Nishinosono Tsubasa, Muramatsu Hideki, Wakamatsu Manabu, Yamashita Daiki, Fukasawa Tatsuya, Shirakawa Yuichi, Sajiki Daichi, Maemura Ryo, Tsumura Yusuke, Yamamori Ayako, Narita Kotaro, Kataoka Shinsuke, Narita Atsushi, Nishio Nobuhiro, Miyajima Yuji, Takahashi Yoshiyuki
Department of Pediatrics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8560, Aichi, Japan.
Department of Pediatrics, Anjo Kosei Hospital, Anjo, Japan.
J Clin Immunol. 2025 Feb 25;45(1):78. doi: 10.1007/s10875-025-01872-4.
B-cell expansion with nuclear factor kappa B and T-cell anergy (BENTA) is an inborn error of immunity characterized by congenital polyclonal B-cell lymphocyte expansion. In this report, we present a case of a girl diagnosed with BENTA carrying a novel CARD11 germline mutation, aiming to clarify the clinical presentation of BENTA by conducting a literature review.
Genetic analysis, including whole-exome sequencing, was performed using genomic DNA extracted from the patient's peripheral blood, oral mucosa, and fingernails. Additionally, a comprehensive literature review of cases with BENTA was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
A p.Leu251Pro germline variant in the CARD11 gene was identified in an 18-month-old girl with a genetic diagnosis of BENTA. She required adenoidectomy and tonsillectomy due to airway obstruction causing wheezing. Her symptoms improved with prednisolone and sirolimus. The literature review we conducted identified a total of 34 cases of BENTA. Among these cases, 15 were either asymptomatic or showed improvement without requiring any specific treatment. However, all six reported deaths were diagnosed before the age of 3 years, with two attributed to refractory hemophagocytic syndrome and four caused by opportunistic infections.
We present a case of BENTA with life-threatening respiratory symptoms caused by a novel CARD11 germline mutation. The patient showed a positive response to immunosuppressive therapy, including sirolimus. While BENTA is typically regarded as a benign disorder, a literature review revealed that infants with BENTA are at high risk of severe outcomes and require therapeutic intervention.
核因子κB介导的B细胞扩增与T细胞无能（BENTA）是一种免疫缺陷病，其特征为先天性多克隆B淋巴细胞扩增。在本报告中，我们介绍了一名被诊断为BENTA的女孩，她携带一种新的CARD11种系突变，旨在通过文献综述阐明BENTA的临床表现。
使用从患者外周血、口腔黏膜和指甲中提取的基因组DNA进行包括全外显子测序在内的基因分析。此外，按照系统评价和Meta分析的首选报告项目指南，对BENTA病例进行了全面的文献综述。
在一名18个月大、基因诊断为BENTA的女孩中，发现了CARD11基因中的一个p.Leu251Pro种系变异。由于气道阻塞导致喘息，她需要进行腺样体切除术和扁桃体切除术。泼尼松龙和西罗莫司使她的症状得到改善。我们进行的文献综述共确定了34例BENTA病例。在这些病例中，15例无症状或症状改善，无需任何特殊治疗。然而，所有6例报告的死亡病例均在3岁前被诊断，其中2例归因于难治性噬血细胞综合征，4例由机会性感染引起。
我们报告了一例由新的CARD11种系突变引起的有生命危险的呼吸道症状的BENTA病例。患者对包括西罗莫司在内的免疫抑制治疗有积极反应。虽然BENTA通常被认为是一种良性疾病，但文献综述显示，患有BENTA的婴儿有严重后果的高风险，需要进行治疗干预。
