Familial hemophagocytic lymphohistiocytosis with the MUNC13-4 mutation: a case report.
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.
Mizumoto
Hiroshi
H
Department of Pediatrics, Kitano Hospital, The Tazuke Kofukai Medical Institute, 2-4-20 Ohgimachi, Kita-ku, Osaka, 530-8480, Japan.
Hata
Daisuke
D
Yamamoto
Ken
K
Shirakawa
Ryutaro
R
Kumakura
Akira
A
Shiota
Mitsutaka
M
Yokoyama
Atsushi
A
Matsubara
Hiroshi
H
Kobayashi
Michihiro
M
Nishikomori
Ryuta
R
Adachi
Soichi
S
Nakahata
Tatsutoshi
T
Kita
Toru
T
Horiuchi
Hisanori
H
Yasukawa
Masaki
M
Ishii
Eiichi
E
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D016298:Hematopoietic Cell Growth Factors; D015395:Histocompatibility Antigens Class I; D006801:Humans; D007223:Infant; D051359:Lymphohistiocytosis, Hemophagocytic / Q000097:blood / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*
D016298:Hematopoietic Cell Growth Factors; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; C032907:Q surface antigens; C507969:UNC13D protein, human