Epilepsy in MT-ATP6 - related mils/NARP: correlation of elettroclinical features with heteroplasmy

Ann Clin Transl Neurol. 2021 Mar;8(3):704-710. doi: 10.1002/acn3.51259. Epub 2021 Jan 21.


The study aims to characterize the epilepsy phenotype of maternally inherited Leigh's syndrome (MILS) and neuropathy, ataxia, retinitis pigmentosa (NARP) due to mutations in the mitochondrial ATP6 gene and to correlate electroclinical features with mutant heteroplasmy load (HL). We investigated 17 individuals with different phenotype, from asymptomatic carriers to MILS: 11 carried the m.8993T> G mutation, 5 the m.8993T> C and one the novel, de novo m.8858G> A mutation. Seizures occurred in 37.5% of patients, EEG abnormalities in 73%. We ranked clinical and EEG abnormalities severity and performed quantitative EEG to estimate Abnormality Ratio (AR) and Spectral Relative Power (SRP). Spearman's rho and Kruskal-Wallis test were used for correlation with heteroplasmy load (HL). HL correlated with disease severity (Rho = 0.63, P = 0.012) and was significantly higher in patients with seizures or EEG abnormalities (P = 0.014). HL correlated with EEG severity score only for the m.8993T> G (Rho = 0.73, P = 0.040), showing a trend toward a positive correlation with AR and delta SPR, irrespective of the mutation.

Keywords: MT-ATP6 MT-ATP6; epilepsy; maternally inherited Leigh's syndrome (MILS); neuropathy, ataxia, retinitis pigmentosa (NARP); progressive myoclonic epilepsy (PME).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain Waves / physiology*
  • Child, Preschool
  • Female
  • Heteroplasmy / genetics*
  • Humans
  • Leigh Disease / genetics*
  • Leigh Disease / physiopathology*
  • Male
  • Middle Aged
  • Mitochondrial Myopathies / genetics*
  • Mitochondrial Myopathies / physiopathology*
  • Mitochondrial Proton-Translocating ATPases / genetics*
  • Pedigree
  • Retinitis Pigmentosa / genetics*
  • Retinitis Pigmentosa / physiopathology*
  • Severity of Illness Index


  • MT-ATP6 protein, human
  • Mitochondrial Proton-Translocating ATPases

Supplementary concepts

  • Maternally Inherited Leigh Syndrome
  • Neuropathy ataxia and retinitis pigmentosa

Grants and funding

This work was funded by Ministero della Salute grant .