title: Mitochondrial Encephalopathy and Optic Neuropathy Due to m.10158 MT-ND3 Complex I Mutation Presenting in an Adult Patient: Case Report and Review of the Literature.
abstract: BACKGROUND
  Establishing a diagnosis of mitochondrial disease in adults remains a clinician's challenge. We report a case of syndrome reminiscent of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) in an adult patient who carries m.10158T>C mutation in complex I respiratory chain gene MT-ND3 (mitochondrially encoded NADH dehydrogenase 3).
  
  
  METHODS
  This 26-year-old man from Thailand presented with new-onset headaches, seizures, stroke-like episodes, and poor vision due to optic neuropathy and cortical blindness. Instead of expected mutations in the mitochondrial tRNA gene that are frequently associated with MELAS, the mutation in MT-ND3 with variable tissue heteroplasmy (blood 5.3%, muscle 89.5%) was demonstrated. The patient's clinical features, blood biomarkers, neuroimaging findings, muscle biopsy with histochemical and functional in vitro analysis, and genetic studies were analyzed and compared with all previously reported ND3 disease cases.
  
  
  CONCLUSIONS
  ND3 disease due to m.10158T>C mutation was previously described only in patients with Leigh or Leigh-like syndrome. Our findings thus indicate that ND3 disease can manifest with atypical phenotype in adults. The diagnosis of mitochondrial disease caused by other than typical MELAS-associated mutations in adults with stroke-like episodes, headaches, and seizures should be considered. An analysis of tissue other than blood, which is more likely to harbor a tissue-specific mitochondrial DNA mutation at a measurable level, may be necessary for diagnosis.
authors.affiliation: *Harvard Medical School †Department of Neurology, Massachusetts General Hospital ‡Massachusetts Eye and Ear Infirmary, Neuro-Ophthalmology Service §Massachusetts General Hospital, Neuropathology Service, Boston, MA.
authors.forename: Ivana
authors.initials: I
authors.lastname: Vodopivec
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Cho
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Rizzo
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Frosch
authors.forename: Katherine B
authors.initials: KB
authors.lastname: Sims
mesh_terms: D000328:Adult; D042967:Electron Transport Complex I / Q000235:genetics*; D006801:Humans; D017241:MELAS Syndrome / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics; D009901:Optic Nerve Diseases / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D042967:Electron Transport Complex I; C114961:MT-ND3 protein, human