A 3-year-old girl presented with severe epilepsy in the context of Borrelia infection. After ceftriaxone/lidocaine administration, she showed secondarily generalized focal crises that led to neurological and motor sequelae. Genetic studies identified in the patient two heterozygous POLG mutations (c.2591A>G; p.Asn864Ser and c.3649G>C; p.Ala1217Pro). Through analysis of POLG activity in cultured fibroblasts, we confirmed that the mutations altered the mtDNA turnover. Moreover, patient fibroblasts were more sensitive than controls in the presence of a mitochondrial replication-affecting drug, the antiretroviral azidothymidine. To test if ceftriaxone treatment could worsen the deleterious effect of the patient mutations, toxicity assays were performed. Cell toxicity, without direct effect on mitochondrial respiratory function, was detected at different antibiotic concentrations. The clinical outcome, together with the different in vitro sensitivity to ceftriaxone among patient and control cells, suggested that the mitochondrial disease symptoms were hastened by the infection and were possibly worsened by the pharmacological treatment. This study underscores the benefit of early genetic diagnosis of the patients with mitochondrial diseases, since they may be a target group of patients especially vulnerable to environmental factors.

中文翻译：

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传染性应激会引发与POLG相关的线粒体疾病。

一名3岁女孩在感染疏螺旋体后出现严重的癫痫病。在服用头孢曲松/利多卡因后，她表现出继发的广泛性局灶性危机，导致了神经系统疾病和运动性后遗症。遗传学研究确定了患者中的两种杂合POLG突变（c.2591A> G; p.Asn864Ser和c.3649G> C; p.Ala1217Pro）。通过分析培养的成纤维细胞中的POLG活性，我们证实了该突变改变了mtDNA转换。此外，在存在线粒体复制影响药物抗逆转录病毒叠氮胸苷的情况下，患者成纤维细胞比对照组更敏感。为了测试头孢曲松治疗是否可以恶化患者突变的有害作用，进行了毒性试验。在不同的抗生素浓度下检测到细胞毒性，而对线粒体呼吸功能没有直接影响。临床结果以及患者和对照细胞对头孢曲松的体外敏感性不同，提示线粒体疾病的症状会因感染而加快，并可能通过药物治疗而恶化。这项研究强调了线粒体疾病患者早期遗传学诊断的益处，因为他们可能是目标人群，尤其是易受环境因素影响的患者。