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

Abstract

Background. Defects of mitochondrial DNA (mtDNA) involved in the function of the mitochondrial electron transport chain can result in primary mitochondrial diseases (PMDs). Various features can influence the phenotypes of different PMDs, with relevant consequences on clinical presentation, including the presence of hearing impairment. This paper aims to describe the hearing loss related to different PMDs, and when possible, their phenotype. Methods. A systematic review was performed according to PRISMA guidelines, searching Medline until December 2022. A total of 485 papers were identified, and based on specified criteria, 7 were included in this study. Results. A total of 759 patients affected by PMDs and hearing loss were included. The age of patients ranged from 2 days to 78 years old, and the male-to-female ratio was 1.3:1. The percentage of subjects affected by hearing loss was 40.8%, (310/759), and in most cases, hearing impairment was described as sensorineural, bilateral, symmetrical, and progressive, with different presentations depending on age and syndrome severity. Conclusions. PMDs are challenging conditions with different clinical phenotypes. Hearing loss, especially when bilateral and progressive, may represent a red flag; its association with other systemic disorders (particularly neuromuscular, ocular, and endocrine) should alert clinicians, and confirmation via genetic testing is mandatory nowadays.

Hereditary spastic paraparesis type 46 (SPG46): new GBA2 variants in a large Italian case series and review of the literature

“…Six cases of hearing loss have been reported. This is a symptom frequently found in mitochondrial diseases [ 51 , 52 ]. Since a role in mitochondrial fragmentation has been already outlined in GBA2 mutation [ 53 ], we may suppose a similar mechanism in SPG46.…”

Hearing Impairment and Neuroimaging Results in Mitochondrial Diseases

“…In MDs, hearing impairment may be non-syndromic, as deafness is an isolated symptom, or associated with other disorders in syndromic hearing loss. Syndromic hearing loss includes Mitochondrial Encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS); maternally inherited diabetes with deafness (MIDD); chronic progressive external ophthalmoplegia (CPEO); and Myoclonic Epilepsy with Ragged-Red Fibers (MERRF) [ 2 , 3 ].…”

Letter to the Editor: Depending on the Disease Stage and Modifying Factors, mtDNA-Associated Hearing Loss Can Occur With Many mtDNA Mutations

“…Sixth, pre- and postlingual HL is particularly associated with the variants m.1555A>G and m.7444G>A, but can generally be found in any of the mtDNA mutations. 2 Depending on the disease stage and modifying factors that influence the phenotypic expression of an mtDNA, variant, in principle, all syndromic and non-syndromic MIDs can be associated with HL.…”