The Otolaryngological Manifestations of Mitochondrial Disease and the Risk of Neurodegeneration With Infection | Infectious Diseases | JAMA Otolaryngology–Head & Neck Surgery | JAMA Network
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Naviaux  RKMcGowan  KA Organismal effects of mitochondrial dysfunction.  Hum Reprod.2000;15(suppl 2):44-56.Google Scholar
Naviaux  RK Mitochondrial DNA disorders.  Eur J Pediatr.2000;159(suppl):S219-S226.Google Scholar
Naviaux  RK The mitochondrial DNA depletion syndromes.  In: Nyhan  WL, Ozand  PT, eds.  Atlas of Metabolic Disease. New York, NY: Chapman & Hall; 1999:314-320. Google Scholar
DiMauro  SBonilla  E Mitochondrial encephalomyelopathies.  In: Rosenberg  RN, Pruisner  SB, DiMauro  S, Barchi  RL, eds.  The Molecular and Genetic Basis of Neurological Disease.2nd ed. Woburn, Mass: Butterworth-Heinemann; 1997:201-235. Google Scholar
Kerr  DS Protean manifestations of mitochondrial diseases: a minireview.  J Pediatr Hematol Oncol.1997;19:279-286.Google Scholar
Munnich  ARötig  AChretien  DSaudubray  JMCormier  VRustin  P Clinical presentations and laboratory investigations in respiratory chain deficiency.  Eur J Pediatr.1996;155:262-274.Google Scholar
Willems  PJ Genetic causes of hearing loss.  N Engl J Med.2000;342:1101-1109.Google Scholar
Fischel-Ghodsian  N Mitochondrial genetics and hearing loss: the missing link between genotype and phenotype.  Proc Soc Exp Biol Med.1998;218:1-6.Google Scholar
Jacobs  HT Mitochondrial deafness.  Ann Med.1997;29:483-491.Google Scholar
Gorga  MPKaminski  JRBeauchaine  KLJesteadt  WNeely  ST Auditory brainstem response from children three months to three years of age: normal patterns of response II.  J Speech Hear Res.1989;32:281-288.Google Scholar
Fox  JPHall  CECooney  MKLuce  REKronmal  RA The Seattle Virus Watch, II: objectives, study, population and observation, data processing, and summary of illnesses.  Am J Epidemiol.1972;96:270-285.Google Scholar
Partin  JC Reye's syndrome.  In: Suchy  F, ed.  Liver Disease in Children. St Louis, Mo: Mosby–Year Book; 1994:653-671. Google Scholar
Usami  SAbe  SKasai  M  et al Genetic and clinical features of sensorineural hearing loss associated with the 1555 mitochondrial mutation.  Laryngoscope.1997;107:483-490.Google Scholar
Braverman  IJaber  LAdelman  C  et al Audiovestibular findings in patients with deafness caused by a mitochondrial susceptibility mutation and precipitated by an inherited nuclear mutation or aminoglycosides.  Arch Otolaryngol Head Neck Surg.1996;122:1001-1004.Google Scholar
Sue  CMLipsett  LJCrimmins  DS  et al Cochlear origin of hearing loss in MELAS syndrome.  Ann Neurol.1998;43:350-359.Google Scholar
Nakamura  YTakahashi  MKitaguchi  M Abnormal evoked potentials of Kearns-Sayre syndrome.  Electromyogr Clin Neurophysiol.1995;35:365-370.Google Scholar
Araki  SHayashi  MYasaka  K  et al Electrophysiological brainstem dysfunction in a child with Leigh disease.  Pediatr Neurol.1997;16:329-333.Google Scholar
Kaga  MNaitoh  HNihei  K Auditory brainstem response in Leigh's syndrome.  Acta Paediatr Jpn.1987;29:254-260.Google Scholar
Taylor  MRobinson  B Evoked potentials in children with oxidative metabolic defects leading to Leigh syndrome.  Pediatr Neurol.1992;8:25-29.Google Scholar
Fischel-Ghodsian  N Mitochondrial genetics and hearing loss: the missing link between genotype and phenotype.  Proc Soc Exp Biol Med.1998;218:1-6.Google Scholar
Hutchin  TPCortopassi  GA Mitochondrial defects and hearing loss.  Cell Mol Life Sci.2000;57:1927-1937.Google Scholar
Gold  MRapin  I Non-mendelian mitochondrial inheritance as a cause of progressive genetic sensorineural hearing loss.  Int J Pediatr Otorhinolaryngol.1994;30:91-104.Google Scholar
Cohen  BHShoffner  JDeBoer  G Anesthesia and mitochondrial cytopathies.  United Mitochondrial Disease Foundation: Mitochondrial News.1998;3(1):1-4.Google Scholar
Original Article
April 2002

The Otolaryngological Manifestations of Mitochondrial Disease and the Risk of Neurodegeneration With Infection

Author Affiliations

From the Departments of Otolaryngology, Children's Hospital, San Diego, Calif (Drs Edmonds and Kearns); University of Kansas Medical Center, Kansas City (Dr Kirse); and the Departments of Family and Preventive Medicine (Dr Deutsch), Pediatrics (Dr Spruijt), and Medicine (Dr Naviaux), University of California–San Diego. Dr Edmonds is now with the Department of Otolaryngology, Texas Children's Hospital, Houston; Dr Spruijt is now with the Department of Clinical Genetics, Academic Hospital, Maastricht, the Netherlands.

Arch Otolaryngol Head Neck Surg. 2002;128(4):355-362. doi:10.1001/archotol.128.4.355

Objective  To report the nature and extent of hearing loss and other otolaryngological problems in patients with mitochondrial disease, and to document the risk of neurodegeneration with infection.

Design  Medical chart review and telephone interview of 40 patients with documented mitochondrial disease.

Setting  An international referral center for the diagnosis and management of mitochondrial disorders.

Patients  We describe 40 patients with a definitive diagnosis of mitochondrial disease. Thirty-three (82%) were younger than 15 years.

Results  Hearing loss was the most common clinical finding associated with mitochondrial disease. Twenty-eight (80%) of the 35 patients undergoing testing had hearing loss or significant auditory dysfunction. In 20 (57%) of these, brainstem conduction abnormalities were identified. Eight (30%) of the 27 patients had an abnormal number of recurrent upper respiratory tract infections, and 4 (50%) of these had life-threatening or neurodegenerative sequelae. Mitochondrial disease followed an episodic course, with periods of stasis or slow developmental progress, punctuated by neurodegenerative events in 18 (60%) of 30 patients. Intercurrent infection was recognized as a precipitant of neurodegenerative events in 13 (72%) of 18 patients with a history of episodic degeneration.

Conclusions  Children and adults with mitochondrial disorders are at high risk for hearing loss and life-threatening complications of intercurrent infections. A constellation of audiologic abnormalities, multiorgan system involvement, and history of neuromuscular setbacks with infection strongly suggests mitochondrial disease. Knowledge of these features can lead to more rapid diagnosis and improved medical and surgical management for this special group of patients with fundamental defects in bioenergy metabolism.