Type I glutaric aciduria, part 2: a model of acute striatal necrosis

Am J Med Genet C Semin Med Genet. 2003 Aug 15;121C(1):53-70. doi: 10.1002/ajmg.c.20008.


Type I glutaric aciduria (GA1) is an inborn error of organic acid metabolism that is associated with acute neurological crises, typically precipitated by an infectious illness. The neurological crisis coincides with swelling, metabolic depression, and necrosis of basal ganglia gray matter, especially the putamina and can be visualized as focal, stroke-like, signal hyperintensity on MRI. Here we focus on the stroke-like nature of striatal necrosis and its similarity to brain injury that occurs in infants after hypoxia-ischemia or systemic intoxication with 3-nitropropionic acid (NPA). These conditions share several features including abrupt onset, preferential effect in the striatum and age-specific susceptibility. The pathophysiology of the conditions is reviewed and a model proposed herein. We encourage investigators to test this model in an appropriate experimental system.

MeSH terms

  • Brain Diseases, Metabolic, Inborn / genetics*
  • Brain Diseases, Metabolic, Inborn / physiopathology*
  • Glutaryl-CoA Dehydrogenase
  • Humans
  • Magnetic Resonance Imaging
  • Models, Biological*
  • Necrosis
  • Neurotoxins / metabolism
  • Nitro Compounds
  • Oxidoreductases Acting on CH-CH Group Donors / deficiency*
  • Oxidoreductases Acting on CH-CH Group Donors / genetics
  • Oxidoreductases Acting on CH-CH Group Donors / metabolism
  • Propionates / metabolism
  • Putamen / pathology*


  • Neurotoxins
  • Nitro Compounds
  • Propionates
  • Oxidoreductases Acting on CH-CH Group Donors
  • Glutaryl-CoA Dehydrogenase
  • 3-nitropropionic acid