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: 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
• Journal: European journal of pediatrics (Eur J Pediatr) Vol. 165 Issue 6 Pg. 384-8 (Jun 2006) ISSN: 0340-6199 [Print] Germany
• PMID: 16416131 (Publication Type: Case Reports, Journal Article)

Chemical References

• Hematopoietic Cell Growth Factors
• Histocompatibility Antigens Class I
• Membrane Proteins
• Q surface antigens
• UNC13D protein, human

Topics

• CD8-Positive T-Lymphocytes (immunology)
• Cytotoxicity, Immunologic
• Hematopoietic Cell Growth Factors
• Histocompatibility Antigens Class I
• Humans
• Infant
• Lymphohistiocytosis, Hemophagocytic (blood, genetics)
• Male
• Membrane Proteins (genetics)