title: Sleep disorders associated with primary mitochondrial diseases.
abstract: OBJECTIVE
  Primary mitochondrial diseases are caused by heritable or spontaneous mutations in nuclear DNA or mitochondrial DNA. Such pathological mutations are relatively common in humans and may lead to neurological and neuromuscular complication that could compromise normal sleep behavior. To gain insight into the potential impact of primary mitochondrial disease and sleep pathology, we reviewed the relevant English language literature in which abnormal sleep was reported in association with a mitochondrial disease.
  
  
  METHODS
  We examined publication reported in Web of Science and PubMed from February 1976 through January 2014, and identified 54 patients with a proven or suspected primary mitochondrial disorder who were evaluated for sleep disturbances.
  
  
  RESULTS
  Both nuclear DNA and mitochondrial DNA mutations were associated with abnormal sleep patterns. Most subjects who underwent polysomnography had central sleep apnea, and only 5 patients had obstructive sleep apnea. Twenty-four patients showed decreased ventilatory drive in response to hypoxia and/ or hyperapnea that was not considered due to weakness of the intrinsic muscles of respiration.
  
  
  CONCLUSIONS
  Sleep pathology may be an underreported complication of primary mitochondrial diseases. The probable underlying mechanism is cellular energy failure causing both central neurological and peripheral neuromuscular degenerative changes that commonly present as central sleep apnea and poor ventilatory response to hyperapnea. Increased recognition of the genetics and clinical manifestations of mitochondrial diseases by sleep researchers and clinicians is important in the evaluation and treatment of all patients with sleep disturbances. Prospective population-based studies are required to determine the true prevalence of mitochondrial energy failure in subjects with sleep disorders, and conversely, of individuals with primary mitochondrial diseases and sleep pathology.
authors.affiliation: Department of Medicine, University of Florida, College of Medicine, Gainesville, FL.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Ramezani
authors.affiliation: Department of Medicine, University of Florida, College of Medicine, Gainesville, FL and Division of Endocrinology, Metabolism and Diabetes, and Department of Biochemistry and Molecular Biology, University of Florida, College of Medicine, Gainesville, FL.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Stacpoole
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D015897:Comorbidity; D005260:Female; D006801:Humans; D006935:Hypercapnia / Q000175:diagnosis / Q000453:epidemiology; D000860:Hypoxia / Q000175:diagnosis / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000175:diagnosis* / Q000453:epidemiology*; D017286:Polysomnography / Q000379:methods; D015995:Prevalence; D011379:Prognosis; D012189:Retrospective Studies; D012720:Severity of Illness Index; D017678:Sex Distribution; D020182:Sleep Apnea, Central / Q000175:diagnosis / Q000453:epidemiology; D020181:Sleep Apnea, Obstructive / Q000175:diagnosis / Q000453:epidemiology; D012893:Sleep Wake Disorders / Q000175:diagnosis* / Q000453:epidemiology*; D055815:Young Adult
keywords: Sleep apnea; congenital lactic acidosis; mitochondrial disease