摘要
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 (1.323 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.
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 (1.323 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.
