Clinical characteristics and hearing impairment in carriers of the m.3243 A > G variant

The m.3243 A > G mitochondrial DNA variant is a major pathogenic variant associated with various clinical phenotypes, including hearing impairment and diabetes. This study retrospectively analyzed clinical data from 37 patients with the m.3243 A > G variant to clarify the relationship between clinical characteristics and hearing loss. Most patients developed post-lingual, late-onset sensorineural hearing loss (SNHL), with flat-type audiometric configurations being the most common. Blood heteroplasmy levels were negatively correlated with age at genetic testing (R² = 0.6303), and age-adjusted heteroplasmy levels were inversely associated with age at onset of hearing loss (p = 0.029). A significant difference in clinical characteristics was observed between patients with hearing loss and/or diabetes alone and those with multiple organ involvement, with the latter group showing a lower BMI (p = 0.031) and more severe hearing loss (p < 0.001). Two cases initially presenting with maternally inherited deafness and diabetes progressed to MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes), demonstrating the importance of early systemic evaluation. Cochlear implantation was considered for advanced hearing loss, although systemic complications were a challenge. Our findings suggest that hearing loss may be an early risk factor of systemic mitochondrial disease, particularly in lean individuals. Comprehensive assessment, including BMI and genetic testing, may aid in the early diagnosis and management of patients with m.3243 A > G variant.