Ding Wenwen, Li Danni, Yu Qi, Wang Yuping, Zhang Lei
Department of Hematology, Qingdao Women and Children's Hospital, Qingdao, China.
Front Immunol. 2025 Aug 20;16:1613433. doi: 10.3389/fimmu.2025.1613433. eCollection 2025.
Familial hemophagocytic lymphohistiocytosis type 2 (FHL2), caused by perforin 1 (PRF 1), is a rare and fatal autosomal recessive disorder characterized by a 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, carrying a new type of compound heterozygous mutations (c.305G>T and c.139G>T) in and a spontaneous heterozygous mutation in the gene (c.776T>C). He met six of the eight hemophagocytic lymphohistiocytosis (HLH) diagnostic criteria: fever, splenomegaly, cytopenia, hypofibrinogenemia, hemophagocytosis in the bone marrow, and elevated sCD25. He also had a high proportion of CD3CD4CD8 T lymphocytes and a spontaneous mutation of , which are features of ALPS. Chemotherapy failed to control the disease, and the child died within 3 months. and comutation may have contributed to the adverse outcome in this patient. Notably, hematopoietic stem cell transplantation (HSCT) should be performed early in these patients.
2型家族性噬血细胞性淋巴组织细胞增生症（FHL2）由穿孔素1（PRF 1）引起，是一种罕见的致命常染色体隐性疾病，其特征为高炎症综合征以及活化的T淋巴细胞和组织细胞在网状内皮系统中蓄积。自身免疫性淋巴增生综合征（ALPS）是一种自身免疫性疾病，通常在儿童中表现为淋巴结病、脾肿大、血细胞减少或淋巴瘤。我们报告了一例9岁男孩，他新诊断为FHL，在 基因中携带一种新型复合杂合突变（c.305G>T和c.139G>T）以及 基因中的一个自发杂合突变（c.776T>C）。他符合八项噬血细胞性淋巴组织细胞增生症（HLH）诊断标准中的六项：发热、脾肿大、血细胞减少、低纤维蛋白原血症、骨髓噬血细胞现象以及sCD25升高。他还具有高比例的CD3CD4CD8 T淋巴细胞以及 的自发突变，这些都是ALPS的特征。化疗未能控制疾病，该患儿在3个月内死亡。 和 共突变可能导致了该患者的不良结局。值得注意的是，这些患者应尽早进行造血干细胞移植（HSCT）。
