Familial hemophagocytic lymphohistiocytosis with the MUNC13-4 mutation: A case report

Hiroshi Mizumoto, Daisuke Hata, Ken Yamamoto, Ryutaro Shirakawa, Akira Kumakura, Mitsutaka Shiota, Atsushi Yokoyama, Hiroshi Matsubara, Michihiro Kobayashi, Ryuta Nishikomori, Soichi Adachi, Tatsutoshi Nakahata, Toru Kita, Hisanori Horiuchi, Masaki Yasukawa, Eiichi Ishii

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)384-388
Number of pages5
JournalEuropean Journal of Pediatrics
Issue number6
Publication statusPublished - 2006 Jun
Externally publishedYes


  • Central nervous system complication
  • Familial hemophagocytic lymphohistiocytosis
  • MUNC13-4
  • Stem cell transplantation

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health


Dive into the research topics of 'Familial hemophagocytic lymphohistiocytosis with the MUNC13-4 mutation: A case report'. Together they form a unique fingerprint.

Cite this