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

• Published in: European journal of pediatrics 2006-06, Vol.165 (6), p.384-388
• Main Authors: MIZUMOTO, Hiroshi, HATA, Daisuke, ADACHI, Soichi, NAKAHATA, Tatsutoshi, KITA, Toru, HORIUCHI, Hisanori, YASUKAWA, Masaki, ISHII, Eiichi, YAMAMOTO, Ken, SHIRAKAWA, Ryutaro, KUMAKURA, Akira, SHIOTA, Mitsutaka, YOKOYAMA, Atsushi, MATSUBARA, Hiroshi, KOBAYASHI, Michihiro, NISHIKOMORI, Ryuta
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Bone marrow, stem cells transplantation. Graft versus host reaction; CD8-Positive T-Lymphocytes - immunology; Cytotoxicity, Immunologic; General aspects; Hematopoietic Cell Growth Factors; Histocompatibility Antigens Class I; Humans; Infant; Lymphohistiocytosis, Hemophagocytic - blood; Lymphohistiocytosis, Hemophagocytic - genetics; Male; Medical sciences; Membrane Proteins - genetics; Transfusions. Complications. Transfusion reactions. Cell and gene therapy
• ISSN: 0340-6199; 1432-1076
• DOI: 10.1007/s00431-005-0065-0

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.