PP1005 - Audiological Characteristics in Primary Mitochondrial Diseases: Genotype-Specific Impacts and Clinical Implications

Abstract:
This study investigates genotype-specific auditory dysfunction in Primary Mitochondrial Diseases (PMD). Seventy-two adults with PMD underwent comprehensive audiological assessments, including Pure-Tone Audiometry, Quick Speech-in-Noise Test, and Auditory Brainstem Responses. Results revealed that patients with m.3243A >G/T variants exhibited significant cochlear and central auditory pathway involvement, with elevated hearing thresholds and spatial processing deficits. These findings emphasize the need for personalized auditory assessments and targeted rehabilitation strategies that address both cochlear and neural impairments, as traditional hearing aids and cochlear implants may not adequately manage the complex auditory dysfunctions seen in PMD.

Summary
Rationale/

Purpose:
Primary Mitochondrial Diseases (PMD) represent a group of genetic disorders that disrupt mitochondrial function, affecting organs with high energy demands, including the auditory system. Individuals with PMD often experience hearing impairments, yet the relationship between specific genetic mutations and auditory dysfunction remains under-researched. The purpose of this study is to investigate genotype-specific impacts on auditory dysfunction in PMD patients and to provide insights into the clinical implications for personalized diagnosis and management. We hypothesize that different mitochondrial mutations, particularly the m.3243A >G/T variants, result in distinct auditory profiles.

Methods:
Seventy-two adults diagnosed with PMD participated in the study. Comprehensive audiological assessments were conducted, including Pure-Tone Audiometry (PTA) to evaluate hearing thresholds, Quick Speech-in-Noise Test (QSiN) for assessing speech perception in noise, Listening in Spatialized Noise-Sentences test (LiSN-S) for spatial processing abilities, and Auditory Brainstem Responses (ABR) to examine neural/central auditory pathways. Statistical analyses, including Multivariate Analysis of Covariance (MANCOVA) and logistic regression, were employed to explore the effects of mitochondrial DNA mutations, particularly the m.3243A >G/T variants, on auditory function. Audiological data were analyzed to identify genotype-phenotype correlations and to determine whether specific mutations predispose patients to more severe or complex auditory dysfunctions.

Results:
The study found that patients with m.3243A >G/T variants demonstrated significantly elevated PTA thresholds, particularly at high frequencies, indicating cochlear involvement. QSiN and LiSN-S results showed that these patients also had substantial spatial processing deficits, suggesting additional central auditory processing impairments. ABR findings further supported the involvement of neural/central auditory pathways. The data revealed a clear genotype-phenotype correlation, with certain mitochondrial variants predisposing individuals to more severe auditory dysfunction.

Conclusions:
Our study emphasizes personalized auditory assessments and management strategies for patients with PMD. The heterogeneous nature of hearing impairments in this population, driven by specific mitochondrial mutations, suggests that a one-size-fits-all approach to rehabilitation is insufficient. Innovative strategies that target both cochlear and central auditory pathways are urgently required to improve outcomes for these patients. Future research should explore novel auditory rehabilitation technologies that cater to the unique needs of individuals with mitochondrial-related hearing loss.

Instructional Level:
This presentation is designed for an advanced audience, particularly audiologists and clinicians with a background in genetics or neuro-audiology. The instructional level assumes familiarity with audiological assessment techniques and an understanding of the genetic underpinnings of hearing disorders. The session will provide detailed insights into the clinical implications of genotype-specific auditory dysfunction, emphasizing the importance of integrating genetic knowledge into audiological practice.

Innovation:
This study introduces an innovative approach to audiological assessment in PMD by correlating specific mitochondrial mutations with distinct auditory profiles. The use of advanced audiological testing, such as LiSN-S and ABR, combined with genetic data, offers a novel perspective on the diagnosis and management of hearing impairments in PMD. These findings contribute to the growing field of personalized medicine, demonstrating the importance of tailoring clinical interventions to the genetic profiles of patients.