Leigh syndrome: clinical features and biochemical and DNA abnormalities

Ann Neurol. 1996 Mar;39(3):343-51. doi: 10.1002/ana.410390311.


We investigated the etiology of Leigh syndrome in 67 Australian cases from 56 pedigrees, 35 with a firm diagnosis and 32 with some atypical features. Biochemical or DNA defects were determined in both groups, ie, 80% in the tightly defined group and 41% in the "Leigh-like" group. Eleven patients had mitochondrial DNA point mutations (nucleotide [nt] 8993 T to G, nt 8993 T to C, or nt 8344 A to G) and 1 Leigh-like patient had a heteroplasmic deletion. Twenty-nine patients had enzyme defects, ie, 13 respiratory chain complex I, 9 complex IV, and 7 pyruvate dehydrogenase complex (PDHC). Complex I deficiency is more common than recognized previously. Six PDHC-deficient patients had mutations in the X-chromosomal gene encoding the E1alpha subunit of PDHC. Parental consanguinity suggested autosomal recessive inheritance in two complex IV-deficient sibships. We found no strong correlation between the clinical features and basic defects. An assumption of autosomal recessive inheritance (frequently made in the past) would have been wrong in nearly one-half (11 of 28 tightly defined and 18 of 41 total patients) of those in whom a cause was found. A specific defect must be identified if reliable genetic counseling is to be provided.

MeSH terms

  • Brain / physiopathology
  • Child
  • Child, Preschool
  • Chromosome Aberrations / genetics*
  • Chromosome Disorders
  • Consanguinity
  • DNA, Mitochondrial / analysis
  • Diagnosis, Differential
  • Female
  • Gene Expression
  • Humans
  • Infant
  • Infant, Newborn
  • Lactates / blood
  • Lactates / cerebrospinal fluid
  • Leigh Disease / etiology*
  • Leigh Disease / genetics*
  • Leigh Disease / physiopathology
  • Liver / enzymology
  • Magnetic Resonance Imaging
  • Male
  • Muscle, Skeletal / enzymology
  • Point Mutation
  • Pyruvate Dehydrogenase Complex / blood
  • Pyruvate Dehydrogenase Complex / cerebrospinal fluid
  • Pyruvate Dehydrogenase Complex / metabolism
  • Pyruvate Dehydrogenase Complex Deficiency Disease
  • Tomography, X-Ray Computed
  • X Chromosome


  • DNA, Mitochondrial
  • Lactates
  • Pyruvate Dehydrogenase Complex