TY - JOUR
T1 - Familial hemophagocytic lymphohistiocytosis with the MUNC13-4 mutation
T2 - A case report
AU - Mizumoto, Hiroshi
AU - Hata, Daisuke
AU - Yamamoto, Ken
AU - Shirakawa, Ryutaro
AU - Kumakura, Akira
AU - Shiota, Mitsutaka
AU - Yokoyama, Atsushi
AU - Matsubara, Hiroshi
AU - Kobayashi, Michihiro
AU - Nishikomori, Ryuta
AU - Adachi, Soichi
AU - Nakahata, Tatsutoshi
AU - Kita, Toru
AU - Horiuchi, Hisanori
AU - Yasukawa, Masaki
AU - Ishii, Eiichi
PY - 2006/6
Y1 - 2006/6
N2 - 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.
AB - 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.
KW - Central nervous system complication
KW - Familial hemophagocytic lymphohistiocytosis
KW - MUNC13-4
KW - Stem cell transplantation
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U2 - 10.1007/s00431-005-0065-0
DO - 10.1007/s00431-005-0065-0
M3 - Article
C2 - 16416131
AN - SCOPUS:33646485093
VL - 165
SP - 384
EP - 388
JO - European Journal of Pediatrics
JF - European Journal of Pediatrics
SN - 0340-6199
IS - 6
ER -