Clinical and epidemiologic studies of familial hemophagocytic lymphohistiocytosis in Japan

E. Ishii, Shoichi Ohga, M. Tanimura, S. Imashuku, M. Sako, S. Mizutani, S. Miyazaki

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Background and Procedure. The etiology of familial hemophagocytic lymphohistiocytosis (FHL), which is characterized by fever, hepatosplenomegaly, pancytopenia, and coagulopathy, remains unknown. We analyzed 43 FHL patients, all with affected siblings, in 18 families who were identified during the period 1986-1995 in Japan. Results. The presence of consanguinity was evident in two families (11%). The majority of families lived in western Japan, where the frequency of consanguineous marriage is high. The incidence of FHL was significantly higher in the western island, Kyushu, than in other areas. The segregation ratio calculated for these families was 0.35 by the Weinberg proband method, showing the autosomal- recessive inheritance of the disease. Since the diagnosis of an FHL patient without affected siblings (sporadic case) is quite difficult, we calculated the possible number of sporadic cases; approximately 122 patients could be identified as sporadic FHL cases during the same period in Japan. Most of the clinical and laboratory findings were not distinguishable from those of other types of lymphohistiocytosis. However, atypical lymphoid cells with azurophilic granules in peripheral blood were observed in half of the patients at diagnosis, suggesting the clinical importance of this parameter for early diagnosis. Despite intensive therapy, the prognosis of FHL was extremely poor; but 4 of the 8 patients who have survived had received bone marrow transplantation (BMT), indicating the effectiveness of BMT for this disorder. Conclusions. The distribution of FHL in areas of highly frequent consanguineous marriage and the segregation analysis indicated a genetic factor in FHL. The identification of the genes for FHL is expected to contribute to a cure for this disorder, and might also enable FHL carrier detection and donor selection for BMT.

Original languageEnglish
Pages (from-to)276-283
Number of pages8
JournalMedical and Pediatric Oncology
Volume30
Issue number5
DOIs
Publication statusPublished - Apr 29 1998
Externally publishedYes

Fingerprint

Hemophagocytic Lymphohistiocytosis
Epidemiologic Studies
Japan
Bone Marrow Transplantation
Marriage
Siblings
Clinical Studies
Consanguinity
Donor Selection
Pancytopenia
Islands
Early Diagnosis
Fever
Lymphocytes

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Oncology
  • Cancer Research

Cite this

Clinical and epidemiologic studies of familial hemophagocytic lymphohistiocytosis in Japan. / Ishii, E.; Ohga, Shoichi; Tanimura, M.; Imashuku, S.; Sako, M.; Mizutani, S.; Miyazaki, S.

In: Medical and Pediatric Oncology, Vol. 30, No. 5, 29.04.1998, p. 276-283.

Research output: Contribution to journalArticle

Ishii, E. ; Ohga, Shoichi ; Tanimura, M. ; Imashuku, S. ; Sako, M. ; Mizutani, S. ; Miyazaki, S. / Clinical and epidemiologic studies of familial hemophagocytic lymphohistiocytosis in Japan. In: Medical and Pediatric Oncology. 1998 ; Vol. 30, No. 5. pp. 276-283.
@article{c847089a274c4926aec786af37f56ca9,
title = "Clinical and epidemiologic studies of familial hemophagocytic lymphohistiocytosis in Japan",
abstract = "Background and Procedure. The etiology of familial hemophagocytic lymphohistiocytosis (FHL), which is characterized by fever, hepatosplenomegaly, pancytopenia, and coagulopathy, remains unknown. We analyzed 43 FHL patients, all with affected siblings, in 18 families who were identified during the period 1986-1995 in Japan. Results. The presence of consanguinity was evident in two families (11{\%}). The majority of families lived in western Japan, where the frequency of consanguineous marriage is high. The incidence of FHL was significantly higher in the western island, Kyushu, than in other areas. The segregation ratio calculated for these families was 0.35 by the Weinberg proband method, showing the autosomal- recessive inheritance of the disease. Since the diagnosis of an FHL patient without affected siblings (sporadic case) is quite difficult, we calculated the possible number of sporadic cases; approximately 122 patients could be identified as sporadic FHL cases during the same period in Japan. Most of the clinical and laboratory findings were not distinguishable from those of other types of lymphohistiocytosis. However, atypical lymphoid cells with azurophilic granules in peripheral blood were observed in half of the patients at diagnosis, suggesting the clinical importance of this parameter for early diagnosis. Despite intensive therapy, the prognosis of FHL was extremely poor; but 4 of the 8 patients who have survived had received bone marrow transplantation (BMT), indicating the effectiveness of BMT for this disorder. Conclusions. The distribution of FHL in areas of highly frequent consanguineous marriage and the segregation analysis indicated a genetic factor in FHL. The identification of the genes for FHL is expected to contribute to a cure for this disorder, and might also enable FHL carrier detection and donor selection for BMT.",
author = "E. Ishii and Shoichi Ohga and M. Tanimura and S. Imashuku and M. Sako and S. Mizutani and S. Miyazaki",
year = "1998",
month = "4",
day = "29",
doi = "10.1002/(SICI)1096-911X(199805)30:5<276::AID-MPO3>3.0.CO;2-C",
language = "English",
volume = "30",
pages = "276--283",
journal = "Pediatric Blood and Cancer",
issn = "1545-5009",
publisher = "Wiley-Liss Inc.",
number = "5",

}

TY - JOUR

T1 - Clinical and epidemiologic studies of familial hemophagocytic lymphohistiocytosis in Japan

AU - Ishii, E.

AU - Ohga, Shoichi

AU - Tanimura, M.

AU - Imashuku, S.

AU - Sako, M.

AU - Mizutani, S.

AU - Miyazaki, S.

PY - 1998/4/29

Y1 - 1998/4/29

N2 - Background and Procedure. The etiology of familial hemophagocytic lymphohistiocytosis (FHL), which is characterized by fever, hepatosplenomegaly, pancytopenia, and coagulopathy, remains unknown. We analyzed 43 FHL patients, all with affected siblings, in 18 families who were identified during the period 1986-1995 in Japan. Results. The presence of consanguinity was evident in two families (11%). The majority of families lived in western Japan, where the frequency of consanguineous marriage is high. The incidence of FHL was significantly higher in the western island, Kyushu, than in other areas. The segregation ratio calculated for these families was 0.35 by the Weinberg proband method, showing the autosomal- recessive inheritance of the disease. Since the diagnosis of an FHL patient without affected siblings (sporadic case) is quite difficult, we calculated the possible number of sporadic cases; approximately 122 patients could be identified as sporadic FHL cases during the same period in Japan. Most of the clinical and laboratory findings were not distinguishable from those of other types of lymphohistiocytosis. However, atypical lymphoid cells with azurophilic granules in peripheral blood were observed in half of the patients at diagnosis, suggesting the clinical importance of this parameter for early diagnosis. Despite intensive therapy, the prognosis of FHL was extremely poor; but 4 of the 8 patients who have survived had received bone marrow transplantation (BMT), indicating the effectiveness of BMT for this disorder. Conclusions. The distribution of FHL in areas of highly frequent consanguineous marriage and the segregation analysis indicated a genetic factor in FHL. The identification of the genes for FHL is expected to contribute to a cure for this disorder, and might also enable FHL carrier detection and donor selection for BMT.

AB - Background and Procedure. The etiology of familial hemophagocytic lymphohistiocytosis (FHL), which is characterized by fever, hepatosplenomegaly, pancytopenia, and coagulopathy, remains unknown. We analyzed 43 FHL patients, all with affected siblings, in 18 families who were identified during the period 1986-1995 in Japan. Results. The presence of consanguinity was evident in two families (11%). The majority of families lived in western Japan, where the frequency of consanguineous marriage is high. The incidence of FHL was significantly higher in the western island, Kyushu, than in other areas. The segregation ratio calculated for these families was 0.35 by the Weinberg proband method, showing the autosomal- recessive inheritance of the disease. Since the diagnosis of an FHL patient without affected siblings (sporadic case) is quite difficult, we calculated the possible number of sporadic cases; approximately 122 patients could be identified as sporadic FHL cases during the same period in Japan. Most of the clinical and laboratory findings were not distinguishable from those of other types of lymphohistiocytosis. However, atypical lymphoid cells with azurophilic granules in peripheral blood were observed in half of the patients at diagnosis, suggesting the clinical importance of this parameter for early diagnosis. Despite intensive therapy, the prognosis of FHL was extremely poor; but 4 of the 8 patients who have survived had received bone marrow transplantation (BMT), indicating the effectiveness of BMT for this disorder. Conclusions. The distribution of FHL in areas of highly frequent consanguineous marriage and the segregation analysis indicated a genetic factor in FHL. The identification of the genes for FHL is expected to contribute to a cure for this disorder, and might also enable FHL carrier detection and donor selection for BMT.

UR - http://www.scopus.com/inward/record.url?scp=0031954306&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031954306&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1096-911X(199805)30:5<276::AID-MPO3>3.0.CO;2-C

DO - 10.1002/(SICI)1096-911X(199805)30:5<276::AID-MPO3>3.0.CO;2-C

M3 - Article

VL - 30

SP - 276

EP - 283

JO - Pediatric Blood and Cancer

JF - Pediatric Blood and Cancer

SN - 1545-5009

IS - 5

ER -