CASE REPORT article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1613433
FAS spontaneous mutation in a familial hemophagocytic lymphohistiocytosis patient with a complex heterozygous mutation in PRF1: A case report
Provisionally accepted
- Qingdao Women and Children's Hospital, Qingdao, China
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Familial hemophagocytic lymphohistiocytosis type 2 (FHL2), caused by perforin 1, is a rare and fatal autosomal recessive disorder characterized by hyperinflammatory syndrome and the accumulation of activated T lymphocytes and histiocytes in the reticuloendothelial system. Autoimmune lymphoproliferative syndrome (ALPS) is an autoimmune disease that typically presents in children with lymphadenopathy, splenomegaly, and cytopenias or lymphomas. We report a case of a 9-year-old boy who was newly diagnosed with FHL carried a new type of compound heterozygous mutations (c.305G>T and c.139G>T) in PRF1 and a spontaneous heterozygous mutation in the FAS gene (c.776T>C). He met 6 of 8 hemophagocytic Lymphohistiocytosis (HLH) diagnostic criteria: fever, splenomegaly, cytopenia, hypofibrinogenemia, hemophagocytosis in the bone marrow, and elevated sCD25. He also had a high proportion of CD3 + CD4 -CD8 -T lymphocytes and spontaneous mutation of FAS, which are features of autoimmune lymphoproliferative syndrome (ALPS). Chemotherapy failed to control the disease, and the child died within three months. FAS and PRF1 comutation may have contributed to the adverse outcome of this patient. Notably, hematopoietic stem cell transplantation (HSCT) should be performed early in these patients.
Keywords: FAS mutation, PRF1 mutation, Autoimmune Lymphoproliferative Syndrome, hemophagocytic lymphohistiocytosis, comutation
Received: 17 Apr 2025; Accepted: 21 Jul 2025.
Copyright: © 2025 Ding, Li, Yu, Wang and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Wenwen Ding, Qingdao Women and Children's Hospital, Qingdao, China
Lei Zhang, Qingdao Women and Children's Hospital, Qingdao, China
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