Xue Jiao, Song Zhenfeng, Zhao Hongshan, Yang Chengqing, Li Fei, Yi Zhi, Liu Kaixuan, Zhang Ying
Department of Pediatric Neurology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Department of Anesthesiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Front Genet. 2025 Jul 21;16:1528844. doi: 10.3389/fgene.2025.1528844. eCollection 2025.
Central nervous system-isolated hemophagocytic lymphohistiocytosis (CNS-HLH) is a rare disease caused by mutations in several genes.
Clinical information was obtained from medical records. Genetic analyses were performed using whole-exome sequencing (WES). NK cell function testing, Granzyme B staining, perforin staining, CD107a mobilization, and soluble CD25 levels were determined.
We report the case of a 5-year-old girl who presented with involuntary movements, an unsteady gait, and a progressively irritable temper. Cranial MRI revealed bilateral multifocal white matter abnormalities. The patient harbored a homozygous missense mutation in the gene (NM_001083116.3), c.1349C > T (p.Thr450Met), which is a maternal uniparental disomy. Based on the phenotype and absence of perforin expression, the patient was diagnosed with CNS-HLH.
We report a highly unusual case of CNS-HLH diagnosed by uniparental disomy of a mutation. Exome sequencing should be considered in patients with chronic or recurrent brain inflammation who show partial or no response to conventional treatment regimens.
中枢神经系统孤立性噬血细胞性淋巴组织细胞增生症（CNS-HLH）是一种由多个基因突变引起的罕见疾病。
从病历中获取临床信息。使用全外显子组测序（WES）进行基因分析。测定自然杀伤（NK）细胞功能、颗粒酶B染色、穿孔素染色、CD107a动员及可溶性CD25水平。
我们报告了一名5岁女孩的病例，她出现不自主运动、步态不稳及逐渐易怒的症状。头颅磁共振成像（MRI）显示双侧多灶性白质异常。该患者在 基因（NM_001083116.3）中存在纯合错义突变，c.1349C>T（p.Thr450Met），这是一种母系单亲二倍体。基于表型及穿孔素表达缺失，该患者被诊断为CNS-HLH。
我们报告了一例通过 基因突变单亲二倍体诊断的极为罕见的CNS-HLH病例。对于对传统治疗方案部分或无反应的慢性或复发性脑部炎症患者，应考虑进行外显子组测序。
