title: Prediction of long-term prognosis by heteroplasmy levels of the m.3243A>G mutation in patients with the mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome.
abstract: Our aim was to determine the prognostic value of urine and blood heteroplasmy in patients with the m.3243A>G mutation.
  
  
  
  Adults with the m.3243A>G mutation referred to our institution between January 2000 and May 2014 were retrospectively included. The relationship between their baseline clinical characteristics, their mutation load in urine and blood, and major adverse events (MAEs) during follow-up, defined as medical complications requiring a hospitalization or complicated by death, was studied.
  
  
  
  Of the 43 patients (age 45.6 ± 13.3 years) included in the study, 36 patients were symptomatic, including nine with evidence of focal brain involvement, and seven were asymptomatic. Over a 5.5 ± 4.0 year mean follow-up duration, 14 patients (33%) developed MAEs. Patients with MAEs had a higher mutation load than others in urine (60.1% ± 13.8% vs. 40.6% ± 26.2%, P = 0.01) and in blood (26.9% ± 18.4% vs. 16.0% ± 12.1%, P = 0.03). Optimal cutoff values for the prediction of MAEs were 45% for urine and 35% for blood. In multivariate analysis, mutation load in urine ≥45% [odds ratio 25.3; 95% confidence interval (CI) 1.1-567.8; P = 0.04], left ventricular hypertrophy (odds ratio 16.7; 95% CI 1.3- 222.5; P = 0.03) and seizures (odds ratio 48.3; 95% CI 2.5-933; P = 0.01) were associated with MAEs.
  
  
  
  Patients with the m.3243A>G mutation are at high risk of MAEs, which can be independently predicted by mutation load in urine ≥45%, a personal history of seizures, and left ventricular hypertrophy.
authors.affiliation: AP-HP, Pitié-Salpêtrière Hospital, Reference Centre for Muscle Diseases Paris-Est, Myology Institute, Paris, France.|AP-HP, Raymond Poincaré Hospital, Versailles Saint-Quentin en Yvelines University, Garches, France.
authors.forename: A
authors.initials: A
authors.lastname: Fayssoil
authors.affiliation: AP-HP, Pitié-Salpêtrière Hospital, Reference Centre for Muscle Diseases Paris-Est, Myology Institute, Paris, France.|Myology Institute, Pitié-Salpêtrière Hospital, Pierre et Marie Curie Paris 6 University, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Laforêt
authors.affiliation: INSERM Unit 970, Paris Cardiovascular Research Centre (PARCC), Paris, France.|Paris-Descartes, Sorbonne Paris Cité University, Paris, France.|Medical Intensive Care Unit, AP-HP, Cochin Hospital, Paris, France.
authors.forename: W
authors.initials: W
authors.lastname: Bougouin
authors.affiliation: Biochemistry Department, AP-HP, Pitié-Salpêtrière Hospital, Paris, France.|INSERM U1016, CNRS UMR 8104, Institut Cochin, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Jardel
authors.affiliation: Paris-Descartes, Sorbonne Paris Cité University, Paris, France.|INSERM U1016, CNRS UMR 8104, Institut Cochin, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Lombès
authors.affiliation: AP-HP, Pitié-Salpêtrière Hospital, Reference Centre for Muscle Diseases Paris-Est, Myology Institute, Paris, France.
authors.forename: H M
authors.initials: HM
authors.lastname: Bécane
authors.affiliation: AP-HP, Pitié-Salpêtrière Hospital, Reference Centre for Muscle Diseases Paris-Est, Myology Institute, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Berber
authors.affiliation: AP-HP, Pitié-Salpêtrière Hospital, Reference Centre for Muscle Diseases Paris-Est, Myology Institute, Paris, France.
authors.forename: T
authors.initials: T
authors.lastname: Stojkovic
authors.affiliation: AP-HP, Pitié-Salpêtrière Hospital, Reference Centre for Muscle Diseases Paris-Est, Myology Institute, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Béhin
authors.affiliation: AP-HP, Pitié-Salpêtrière Hospital, Reference Centre for Muscle Diseases Paris-Est, Myology Institute, Paris, France.|Myology Institute, Pitié-Salpêtrière Hospital, Pierre et Marie Curie Paris 6 University, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Eymard
authors.affiliation: AP-HP, Pitié-Salpêtrière Hospital, Reference Centre for Muscle Diseases Paris-Est, Myology Institute, Paris, France.|Paris-Descartes, Sorbonne Paris Cité University, Paris, France.|Department of Cardiology, AP-HP, Cochin Hospital, Paris Descartes University, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Duboc
authors.affiliation: AP-HP, Pitié-Salpêtrière Hospital, Reference Centre for Muscle Diseases Paris-Est, Myology Institute, Paris, France.|Paris-Descartes, Sorbonne Paris Cité University, Paris, France.|Department of Cardiology, AP-HP, Cochin Hospital, Paris Descartes University, Paris, France.
authors.forename: K
authors.initials: K
authors.lastname: Wahbi
mesh_terms: D000328:Adult; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006801:Humans; D017241:MELAS Syndrome / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D012189:Retrospective Studies; D013577:Syndrome
chemical_list: D004272:DNA, Mitochondrial
keywords: death; lactic acidosis and stroke-like episodes; mitochondrial diseases; mitochondrial encephalomyopathy; mutation load; prognosis