title: Natural history of MELAS associated with mitochondrial DNA m.3243A>G genotype.
abstract: OBJECTIVE
  To describe the natural history of clinical and laboratory features associated with the m.3243A>G mitochondrial DNA point mutation. Natural history data are needed to obtain prognostic information and for clinical trial planning.
  
  
  METHODS
  We included 85 matrilineal relatives from 35 families with at least 2 visits in this prospective cohort study. Thirty-one were fully symptomatic with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), and 54 were carrier relatives. Evaluations included standardized questionnaires (medical history and daily living functioning), physical examination, neuropsychological testing, and a battery of imaging and laboratory tests. We evaluated changes in clinical and laboratory features over time and survival. Outcomes are reported over a follow-up period of up to 10.6 years (mean 3.8 ± 2.2 years for patients and 5.5 ± 3.0 for carrier relatives).
  
  
  RESULTS
  Neurologic examination, neuropsychological testing, and daily living scores significantly declined in all patients with MELAS, whereas no significant deterioration occurred in carrier relatives. Cerebral MRI scores declined significantly in patients with MELAS. Magnetic resonance spectroscopy estimates of lactate in the lateral ventricles increased over time, and high lactate was associated with increased mortality. Symptom onset in childhood often was associated with worse outcome. Patients with MELAS had a greater death rate than carrier relatives.
  
  
  CONCLUSIONS
  Patients with MELAS carrying the m.3243A>G mutation show a measurable decline in clinical and imaging outcomes. It is hoped that these data will be helpful in anticipating the disease course and in planning clinical trials for MELAS.
authors.affiliation: The Neurological Institute, Columbia University, 710 W. 168th Street, New York, NY 10032, USA. pk88@columbia.edu
authors.forename: P
authors.initials: P
authors.lastname: Kaufmann
authors.forename: K
authors.initials: K
authors.lastname: Engelstad
authors.forename: Y
authors.initials: Y
authors.lastname: Wei
authors.forename: R
authors.initials: R
authors.lastname: Kulikova
authors.forename: M
authors.initials: M
authors.lastname: Oskoui
authors.forename: D M
authors.initials: DM
authors.lastname: Sproule
authors.forename: V
authors.initials: V
authors.lastname: Battista
authors.forename: D Y
authors.initials: DY
authors.lastname: Koenigsberger
authors.forename: J M
authors.initials: JM
authors.lastname: Pascual
authors.forename: S
authors.initials: S
authors.lastname: Shanske
authors.forename: M
authors.initials: M
authors.lastname: Sano
authors.forename: X
authors.initials: X
authors.lastname: Mao
authors.forename: M
authors.initials: M
authors.lastname: Hirano
authors.forename: D C
authors.initials: DC
authors.lastname: Shungu
authors.forename: S
authors.initials: S
authors.lastname: Dimauro
authors.forename: D C
authors.initials: DC
authors.lastname: De Vivo
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D017241:MELAS Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D017354:Point Mutation / Q000235:genetics*; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial
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