Long-Term Progression and Rapid Decline in Hearing Loss in Patients with a Point Mutation at Nucleotide 3243 of the Mitochondrial DNA

Abstract

Patients with m.3243A>G mutation of mitochondrial DNA develop bilaterally symmetric sensorineural hearing loss. However, it is unclear how fast their hearing loss progresses over time, and whether they experience rapid progression of hearing loss. In the present study, we conducted a long-term hearing evaluation in patients with MELAS or MIDD who harbored the m.3243A>G mutation of mitochondrial DNA. A retrospective chart review was performed on 15 patients with this mutation who underwent pure-tone audiometry at least once a year for more than two years. The mean follow-up period was 12.8 years. The mean progression rate of hearing loss was 5.5 dB per year. Hearing loss progressed rapidly to be profoundly deaf in seven patients during the observation period. Heteroplasmy and age-corrected heteroplasmy levels correlated with the age of onset of hearing loss. These results indicate that patients with m.3243A>G mutation have a gradual progression of hearing loss in the early stages and rapid decline in hearing to be profoundly deaf in approximately half of the patients. Although it is possible to predict the age of onset of hearing loss from heteroplasmy and age-corrected heteroplasmy levels, it is difficult to predict whether and when the rapid hearing loss will occur.

Hearing and Hearing Loss Progression in Patients with GJB2 Gene Mutations: A Long-Term Follow-Up

“…For homozygous mutations of p.Val37Ile, hearing loss is more likely to progress in patients with severe-moderate hearing loss than in patients with mild hearing loss [32]. In the case of mitochondrial A3243G-related hearing loss, rapid progression may occur after hearing loss has progressed to 55 dB or more [43]. In our study, the three cases with threshold progression initially had moderate hearing loss in one case and severe hearing loss in two cases.…”

The Role of Primary Mitochondrial Disorders in Hearing Impairment: An Overview

“…Where available, the information regarding the degree of hearing loss was analyzed. Only three papers described this aspect of SNHL, which was accordingly stated as mild in 40%, moderate in 34.7%, and severe to profound in 25.3% [ 19 , 20 , 22 ].…”

“…Heteroplasmy plays a crucial role in the pathogenic manifestation of m.3243A>G. According to the literature, the phenotypes linked to m.3243A>G range from asymptomatic to fatal multisystem illnesses. It is observed that subjects with high levels of m.3243A>G mutations manifest a MELAS phenotype, while those with low levels can manifest hearing loss and diabetes [ 18 , 20 ]. Other investigations, though, have shown that hearing loss can develop earlier in patients with higher levels of mutant mitochondrial DNA [ 39 ].…”

Commentary: The mutations and clinical variability in maternally inherited diabetes and deafness: an analysis of 161 patients

“…describe a significant negative correlation between blood heteroplasmy levels and age of onset of diabetes, while a recent study by Sakata et al. found no such correlation, even when correcting for age ( 8 ). Sakata et al.…”

“…Unsurprisingly, attempts to correlate heteroplasmy levels with various clinical metrics, such as age-ofonset of diabetes, have produced conflicting results. For example, Yang et al describe a significant negative correlation between blood heteroplasmy levels and age of onset of diabetes, while a recent study by Sakata et al found no such correlation, even when correcting for age (8). Sakata et al only observed a correlation between heteroplasmy levels and age of onset of hearing loss.…”