Brain injury in glutaric aciduria type I: the value of functional techniques in magnetic resonance imaging

Eur J Paediatr Neurol. 2009 Nov;13(6):534-40. doi: 10.1016/j.ejpn.2008.12.002. Epub 2009 Jan 22.

Abstract

Background: Acute striatal necrosis is a devastating consequence of encephalopathic crisis in patients with glutaric aciduria type I (GA-I), but the mechanisms underlying brain injury are not completely understood.

Objective: To approach pathophysiological aspects of brain injury in GA-I by means of functional techniques in magnetic resonance imaging (MRI).

Patients and methods: Four patients during an acute encephalopathic crisis and three asymptomatic siblings with GA-I underwent single-voxel hydrogen magnetic resonance spectroscopy (MRS) and brain MRI including gradient echo T1-weighted, FLAIR, T2-weighted and diffusion-weighted imaging.

Results: The study was performed between three and eight days after the onset of acute encephalopathic crisis. Isotropic diffusion images showed high signal changes with corresponding low apparent diffusion coefficient values within the putamen, caudate nuclei and globus pallidus (four patients), and the cerebral peduncles including the substantia nigra (one patient). The study disclosed normal findings in asymptomatic siblings. MRS showed decreased N-acetyl-aspartate/creatine ratio at the basal ganglia in encephalopathic patients when compared to a group of sex- and age-matched controls.

Conclusions: Brain injury in GA-I is characterized by the presence of cytotoxic edema and reduced neuronal integrity by functional imaging techniques. Involvement of the basal ganglia may be asymmetrical in patients with unilateral motor disorder and may extent to the cerebral peduncles and substantia nigra, which may be responsible for the acute onset dystonia in some patients. Functional techniques failed to demonstrate any abnormalities in asymptomatic patients, which is in agreement with the integrity of basal ganglia structures observed by conventional MRI sequences.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Metabolism, Inborn Errors / complications*
  • Amino Acid Metabolism, Inborn Errors / diagnosis*
  • Amino Acid Metabolism, Inborn Errors / urine
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / metabolism
  • Brain / pathology
  • Brain Injuries / diagnosis*
  • Brain Injuries / etiology*
  • Brain Injuries / urine
  • Brain Mapping
  • Creatine / metabolism
  • Glutarates / metabolism
  • Glutarates / urine
  • Glutaryl-CoA Dehydrogenase / deficiency*
  • Glutaryl-CoA Dehydrogenase / genetics
  • Humans
  • Infant
  • Magnetic Resonance Imaging / methods
  • Magnetic Resonance Spectroscopy / methods
  • Retrospective Studies

Substances

  • 3-hydroxyglutaric acid
  • Glutarates
  • Aspartic Acid
  • N-acetylaspartate
  • Glutaryl-CoA Dehydrogenase
  • glutaric acid
  • Creatine