Atypical familial hemophagocytic lymphohistiocytosis type 3 in children: A report of cases and literature review

作者全名：Zhao, Qin; Zhao, Qian; Tang, Xuemei; An, Yunfei; Zhang, Zhiyong; Tomomasa, Dan; Hijikata, Atsushi; Yang, Xi; Kanegane, Hirokazu; Zhao, Xiaodong

作者地址：[Zhao, Qin; Zhao, Qian; Tang, Xuemei; An, Yunfei; Zhang, Zhiyong; Yang, Xi; Zhao, Xiaodong] Natl Clin Res Ctr Child Hlth & Disorders, Chongqing Key Lab Child Infect & Immun, Key Lab Child Dev & Disorders, Minist Educ, Chongqing, Peoples R China; [Zhao, Qin] Chongqing Med Univ, Dept Endocrinol, Childrens Hosp, Chongqing, Peoples R China; [Tang, Xuemei; An, Yunfei; Zhang, Zhiyong; Yang, Xi; Zhao, Xiaodong] Chongqing Med Univ, Div Rheumatol & Immunol, Childrens Hosp, Chongqing, Peoples R China; [Tomomasa, Dan] Tokyo Med & Dent Univ TMDU, Grad Sch Med & Dent Sci, Dept Pediat & Dev Biol, Tokyo, Japan; [Hijikata, Atsushi] Tokyo Univ Pharm & Life Sci, Sch Life Sci, Tokyo, Japan; [Kanegane, Hirokazu] Tokyo Med & Dent Univ TMDU, Grad Sch Med & Dent Sci, Dept Child Hlth & Dev, Tokyo, Japan; [Yang, Xi; Zhao, Xiaodong] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Div Rheumatol & Immunol, Minist Edu,Key Lab Child Dev & Disorders,Childrens, Chongqing, Peoples R China

通信作者：Yang, X; Zhao, XD (通讯作者)，Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Div Rheumatol & Immunol, Minist Edu,Key Lab Child Dev & Disorders,Childrens, Chongqing, Peoples R China.

来源：PEDIATRIC ALLERGY AND IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001222889700001

JCR分区：Q1

影响因子：4.3

年份：2024

卷号：35

期号：5

开始页：　

结束页：　

文献类型：Article

关键词：atypical phenotypes; familial hemophagocytic lymphohistiocytosis; UNC13D

摘要：BackgroundFamilial hemophagocytic lymphohistiocytosis type 3 (FHL3) is caused by UNC13D variants. The clinical manifestations of FHL3 are highly diverse and complex. Some patients exhibit atypical or incomplete phenotypes, making accurate diagnosis difficult. Our study aimed to broaden the understanding of the atypical FHL3 clinical spectrum.MethodsIn our study, we analyzed in detail the clinical features of four Chinese patients with UNC13D variants. Additionally, we conducted a comprehensive review of the existing literature on previously reported atypical manifestations and summarized the findings.ResultsTwo of our patients presented with muscle involvement, while the other two had hematological involvement; none of them met the diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH). However, protein expression and functional analysis ultimately confirmed diagnostic criteria for FHL3 in all patients. From the literature we reviewed, many atypical FHL3 patients had neurological involvement, especially isolated neurological manifestations. At the same time, arthritis and hypogammaglobulinemia were also prone to occur.ConclusionOur study highlights that the expression of the Munc13-4 protein may not fully indicate the pathogenicity of UNC13D variants, whereas CD107a analysis could be more sensitive for disease diagnosis. These findings contribute to a broader understanding of the FHL3 clinical spectrum and may offer new insights into the underlying pathogenesis of UNC13D variants. It is crucial to prioritize the timely and accurate diagnosis of atypical patients, as they may often be overlooked among individuals with rheumatic or hematological diseases.

基金机构：Chongqing Postdoctoral Science Foundation Project (CSTB2023NSCQ-BHX0126)

基金资助正文：We thank the patients and their families for participating in this study.