title: Progressive sensorineural hearing impairment in maternally inherited diabetes mellitus and deafness (MIDD).
abstract: 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.
  
  
  METHODS
  Retrospective phenotype genotype family study.
  
  
  METHODS
  Tertiary referral center.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Otorhinolaryngology, University Medical Centre, St. Radboud, Nijmegen, the Netherlands.
authors.forename: Jan-Jaap
authors.initials: JJ
authors.lastname: Hendrickx
authors.forename: Aart H
authors.initials: AH
authors.lastname: Mudde
authors.forename: Leen M
authors.initials: LM
authors.lastname: 't Hart
authors.forename: Patrick L M
authors.initials: PL
authors.lastname: Huygen
authors.forename: Cor W R J
authors.initials: CW
authors.lastname: Cremers
mesh_terms: D000328:Adult; D000368:Aged; D001300:Audiometry, Evoked Response; D001301:Audiometry, Pure-Tone; D004272:DNA, Mitochondrial / Q000235:genetics*; D003638:Deafness / Q000150:complications / Q000235:genetics*; D003920:Diabetes Mellitus / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006319:Hearing Loss, Sensorineural / Q000209:etiology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017354:Point Mutation; D012356:RNA, Transfer, Leu / Q000235:genetics*; D012044:Regression Analysis; D012189:Retrospective Studies; D012737:Sex Factors
chemical_list: D004272:DNA, Mitochondrial; D012356:RNA, Transfer, Leu