A case of myelopathy, myopathy, peripheral neuropathy and subcortical grey matter degeneration associated with recessive compound heterozygous POLG1 mutations

Neuromuscul Disord. 2012 May;22(5):401-5. doi: 10.1016/j.nmd.2011.10.017. Epub 2012 Feb 21.

Abstract

This 54year old woman presented with symptoms of sensory ataxic neuropathy, with cerebellar features. She developed further weakness, visual disturbances with diplopia, dysarthria and dysphasia. After her death at 66years, she was found to have compound heterozygous mutations of POLG1 gene in muscle, and Southern blot showed low levels of multiple deletions of mitochondrial DNA. Neuropathological examination showed profound dorsal column and dorsal spinocerebellar tract degeneration, degeneration of dorsal root ganglia and Clarke's nucleus in spinal cord and severe predominantly sensory peripheral neuropathy. The brain showed severe neuronal loss and gliosis in substantia nigra, medial posterior thalamus and head of caudate. Excess numbers of COX-negative fibres and "ragged-red" fibres were found in five skeletal muscles sampled.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • DNA Polymerase gamma
  • DNA, Mitochondrial / genetics
  • DNA-Directed DNA Polymerase / genetics*
  • Fatal Outcome
  • Female
  • Genes, Recessive / genetics
  • Genetic Predisposition to Disease / genetics*
  • Heterozygote
  • Humans
  • Middle Aged
  • Muscular Diseases / diagnosis
  • Muscular Diseases / genetics*
  • Mutation*
  • Peripheral Nervous System Diseases / diagnosis
  • Peripheral Nervous System Diseases / genetics*
  • Peripheral Nervous System Diseases / pathology
  • Spinal Cord Diseases / diagnosis
  • Spinal Cord Diseases / genetics*
  • Spinal Cord Diseases / pathology
  • Spinocerebellar Degenerations / genetics*
  • Spinocerebellar Degenerations / pathology

Substances

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