Miwa Toru, Hashimoto Kousuke, Seto Toshiyuki, Sakamoto Hirokazu
Department of Otolaryngology, Teikyo University Hospital, Mizonokuchi, Kawasaki, JPN.
Department of Otolaryngology-Head and Neck Surgery, Kyoto University, Kyoto, JPN.
Cureus. 2025 Jun 12;17(6):e85825. doi: 10.7759/cureus.85825. eCollection 2025 Jun.
Mitochondrial diseases can affect multiple organ systems including the auditory pathway, leading to sensorineural hearing loss (SNHL). Although several mitochondrial DNA (mtDNA) mutations are linked to progressive hearing impairment, the underlying mechanisms and clinical course of mitochondrial hearing loss remain incompletely understood. In the present study, we analyzed the frequency and progression of mitochondrial mutations in 15 patients diagnosed with unexplained SNHL who underwent genetic testing at our institution. The most common mutations were m.3243A>G and m.1555A>G. Both are of particular interest due to their relatively high prevalence among mitochondrial mutations and strong clinical implications-m.3243A>G is linked to mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) and diabetes, while m.1555A>G is associated with aminoglycoside-induced and non-syndromic hearing loss. Hearing loss associated with m.3243A>G is generally progressive, although the rate of deterioration varies among individuals. In contrast, the m.1555A>G cases remained stable throughout the follow-up period. No significant correlation was observed between the heteroplasmy levels and hearing deterioration, although a weak negative association was observed. Despite significant hearing impairment, hearing aids are underutilized by a considerable proportion of patients. These findings provide new insights into the phenotypic variability of mitochondrial hearing loss and underscore the need for longitudinal studies to assess its natural progression and potential therapeutic interventions.
线粒体疾病可影响包括听觉通路在内的多个器官系统，导致感音神经性听力损失（SNHL）。尽管几种线粒体DNA（mtDNA）突变与进行性听力损害有关，但线粒体性听力损失的潜在机制和临床过程仍未完全了解。在本研究中，我们分析了15例在我院接受基因检测、被诊断为不明原因SNHL患者的线粒体突变频率和进展情况。最常见的突变是m.3243A>G和m.1555A>G。由于它们在线粒体突变中相对较高的患病率以及强烈的临床意义，这两种突变都特别令人关注——m.3243A>G与线粒体脑肌病、乳酸酸中毒和卒中样发作（MELAS）以及糖尿病有关，而m.1555A>G与氨基糖苷类药物诱发的非综合征性听力损失有关。与m.3243A>G相关的听力损失通常是进行性的，尽管个体之间的恶化速度有所不同。相比之下，m.1555A>G病例在整个随访期间保持稳定。虽然观察到异质性水平与听力恶化之间存在微弱的负相关，但未观察到显著相关性。尽管存在明显的听力障碍，但相当一部分患者未充分使用助听器。这些发现为线粒体性听力损失的表型变异性提供新的见解，并强调需要进行纵向研究以评估其自然进展和潜在的治疗干预措施。
