Case Report: Chronic inflammatory demyelinating polyradiculoneuropathy rather than hemophagocytic lymphohistiocytosis-the initial phenotype of PRF1 gene mutation

Lin-Yan Hu; Lin Wan; Qiu-Hong Wang; Xiu-Yu Shi; Yan Meng; Xiao-Fan Yang; Guang Yang; Li-Ping Zou

doi:10.3389/fimmu.2023.1306338

Case Report: Chronic inflammatory demyelinating polyradiculoneuropathy rather than hemophagocytic lymphohistiocytosis-the initial phenotype of PRF1 gene mutation

Front Immunol. 2023 Dec 11:14:1306338. doi: 10.3389/fimmu.2023.1306338. eCollection 2023.

Authors

Lin-Yan Hu^{1

2}, Lin Wan^{1

2}, Qiu-Hong Wang^{1

2

3}, Xiu-Yu Shi^{1

2}, Yan Meng^{1

2}, Xiao-Fan Yang⁴, Guang Yang^{1

2

3}, Li-Ping Zou^{1

2

3}

Affiliations

¹ Senior Department of Pediatrics, The Seventh Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China.
² Department of Pediatrics, The First Medical Centre, Chinese People's Liberation Army General Hospital, Beijing, China.
³ Graduate School, Medical School of Chinese People's Liberation Army, Beijing, China.
⁴ Department of Pediatrics, Shandong University Qilu Hospital, Jinan, Shandong, China.

Abstract

Perforin is essentially involved in the granule-dependent killing activities of cytotoxic T lymphocytes and NK cells. Monoallelic PRF1 mutation increases the risk of autoimmune diseases, and biallelic PRF1 mutation causes familial hemophagocytic lymphohistiocytosis-2. Here, we report a case of a 12-year-old girl with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), followed by a rapidly progressive onset of hemophagocytic lymphohistiocytosis (HLH) 9 months later, alongside manifestations of demyelinating encephalopathy. Genetic sequencing revealed a heterozygous nonsense mutation in the PRF1 gene (c.984G>A; p.W328*) and a heterozygous missense mutation in the PRF1 gene (c.1349C>T; p.T450M). Eventually, she died because of no suitable allogeneic hematopoietic stem cell available in time. Our observations suggest that CIPD might represent the initial phenotype of biallelic PRF1 mutation and could serve as an early sign of subsequent HLH. A comprehensive understanding of this condition is paramount for timely diagnosis, treatment, and ultimately improved patient outcomes.

Keywords: chronic inflammatory demyelinating polyradiculoneuropathy; demyelination of the central nervous system; familial hemophagocytic lymphohistiocytosis; perforin; perforinopathy.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Child
Female
Humans
Lymphohistiocytosis, Hemophagocytic* / diagnosis
Lymphohistiocytosis, Hemophagocytic* / genetics
Lymphohistiocytosis, Hemophagocytic* / therapy
Mutation, Missense
Perforin / genetics
Phenotype
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating* / diagnosis
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating* / genetics

Substances

Perforin
PRF1 protein, human

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The 14th Five-Year National Key Research and Development Plan (2021YFC2701902); The Capital’s Funds for Health Improvement and Research (2022-1-5081); The National Natural Science Foundation of China (Nos.81071036). All funders had no role in the design and conduct of the study.