Mitochondrial disorders and epilepsy

Rev Neurol (Paris). 2014 May;170(5):375-80. doi: 10.1016/j.neurol.2014.03.010. Epub 2014 May 5.


Introduction: Mitochondrial respiratory chain defects (RCD) often exhibit multiorgan involvement, affecting mainly tissues with high-energy requirements such as the brain. Epilepsy is frequent during the evolution of mitochondrial disorders (30%) with different presentation in childhood and adulthood in term of type of epilepsy, of efficacy of treatment and also in term of prognosis.

State of art: Mitochondrial disorders can begin at any age but the diseases with early onset during childhood have generally severe or fatal outcome in few years. Four age-related epileptic phenotypes could be identified in infancy: infantile spasms, refractory or recurrent status epilepticus, epilepsia partialis continua and myoclonic epilepsy. Except for infantile spasms, epilepsy is difficult to control in most cases (95%). In pediatric patients, mitochondrial epilepsy is more frequent due to mutations in nDNA-located than mtDNA-located genes and vice versa in adults. Ketogenic diet could be an interesting alternative treatment in case of recurrent status epilepticus or pharmacoresistant epilepsy.

Conclusion: Epileptic seizures increase the energy requirements of the metabolically already compromised neurons establishing a vicious cycle resulting in worsening energy failure and neuronal death.

Keywords: Alpers syndrome; Déficit de la chaîne respiratoire; Epilepsy; Ketogen diet; Maladies mitochondriales; Mitochondrial disorders; Respiratory chain deficiency; Régime cétogène; Syndrome d’Alpers; Épilepsie.

Publication types

  • Review

MeSH terms

  • Adult
  • Ataxia / complications
  • Child
  • DNA Polymerase gamma
  • DNA-Directed DNA Polymerase / genetics
  • Diffuse Cerebral Sclerosis of Schilder / genetics
  • Epilepsy / diagnosis
  • Epilepsy / etiology*
  • Epilepsy / therapy
  • Humans
  • Mitochondrial Diseases / complications*
  • Mitochondrial Diseases / diagnosis
  • Mitochondrial Diseases / genetics
  • Mitochondrial Diseases / therapy
  • Muscle Weakness / complications
  • Mutation
  • Phenotype
  • Ubiquinone / deficiency


  • Ubiquinone
  • DNA Polymerase gamma
  • DNA-Directed DNA Polymerase
  • POLG protein, human

Supplementary concepts

  • Coenzyme Q10 Deficiency