Fatal sibling cases of familial hemophagocytic lymphohistiocytosis (FHL) with MUNC13-4 mutations: case reports.
The authors report here sibling cases of familial hemophagocytic lymphohistiocytosis (FHL) type 3 that took fatal courses despite intensive treatment. The older brother achieved remission by immunochemotherapy, but a central nervous system lesion occurred before the introduction of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The patient died on day +1 of allo-HSCT due to progression of the disease. The younger brother developed symptoms of hemophagocytic lymphohistiocytosis mimicking neonatal hemochromatosis at birth. He died without a chance to receive allo-HSCT. Both siblings showed low natural killer cell (NK) activity and the compound heterozygous Munc13-4 gene mutations 1596+1 and 1723insA were identified postmortem in the younger brother. With recent progress in the molecular diagnosis of FHL, prompt and most appropriate therapeutic measures should be introduced to improve the prognosis of FHL patients.
Nakao
Tomohei
T
Department of Pediatric Health, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan. c0530319@kiban.md.tsukuba.ac.jp
Shimizu
Takashi
T
Fukushima
Takashi
T
Saito
Makoto
M
Okamoto
Miho
M
Sugiura
Masatoshi
M
Yamamoto
Ken
K
Ueda
Ikuyo
I
Imashuku
Shinsaku
S
Kobayashi
Chie
C
Koike
Kazutoshi
K
Tsuchida
Masahiro
M
Sumazaki
Ryo
R
Matsui
Akira
A
D002493:Central Nervous System Diseases / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D003937:Diagnosis, Differential; D017809:Fatal Outcome; D018380:Hematopoietic Stem Cell Transplantation; D006432:Hemochromatosis / Q000175:diagnosis / Q000235:genetics / Q000473:pathology / Q000628:therapy; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D051359:Lymphohistiocytosis, Hemophagocytic / Q000150:complications / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D035781:Siblings; D014184:Transplantation, Homologous
D008565:Membrane Proteins; C507969:UNC13D protein, human