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

  title={Type I glutaric aciduria, part 2: A model of acute striatal necrosis},
  author={Kevin A Strauss and D. Holmes Morton},
  journal={American Journal of Medical Genetics Part C: Seminars in Medical Genetics},
  • K. Strauss, D. Morton
  • Published 15 August 2003
  • Biology
  • American Journal of Medical Genetics Part C: Seminars in Medical Genetics
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… 
Glutaric aciduria type 1: a clinician's view of progress.
  • K. Strauss
  • Biology, Medicine
    Brain : a journal of neurology
  • 2005
Six post-mortem brains from aboriginal Ojibway–Cree GA1 patients of Northern Canada are reported on to offer additional insight into the pathogenesis of the disorder to help develop an intervention strategy that could prevent the episode associated with acute striatal necrosis.
Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I.
Using a mouse model of GA-I, it is shown that pathologic events began in the neuronal compartment while enhanced lysine accumulation in the immature brain allowed increased glutaric acid production resulting in age-dependent injury.
Hallazgos neurorradiológicos de la Acidosis Glutárica tipo I
MR imaging found bilateral involvement of the putamina and periventricular white matter, and bilateral temporal atrophy and widened Silvian fissures in a 16 year-old girl with glutaric aciduria type I, who presented with a chronic dystonic syndrome and previously diagnosed of brain paralysis.
Neuropathological, biochemical and molecular findings in a glutaric acidemia type 1 cohort.
It is concluded that neuron loss occurs shortly after the encephalopathical crisis and does not progress, and the pathogenesis of selective neuronal loss cannot be explained on the basis of regional genetic and/or metabolic differences.
Glutaric Aciduria Type I: A Neuroimaging Diagnosis?
A previously healthy 17-month-old girl who presented with acute dystonia was diagnosed with glutaric aciduria type I and conventional T2-weighted and fluid-attenuated inversion recovery magnetic resonance images of the brain showed hyper-intensity in the caudates and putamina bilaterally with subtle involvement of the medial frontal lobes.
Mechanism of metabolic stroke and spontaneous cerebral hemorrhage in glutaric aciduria type I
Using a mouse model of GA1, it is shown that metabolic stroke progresses in the opposite sequence of ischemic stroke, with initial neuronal swelling and vacuole formation leading to cerebral capillary occlusion.
Dynamic changes of striatal and extrastriatal abnormalities in glutaric aciduria type I.
It is hypothesized that neuroradiological abnormalities and neurological symptoms in glutaric aciduria type I can be explained by overlaying episodes of cerebral alterations including maturational delay of the brain in utero, acute striatal injury during a vulnerable period in infancy and chronic progressive changes that may continue lifelong.
Pathogenesis of brain damage in glutaric acidemia type I: Lessons from the genetic mice model
Glutaric aciduria type I: value of diffusion-weighted magnetic resonance imaging for diagnosing acute striatal necrosis.
Diffusion-weighted MR imaging demonstrated more extensive disease than was apparent either on CT or on the conventional MR images, including bilateral involvement of the putamina, globus pallidus, and caudate nuclei, consistent with acute necrosis of the corpus striatum and lentiform nuclei.


Evaluation of trigger factors of acute encephalopathy in glutaric aciduria type I: Fever and tumour necrosis factor-α
Investigating the influence of temperature and TNF-a on neuronal damage induced by 3-hydroxyglutaric (3-OH-GA) and glutaric acids (GA) in vitro found that brain temperature modulates the outcome of ischaemic brain injury.
3-Hydroxyglutaric and glutaric acids are neurotoxic through NMDA receptors in vitro
It is hypothesized that the age- and regional specific brain damage in GDD could be caused by overstimulation of NMDA receptors and subsequent excitotoxic cell death and whether neurotoxic effects could be prevented by NMDA and non-NMDA receptor antagonists.
Neuropathology of Propionic Acidemia: A Report of Two Patients With Basal Ganglia Lesions
Examination of the brain of the 35-month-old boy and 9-year-old girl showed vascular and parenchymal mineralization, focal pallor and spongy change, and foci of acute neuronal injury, similar to those previously described.
Nerve cell lesions caused by 3-hydroxyglutaric acid: A possible mechanism for neurodegeneration in glutaric acidaemia I
In organotypic slice cultures from rat brain expressing different glutamate receptor subtypes, whether glutaric, 3-hydroxyglutaric or glutaconic acids are neurotoxic and if this neurotoxicity is related to excitotoxic mechanisms was tested.
Acute encephalopathy with bilateral striatal necrosis. A distinctive clinicopathological condition.
Two patients with acute encephalopathy with bilateral striatal necrosis are presented and the literature on the subject is reviewed, finding an infectious or para-infectious mechanism seems to be the most likely possibility.
Biochemical, pathologic and behavioral analysis of a mouse model of glutaric acidemia type I.
The phenotype of a mouse model of GA-I generated via targeted deletion of the Gcdh gene in embryonic stem cells is described, where the affected mice have a mild motor deficit but do not develop the progressive dystonia seen in human patients.
Glutaric aciduria type 1 an atypical presentation together with some observations upon treatment and the possible cause of cerebral damage.
The possible role of quinolinic acid in the genesis of the fronto temporal and striatal atrophy is discussed and measurement of the quinolinate concentration in cerebrospinal fluid (CSF) of this case and age-related controls is presented.
Acute encephalopathy with bilateral striatal necrosis: favourable response to corticosteroid therapy.
Glutaric aciduria type I: Pathomechanisms of neurodegeneration
It is speculated that 3-hydroxyglutaric acid induces a mild energy deprivation that interferes with the voltage-dependent Mg2+-block of NMDA receptors.