Case Report
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jul 26, 2021; 9(21): 6056-6066
Published online Jul 26, 2021. doi: 10.12998/wjcc.v9.i21.6056
Familial hemophagocytic lymphohistiocytosis type 2 in a female Chinese neonate: A case report and review of the literature
Shao-Hua Bi, Liang-Liang Jiang, Li-Ying Dai, Li-Li Wang, Guang-Hui Liu, Ru-Jeng Teng
Shao-Hua Bi, Li-Li Wang, Division of Neonatology, Department of Pediatrics, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China
Shao-Hua Bi, Li-Ying Dai, Guang-Hui Liu, Department of Neonatology, Anhui Provincial Children's Hospital, Hefei 230022, Anhui Province, China
Liang-Liang Jiang, Department of Pediatric Neurology, Anhui Provincial Children's Hospital, Hefei 230022, Anhui Province, China
Ru-Jeng Teng, Department of Pediatrics, Medical College of Wisconsin, Wauwatosa, WI 53226, United States
Author contributions: Bi SH and Dai LY contributed to conceptualization; Bi SH and Jiang LL contributed to the data curation; Bi SH and Liu GH contributed to the investigation; Bi SH wrote the original draft; Bi SH, Wang LL, and Teng RJ reviewed and edited the manuscript.
Informed consent statement: Informed written consent was obtained from the patient’s parents for publication of this report and any accompanying images.
Conflict-of-interest statement: All authors declare no conflict of interest for this manuscript.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Li-Li Wang, MD, Chief Doctor, Division of Neonatology, Department of Pediatrics, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Shushan District, Hefei 230022, Anhui Province, China.
Received: March 14, 2021
Peer-review started: March 14, 2021
First decision: March 27, 2021
Revised: April 6, 2021
Accepted: May 15, 2021
Article in press: May 15, 2021
Published online: July 26, 2021

Familial hemophagocytic lymphohistiocytosis type 2 (FHL2) is a rare genetic disorder presenting with fever, hepatosplenomegaly, and pancytopenia secondary to perforin-1 (PRF1) mutation. FLH2 has been described in Chinese but usually presents after 1 year old. We describe a female Chinese neonate with FHL2 secondary to compound heterozygous PRF1 mutation with symptom onset before 1 mo old. We review Chinese FHL2 patients in the literature for comparison.


A 15-d-old female neonate was referred to our hospital for persistent fever and thrombocytopenia with diffuse petechiae. She was born to a G5P3 mother at 39 wk and 4 d via cesarean section secondary to breech presentation. No resuscitation was required at birth. She was described to be very sleepy with poor appetite since birth. She developed a fever up to 39.5°C at 7 d of life. Leukocytosis, anemia, and thrombocytopenia were detected at a local medical facility


A literature review identified 75 Chinese FHL2 patients, with only five presenting in the first year of life. Missense and frameshift mutations are the most common PRF1 mutations in Chinese, with 24.8% having c.1349C>T followed by 11.6% having c.65delC. The c.658G>C mutation has only been reported once in the literature and our case suggests it can be pathogenic, at least in the presence of another pathogenic mutation such as c.1066C>T.

Keywords: Hemophagocytic lymphohistiocytosis, Familial hemophagocytic lymphohistiocytosis, Perforin-1, Neonate, Compound heterozygous, Case report

Core Tip: We report the case of a newborn infant with familial hemophagocytic lymphohistiocytosis who had clinical manifestations by the age of 7 d. The genetic test revealed a compound heterozygous mutation of c.658G>C (p.Gly220Arg) and c.1066C>T (p.Arg356Trp). The two mutations carried by the index cases were not commonly seen variants in Chinese PRF1 mutations. The clinical manifestation of our case strongly suggests that c.658G>C (p.Gly220Arg) is also a pathogenic variant.