyperferritinemia (1323 ng/ml), anemia (hemoglobin: 5.2 g/dl), hypertriglyceridemia (547 mg/dl) and increased LDH (1063 IU/l) with hemophagocytosis in the bone marrow, hemophagocytic lymphohistiocytosis was diagnosed. He showed a good response to corticosteroid therapy and the disease was stable for more than 5 months. Thereafter, he suffered from central nervous system complications, and successfully underwent unrelated cord blood stem cell transplantation. A remission was observed for more than 2 years, with mild mental retardation. Genetic analysis revealed that he had a compound heterozygous mutation of MUNC13-4; namely a novel 2163G>A mutation resulting in W721X, and 754-1G>C resulting in a premature stop codon in this gene. Western blot analysis showed the complete loss of the MUNC13-4 protein, whereas other molecules associated with the SNARE systems were detected at normal levels. Conclusion. FHL may have a broad clinical spectrum, and further analysis on its phenotype-genotype association is required to establish an appropriate treatment strategy, including immunochemotherapy and stem cell transplantation in the future.
authors.affiliation: Department of Pediatrics, Kitano Hospital, The Tazuke Kofukai Medical Institute, 2-4-20 Ohgimachi, Kita-ku, Osaka, 530-8480, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mizumoto
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hata
authors.forename: Ken
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Shirakawa
authors.forename: Akira
authors.initials: A
authors.lastname: Kumakura
authors.forename: Mitsutaka
authors.initials: M
authors.lastname: Shiota
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yokoyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsubara
authors.forename: Michihiro
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Ryuta
authors.initials: R
authors.lastname: Nishikomori
authors.forename: Soichi
authors.initials: S
authors.lastname: Adachi
authors.forename: Tatsutoshi
authors.initials: T
authors.lastname: Nakahata
authors.forename: Toru
authors.initials: T
authors.lastname: Kita
authors.forename: Hisanori
authors.initials: H
authors.lastname: Horiuchi
authors.forename: Masaki
authors.initials: M
authors.lastname: Yasukawa
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ishii
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D016298:Hematopoietic Cell Growth Factors; D015395:Histocompatibility Antigens Class I; D006801:Humans; D007223:Infant; D051359:Lymphohistiocytosis, Hemophagocytic / Q000097:blood / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*
chemical_list: D016298:Hematopoietic Cell Growth Factors; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; C032907:Q surface antigens; C507969:UNC13D protein, human