Annals of Hematology

, Volume 98, Issue 10, pp 2303–2310 | Cite as

Genetic characterization of pediatric primary hemophagocytic lymphohistiocytosis in China: a single-center study

  • Liping Zhang
  • Zhigang Li
  • Wei Liu
  • Honghao Ma
  • Tianyou WangEmail author
  • Rui Zhang
Original Article


To study the genetic characteristics of primary hemophagocytic lymphohistiocytosis (pHLH) in China, we investigated the genetic data and clinical features of Chinese HLH patients. We retrospectively reviewed the genetic and clinical data of patients with HLH from November 2015 to June 2018. As a result, 26 patients were diagnosed with pHLH. The median age at diagnosis was 2.8 years (range 0.1–13.7 years). The probable overall survival at 12 and 24 months was 87.6% and 62.6%, respectively. Mutations in PRF1 (38.4%) and UNC13D (26.9%) were the most common genetic abnormalities. Furthermore, we identified 19 novel mutations that had not been previously reported and were predicted to likely be pathogenic. In addition to HLH-associated genes, there were 27 other genes identified. Genotype-phenotype analysis showed that patients with disruptive mutations were significantly younger at diagnosis than those with other mutation types (2.9 years vs. 6.4 years, P = 0.036). Familial HLH patients were more prone to central nervous system involvement and seizures compared with other patients (83.3% vs. 37.5%, P = 0.019; 55.6% vs. 12.5%, P = 0.04, respectively). In summary, numerous new mutations in HLH-related genes and other genes were identified in Chinese children with pHLH. Significantly, disruptive mutation types were more likely to be found in younger patients, and familial HLH patients tended to exhibit central nervous system involvement and seizures.


Primary hemophagocytic lymphohistiocytosis Genotype-phenotype Children Genetics Clinical features China 



We thank all of the patients and their families for their kind cooperation.

Authors’ contributions

Liping Zhang collected clinical the patient data, wrote the paper, and designed and performed the research. Wei Liu and Honghao Ma collected clinical patient data and analyzed the patients. Zhigang Li analyzed the patients, revised the paper, and designed and performed the research. Tianyou Wang and Rui Zhang analyzed the patients, revised the paper, designed and performed the research and contributed patient data. All authors read and approved the final manuscript.


This study was funded by the National Science and Technology Key Projects (No. 2017ZX09304029004), the Beijing Municipal Science & Technology Commission (No. Z171100001017050), the National Natural Science Foundation of China (Nos. 81700186 and 81800189), the Beijing Municipal Administration of Hospitals’ Youth Programme (QML20181205), the Scientific Research Common Program of Beijing Municipal Commission of Education (Nos. KM201710025019 and KM201910025011), the Talent Training Project-Fostering Fund of the National Natural Science Foundation of Beijing Children’s Hospital, Capital Medical University (No. GPY201713), the Special Fund of the Pediatric Medical Coordinated Development Center of the Beijing Hospitals Authority (No. XTZD20180202), and the Guangdong Province Key Laboratory of Popular High-Performance Computers of Shenzhen University (SZU-GDPHPCL2017).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent and ethics approval

Written informed consent was obtained from the parents, and the study was approved by the Beijing Children’s Hospital Ethical Committee.

Supplementary material

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ESM 1 (XLSX 15 kb)
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ESM 2 (XLSX 12 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Hematology and Oncology, Beijing Children’s HospitalCapital Medical UniversityBeijingPeople’s Republic of China
  2. 2.Hematology and Oncology Laboratory, Beijing Pediatric Research Institute, National Center for Children’s Health, Beijing Key Laboratory of Pediatric Hematology Oncology, Key Laboratory of Major Diseases in Children, Ministry of Education, National Key Discipline of PediatricsBeijing Children’s Hospital Affiliated to Capital Medical UniversityBeijingChina
  3. 3.Department of HematologyChildren’s Hospital of Zhengzhou CityZhengzhouChina

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