Chen Xiaoyi, Gu Hao, Piao Yurong, Ma Yanli, Zhao Yiran, Mao Huawei, Wang Yuan, Deng Jie
Department of Neurology, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China.
Department of Immunology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Front Immunol. 2025 Aug 29;16:1611748. doi: 10.3389/fimmu.2025.1611748. eCollection 2025.
X-linked agammaglobulinemia (XLA) is a rare disorder associated with defective B-lymphocyte differentiation, also known as circulating B-cell deletion or deficiency, reduced levels of all serum immunoglobulin isoforms, and a lack of specific antibody production. XLA has rare neurological complications but has a refractory course and poor prognosis. Here, we report a case of XLA due to a Bruton tyrosine kinase gene variant with progressive neurodegeneration.
We describe a boy with XLA who had recurrent infections since infancy and, after diagnosis was confirmed by genetic testing, was started on regular intravenous immunoglobulin at the age of 5 years. However, after a second episode of suspected meningitis at the age of 4.9 years, he developed motor and cognitive deterioration, becoming unable to sit, walk, eat or speak after 8 months, with frequent tremors and multiple seizures, and died of respiratory failure at the age of 7 years. Magnetic resonance imaging showed progressive whole brain atrophy. Combined with a mild lymphocytic inflammation of the cerebrospinal fluid, we suspected a chronic active infection of the central nervous system, but it was difficult to confirm our suspicion by serological testing due to the inability to produce neutralizing antibodies.
Severe progressive neurodegeneration in XLA is rare. With this case we would like to discuss the difficulties in diagnosing infection in patients with XLA and the role of autoimmune mechanisms in the development of neurodegeneration.
X连锁无丙种球蛋白血症（XLA）是一种罕见的疾病，与B淋巴细胞分化缺陷有关，也称为循环B细胞缺失或缺乏、所有血清免疫球蛋白亚型水平降低以及缺乏特异性抗体产生。XLA有罕见的神经系统并发症，但病程难治且预后不良。在此，我们报告一例因布鲁顿酪氨酸激酶基因突变导致进行性神经退行性变的XLA病例。
我们描述了一名患有XLA的男孩，自婴儿期起就反复感染，在基因检测确诊后，5岁开始定期静脉注射免疫球蛋白。然而，在4.9岁时第二次疑似脑膜炎发作后，他出现了运动和认知功能恶化，8个月后无法坐立、行走、进食或说话，频繁震颤并多次癫痫发作，7岁时死于呼吸衰竭。磁共振成像显示全脑进行性萎缩。结合脑脊液轻度淋巴细胞炎症，我们怀疑中枢神经系统存在慢性活动性感染，但由于无法产生中和抗体，血清学检测难以证实我们的怀疑。
XLA中严重的进行性神经退行性变很罕见。通过这个病例，我们想讨论XLA患者感染诊断的困难以及自身免疫机制在神经退行性变发展中的作用。
