Clinical characteristics and outcomes of chédiak-Higashi syndrome: A nationwide survey of Japan

Kozo Nagai, Fumihiro Ochi, Kiminori Terui, Miho Maeda, Shouichi Ohga, Hirokazu Kanegane, Toshiyuki Kitoh, Kazuhiro Kogawa, Nobuhiro Suzuki, Shigeru Ohta, Yasushi Ishida, Takayuki Okamura, Hiroshi Wakiguchi, Masaki Yasukawa, Eiichi Ishii

Research output: Contribution to journalArticle

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Abstract

Background: Chédiak-Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized by immunodeficiency, neurological dysfunction, and oculocutaneous albinism. Recently, several clinical CHS phenotypes have been reported. Here, we report results of a nationwide survey performed to clarify clinical characteristics and outcomes of CHS patients in Japan. Methods: Questionnaires were sent to 287 institutions to collect data regarding CHS patients diagnosed between 2000 and 2010, including results of lysosomal trafficking regulator (LYST) gene analysis. Cytotoxicity and degranulation activity of cytotoxic T lymphocytes were analyzed in available patient samples. Results: A total of 15 patients diagnosed with CHS were eligible for enrollment in this study. Of these, 10 (67%) had recurrent bacterial infections, five (33%) developed life-threatening hemophagocytic lymphohistiocytosis (HLH), and one patient had complicated malignant lymphoma. Hematopoietic stem cell transplantation (HSCT) was performed for six patients including three with HLH, and 10 of the enrolled patients have survived at the time of this writing. LYST analysis was performed for 10 patients; seven different mutations were detected in seven patients, whereas no mutation was identified in three patients. Cytotoxicity and degranulation activity were impaired in patients with and without LYST mutation. Discussion: Results of this survey indicate that one or two patients with CHS were newly diagnosed each year in Japan. The incidence of HLH was not as high as expected. Mutations of genes other than LYST were suspected in some cases. We conclude that determining indication for HSCT for CHS patients should be based on genetic and cytotoxic analysis.

Original languageEnglish
Pages (from-to)1582-1586
Number of pages5
JournalPediatric Blood and Cancer
Volume60
Issue number10
DOIs
Publication statusPublished - Oct 1 2013
Externally publishedYes

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Japan
Hemophagocytic Lymphohistiocytosis
Mutation
Hematopoietic Stem Cell Transplantation
Surveys and Questionnaires
Oculocutaneous Albinism
Cytotoxic T-Lymphocytes
Regulator Genes
Bacterial Infections
Lymphoma
Phenotype
Incidence

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Cite this

Clinical characteristics and outcomes of chédiak-Higashi syndrome : A nationwide survey of Japan. / Nagai, Kozo; Ochi, Fumihiro; Terui, Kiminori; Maeda, Miho; Ohga, Shouichi; Kanegane, Hirokazu; Kitoh, Toshiyuki; Kogawa, Kazuhiro; Suzuki, Nobuhiro; Ohta, Shigeru; Ishida, Yasushi; Okamura, Takayuki; Wakiguchi, Hiroshi; Yasukawa, Masaki; Ishii, Eiichi.

In: Pediatric Blood and Cancer, Vol. 60, No. 10, 01.10.2013, p. 1582-1586.

Research output: Contribution to journalArticle

Nagai, K, Ochi, F, Terui, K, Maeda, M, Ohga, S, Kanegane, H, Kitoh, T, Kogawa, K, Suzuki, N, Ohta, S, Ishida, Y, Okamura, T, Wakiguchi, H, Yasukawa, M & Ishii, E 2013, 'Clinical characteristics and outcomes of chédiak-Higashi syndrome: A nationwide survey of Japan', Pediatric Blood and Cancer, vol. 60, no. 10, pp. 1582-1586. https://doi.org/10.1002/pbc.24637
Nagai, Kozo ; Ochi, Fumihiro ; Terui, Kiminori ; Maeda, Miho ; Ohga, Shouichi ; Kanegane, Hirokazu ; Kitoh, Toshiyuki ; Kogawa, Kazuhiro ; Suzuki, Nobuhiro ; Ohta, Shigeru ; Ishida, Yasushi ; Okamura, Takayuki ; Wakiguchi, Hiroshi ; Yasukawa, Masaki ; Ishii, Eiichi. / Clinical characteristics and outcomes of chédiak-Higashi syndrome : A nationwide survey of Japan. In: Pediatric Blood and Cancer. 2013 ; Vol. 60, No. 10. pp. 1582-1586.
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T1 - Clinical characteristics and outcomes of chédiak-Higashi syndrome

T2 - A nationwide survey of Japan

AU - Nagai, Kozo

AU - Ochi, Fumihiro

AU - Terui, Kiminori

AU - Maeda, Miho

AU - Ohga, Shouichi

AU - Kanegane, Hirokazu

AU - Kitoh, Toshiyuki

AU - Kogawa, Kazuhiro

AU - Suzuki, Nobuhiro

AU - Ohta, Shigeru

AU - Ishida, Yasushi

AU - Okamura, Takayuki

AU - Wakiguchi, Hiroshi

AU - Yasukawa, Masaki

AU - Ishii, Eiichi

PY - 2013/10/1

Y1 - 2013/10/1

N2 - Background: Chédiak-Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized by immunodeficiency, neurological dysfunction, and oculocutaneous albinism. Recently, several clinical CHS phenotypes have been reported. Here, we report results of a nationwide survey performed to clarify clinical characteristics and outcomes of CHS patients in Japan. Methods: Questionnaires were sent to 287 institutions to collect data regarding CHS patients diagnosed between 2000 and 2010, including results of lysosomal trafficking regulator (LYST) gene analysis. Cytotoxicity and degranulation activity of cytotoxic T lymphocytes were analyzed in available patient samples. Results: A total of 15 patients diagnosed with CHS were eligible for enrollment in this study. Of these, 10 (67%) had recurrent bacterial infections, five (33%) developed life-threatening hemophagocytic lymphohistiocytosis (HLH), and one patient had complicated malignant lymphoma. Hematopoietic stem cell transplantation (HSCT) was performed for six patients including three with HLH, and 10 of the enrolled patients have survived at the time of this writing. LYST analysis was performed for 10 patients; seven different mutations were detected in seven patients, whereas no mutation was identified in three patients. Cytotoxicity and degranulation activity were impaired in patients with and without LYST mutation. Discussion: Results of this survey indicate that one or two patients with CHS were newly diagnosed each year in Japan. The incidence of HLH was not as high as expected. Mutations of genes other than LYST were suspected in some cases. We conclude that determining indication for HSCT for CHS patients should be based on genetic and cytotoxic analysis.

AB - Background: Chédiak-Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized by immunodeficiency, neurological dysfunction, and oculocutaneous albinism. Recently, several clinical CHS phenotypes have been reported. Here, we report results of a nationwide survey performed to clarify clinical characteristics and outcomes of CHS patients in Japan. Methods: Questionnaires were sent to 287 institutions to collect data regarding CHS patients diagnosed between 2000 and 2010, including results of lysosomal trafficking regulator (LYST) gene analysis. Cytotoxicity and degranulation activity of cytotoxic T lymphocytes were analyzed in available patient samples. Results: A total of 15 patients diagnosed with CHS were eligible for enrollment in this study. Of these, 10 (67%) had recurrent bacterial infections, five (33%) developed life-threatening hemophagocytic lymphohistiocytosis (HLH), and one patient had complicated malignant lymphoma. Hematopoietic stem cell transplantation (HSCT) was performed for six patients including three with HLH, and 10 of the enrolled patients have survived at the time of this writing. LYST analysis was performed for 10 patients; seven different mutations were detected in seven patients, whereas no mutation was identified in three patients. Cytotoxicity and degranulation activity were impaired in patients with and without LYST mutation. Discussion: Results of this survey indicate that one or two patients with CHS were newly diagnosed each year in Japan. The incidence of HLH was not as high as expected. Mutations of genes other than LYST were suspected in some cases. We conclude that determining indication for HSCT for CHS patients should be based on genetic and cytotoxic analysis.

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