Objective: To study the progression of hearing impairment (HI) and audiological features in patients with the mitochondrial A to G mutation in the tRNA(LEU(RUU)) gene at position 3,243 associated with maternally inherited diabetes and deafness.
Design: Retrospective phenotype genotype family study.
Setting: Tertiary referral center.
Patients: Six adult family members with the mitochondrial tRNA(LEU(RUU)) gene mutation at location 3,243. Data were obtained on medical history, otological examination, and pure tone and speech audiometry. Peripheral leukocytes were analyzed for the presence of the mutation, and heteroplasmy levels were determined. Selected patients underwent vestibular testing, brainstem-evoked response audiometry and neurological examination.
Results: One patient showed relatively normal hearing, whereas in the others, HI had started at 27 to 79 years of age. All the patients showed progression in HI of approximately 1.4 dB/yr on average at 0.25 and 8 kHz. In the frequency range 0.5 to 2 kHz, progression was approximately 2 dB/yr; at 4 kHz, progression was 2.4 dB/yr. Vestibular and brainstem-evoked response audiometry test results were normal. All the patients achieved the maximum speech recognition score, as was expected based on their pure-tone average at 1, 2, and 4 kHz.
Conclusion: Our six adult patients with the mitochondrial tRNA(LEU(RUU)) gene mutation at location 3,243 showed almost normal to severe HI which was progressive beyond presbyacusis. Data from the literature and our findings suggest a cochlear localization of the HI.