L-2-hydroxyglutaric aciduria: clinical heterogeneity versus biochemical homogeneity in a sibship

Neuropediatrics. 1997 Dec;28(6):314-7. doi: 10.1055/s-2007-973722.

Abstract

Three out of four sibs in a North-African family were affected with L-2-hydroxyglutaric aciduria. The youngest sib was most severely handicapped: she was diagnosed at 2.5 years of age, whereas the then 7- and 10-year-old siblings had a less pronounced psychomotor retardation. All patients had an increased head circumference in contrast to the healthy, non-affected sibling. Urine and plasma levels of L-2-hydroxyglutaric acid in the three sibs were similar and showed only a small variation. Magnetic resonance imaging (MRI) of the brain in the eldest sib showed hyperintense signal on T2-weighted images of the basal ganglia, dentate nucleus and subcortical white matter. The youngest sib showed identical white matter abnormalities of the corpus medullare cerebelli. These abnormalities were consistent with demyelination and/or spongiosis. On two occasions cerebrospinal fluid amino acid chromatography in the youngest sib showed an increased concentration of lysine and a decreased level of glutamine. Plasma lysine was normal. It is concluded that L-2-hydroxyglutaric aciduria is almost invariably associated with neurological disease; the severity of the symptoms does not seem to be completely dependent on the extent of the biochemical abnormalities and may even be variable within a family.

Publication types

  • Case Reports

MeSH terms

  • Ataxia / complications
  • Brain Diseases / complications
  • Brain Diseases / pathology
  • Child
  • Female
  • Glutarates / blood
  • Glutarates / urine*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Metabolism, Inborn Errors / complications
  • Metabolism, Inborn Errors / diagnosis
  • Metabolism, Inborn Errors / genetics*
  • Psychomotor Disorders / etiology

Substances

  • Glutarates