The mutation at nt 8993 of mitochondrial DNA is a common cause of Leigh's syndrome

Ann Neurol. 1993 Dec;34(6):827-34. doi: 10.1002/ana.410340612.


Twelve patients with Leigh's syndrome from 10 families harbored a T > G point mutation at nt 8993 of mtDNA. This mutation, initially associated with neurogenic weakness, ataxia, and retinitis pigmentosa, was later found to result in the Leigh phenotype when present in a high percentage. In our patients, the mutation was heteroplasmic, maternally inherited, and appeared to segregate rapidly within the pedigrees. Quantitative analysis revealed a good correlation between percentage of mutant mitochondrial genomes and severity of the clinical phenotype. The mutation was not found in > 200 patients with other mitochondrial encephalomyopathies or in controls. Mitochondrial enzyme activities were normal in all but 1 patient, and there were no ragged-red fibers in the muscle biopsy. Lactic acidosis was present in 92% of patients. Our findings suggest that the mtDNA nt 8993 mutation is a relatively common cause of Leigh's syndrome.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Child
  • Child, Preschool
  • DNA, Mitochondrial / genetics*
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Leigh Disease / genetics*
  • Male
  • Pedigree
  • Point Mutation*


  • DNA, Mitochondrial