Autosomal dominant chorea-acanthocytosis with polyglutamine-containing neuronal inclusions

Neurology. 2002 Apr 9;58(7):1031-7. doi: 10.1212/wnl.58.7.1031.

Abstract

Background: The term chorea-acanthocytosis describes a heterogeneous group of neurodegenerative disorders with variable clinical features and modes of inheritance. The characteristic acanthocytic appearance of red blood cells is attributed to abnormalities of a membrane protein, band 3, although the relationship between this and the neurodegenerative process has yet to be determined.

Objective: To describe features of phenotype, inheritance, and neuropathological findings in a family with this disorder.

Methods: Clinical and hematologic evaluations were performed on all available family members and neuropathological examination was performed on one case.

Results: Autosomal dominant inheritance was evident, with variable clinical features of chorea or parkinsonism, marked cognitive changes, but no seizures or peripheral neurologic abnormalities. Abnormalities of band 3 were demonstrated on gel electrophoresis of red blood cell membranes. Neuropathological examination revealed severe neuronal loss of the caudate-putamen and intranuclear inclusion bodies in many areas of the cerebral cortex. These inclusion bodies were immunoreactive for ubiquitin, expanded polyglutamine repeats, and torsinA.

Conclusions: This family extends the genetic spectrum of chorea-acanthocytosis to include autosomal dominant inheritance, possibly due to expanded trinucleotide repeats. Intraneuronal inclusion bodies have recently been associated with a wide range of inherited neurodegenerative disorders and may provide a clue to etiopathogenesis, in addition to potentially indicating a function of torsinA.

Publication types

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

MeSH terms

  • Acanthocytes / pathology
  • Adult
  • Atrophy
  • Cerebral Cortex / chemistry
  • Cerebral Cortex / pathology
  • Chorea / genetics*
  • Chorea / pathology*
  • Female
  • Humans
  • Inclusion Bodies / chemistry*
  • Inclusion Bodies / genetics
  • Inclusion Bodies / pathology*
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Neurons / chemistry
  • Neurons / pathology*
  • Pedigree
  • Peptides / analysis*

Substances

  • Peptides
  • polyglutamine