L-2-hydroxyglutaric aciduria and brain tumors in children with mutations in the L2HGDH gene: neuroimaging findings

Neuropediatrics. 2008 Apr;39(2):119-22. doi: 10.1055/s-2008-1081217.

Abstract

L-2-Hydroxyglutaric aciduria (L-2-HGA, MIM 236792) is a rare autosomal recessive neurodegenerative disorder characterized by psychomotor delay, cerebellar and extrapyramidal signs and subcortical leukoencephalopathy with basal ganglia and dentate nuclei involvement. Mutations in the gene L2HGDH ( C14ORF160/DURANIN/) have been identified as causative for L-2-HGA. A feature disproportionally associated with L-2-HGA is the development of malignant brain tumors. In our cohort of 40 patients with L-2-HGA, two developed medulloblastoma and glioblastoma multiforme during the course of the disease. Two missense mutations in two patients were identified in the L2HGDH gene in exon 3 (c.292C-->T) and in exon 7 (c.887T-->A). Both mutations were present in the homozygous state. Serial MR imaging findings as well as MR spectroscopy imaging is reported in a patient who developed glioblastoma multiforme.

Publication types

  • Case Reports

MeSH terms

  • Alcohol Oxidoreductases / genetics*
  • Alcohol Oxidoreductases / metabolism
  • Amino Acid Metabolism, Inborn Errors / complications
  • Amino Acid Metabolism, Inborn Errors / genetics*
  • Amino Acid Metabolism, Inborn Errors / metabolism
  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / etiology
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Glutarates / metabolism
  • Humans
  • Magnetic Resonance Imaging
  • Magnetic Resonance Spectroscopy
  • Male
  • Mutation, Missense*

Substances

  • Glutarates
  • alpha-hydroxyglutarate
  • Alcohol Oxidoreductases
  • L2HGDH protein, human