EARLY-ONSET SENSORINEURAL HEARING-LOSS AND LATE-ONSET NEUROLOGIC COMPLAINTS CAUSED BY A MITOCHONDRIAL MUTATION AT POSITION-74-72

Objectives: To detect a mitochondrial mutation responsible for materna lly transmitted hearing loss with late-onset neurologic features in a 3-generation Dutch family, and to describe the hearing loss, associate d symptoms, and vestibular dysfunction. Patients and Methods: All mate rnally related family members (n = 69) were investigated using standar d audiometry. In a selected group, vestibule-ocular examinations and a dditional neurologic and ophthalmologic examinations were performed. T wenty milliliters of venous blood was taken from all participants for genetic studies. Setting: University medical center. Results: All mate rnally related individuals carried an extra C at position 7472 of the mitochondrial genome. Hearing loss was the only symptom or presenting symptom in most family members and most pronounced at higher frequenci es. Hearing loss at lower frequencies was demonstrated in individuals 10 years and older. Most patients had vestibular hyperreactivity and w ere susceptible to motion sickness, suggesting vestibulocerebellar dys function. Neurologic complaints were infrequent and presented by older individuals; however, numerous enlarged mitochondria were found in a muscle biopsy specimen of an individual with hearing impairment but wi thout neurologic symptoms. Conclusions: Respiratory chain dysfunction should be considered as a possible cause of progressive sensorineural hearing loss. More research into the causes of high-frequency impairme nt should be considered; especially when sensorineural hearing loss, s yndromal or nonsyndromal, is exclusively maternally transmitted. Mater nal transmission of hearing impairment can also be valuable in the dia gnosis of unclear neurologic syndromes.