Hallervorden-Spatz disease: cysteine accumulation and cysteine dioxygenase deficiency in the globus pallidus

Ann Neurol. 1985 Oct;18(4):482-9. doi: 10.1002/ana.410180411.


We describe neurochemical abnormalities found in the brains of 2 patients with autopsy-confirmed Hallervorden-Spatz (HS) disease. In 1 patient, contents of cystine and of glutathione-cysteine mixed disulfide in the globus pallidus were markedly elevated above values for appropriate control subjects. Activity of cysteine dioxygenase, which converts cysteine to cysteine sulfinic acid, was reduced in the globus pallidus, but normal in the frontal cortex and putamen of both patients. gamma-Aminobutyric acid content was markedly decreased in the globus pallidus and substantia nigra of both patients. These results suggest that cysteine accumulates locally in the globus pallidus in Hallervorden-Spatz disease as a result of an enzymatic block in the metabolic pathway from cysteine to taurine. Accumulated cysteine may chelate iron, accounting for the local increase in iron content in Hallervorden-Spatz disease. The combined excess of cysteine and ferrous iron may generate free radicals that damage neuronal membranes to cause the typical morphological changes observed in this disorder.

Publication types

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

MeSH terms

  • Adult
  • Amino Acids / cerebrospinal fluid
  • Amino Acids / metabolism
  • Basal Ganglia Diseases / metabolism*
  • Brain Chemistry
  • Cerebral Cortex / enzymology
  • Cerebral Cortex / metabolism
  • Child
  • Choline O-Acetyltransferase / metabolism
  • Cysteine / metabolism*
  • Cysteine Dioxygenase
  • Dioxygenases*
  • Dopamine / metabolism
  • Female
  • Globus Pallidus / enzymology
  • Globus Pallidus / metabolism*
  • Globus Pallidus / pathology
  • Humans
  • Male
  • Middle Aged
  • Oxygenases / deficiency*
  • Oxygenases / metabolism
  • Pantothenate Kinase-Associated Neurodegeneration / enzymology
  • Pantothenate Kinase-Associated Neurodegeneration / metabolism*
  • Pantothenate Kinase-Associated Neurodegeneration / pathology
  • Tissue Distribution


  • Amino Acids
  • Oxygenases
  • Dioxygenases
  • Cysteine Dioxygenase
  • Choline O-Acetyltransferase
  • Cysteine
  • Dopamine