Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital; Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.
Department of Otolaryngological, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Rheumatology (Oxford). 2024 May 3;63(6):1690-1698. doi: 10.1093/rheumatology/kead451.
Nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3-associated autoinflammatory disease (NLRP3-AID) is a rare autosomal dominant systemic autoinflammatory disease. We aimed to summarize the phenotypic and genotypic features of Chinese adult NLRP3-AID patients with hearing loss.
A retrospective cohort study of twenty-one adult patients with NLRP3-AID was conducted in Peking Union Medical College Hospital between July 2015 and March 2023. All patients underwent whole exome sequencing and otorhinolaryngologic assessments. Clinical features and therapeutic data were collected and analysed.
We found that 13/21 (61.90%) of patients had hearing loss with high-frequency impairment in the majority, and most patients presented with vestibular dysfunction as a new finding. The NLRP3-AID patients with early-onset, cold or stress triggered episodes, red eyes, fatigue, hypopsia and mutations located in the NACHT domain of the NLRP3 protein were more likely to suffer from hearing loss, especially sensorineural hearing loss, perhaps as a result of pathogenic variants of high penetrance. By a series of audiological evaluations, TNF-α inhibitors were confirmed to improve or reverse hearing loss.
We reported the first cohort of Chinese adult NLRP3-AID patients with hearing loss and characterized vestibular dysfunction, highlighted the necessity for attention to high-frequency hearing and provided potential alternative treatment.
核苷酸结合寡聚化结构域样受体家族，富含吡咯结构域的 3 蛋白相关自身炎症性疾病（NLRP3-AID）是一种罕见的常染色体显性遗传系统性自身炎症性疾病。我们旨在总结伴有听力损失的中国成年 NLRP3-AID 患者的表型和基因型特征。
对 2015 年 7 月至 2023 年 3 月期间在北京协和医院就诊的 21 例 NLRP3-AID 成年患者进行了回顾性队列研究。所有患者均进行了全外显子组测序和耳鼻喉科评估。收集并分析了临床特征和治疗数据。
我们发现 13/21（61.90%）例患者有听力损失，多数为高频听力损失，大多数患者表现为前庭功能障碍，这是新发现。具有早发、冷或应激触发发作、红眼、疲劳、视力下降和 NLRP3 蛋白 NACHT 结构域突变的 NLRP3-AID 患者更有可能发生听力损失，特别是感觉神经性听力损失，这可能是由于高外显率的致病性变异。通过一系列听力学评估，TNF-α 抑制剂被证实可改善或逆转听力损失。
我们报告了中国首例伴有听力损失的成年 NLRP3-AID 患者队列，并描述了前庭功能障碍，强调了对高频听力的重视，并提供了潜在的替代治疗方法。
