L-2-Hydroxyglutaric aciduria presenting with severe autistic features

Brain Dev. 2008 Apr;30(4):305-7. doi: 10.1016/j.braindev.2007.09.005. Epub 2007 Nov 5.

Abstract

L-2-Hydroxyglutaric aciduria (L-2-HGA) is an autosomal recessive neurometabolic disorder characterized by psychomotor delay, ataxia, macrocephaly and typical neuroradiological findings of subcortical leucoencephalopathy. Recently, the disease causing gene has been discovered (L2HGDH) encoding L-2-hydroxyglutarate dehydrogenase. We present a 3-year-old boy with L-2-HGA, who demonstrated macrocephaly, noted already in utero with ultrasound. Cranial MRI demonstrated diffuse subcortical encephalopathy with increased signal of the subcortical white matter. Subsequent metabolic screening revealed increased levels of L-2-HGA, and genomic DNA analysis demonstrated two missense mutations in L-2-HGDG. Patient's further motor development was mildly impaired, whilst his speech development was profoundly impaired (first words at the age of 2 years). Since the age of 2 years he started demonstrating autistic repetitive behaviors and movements, increasing aloofness to his environment and limitations in the variety of spontaneous activity (CARS score: 44/60-severe autism). Autism has not so far been described in L-2-HGA and may be considered as an additional feature of the phenotypic spectrum.

Publication types

  • Case Reports

MeSH terms

  • Alcohol Oxidoreductases / genetics*
  • Amino Acid Metabolism, Inborn Errors / complications*
  • Amino Acid Metabolism, Inborn Errors / genetics*
  • Amino Acid Metabolism, Inborn Errors / urine
  • Autistic Disorder / etiology*
  • Autistic Disorder / genetics*
  • Autistic Disorder / urine
  • Brain / pathology
  • Glutarates / urine*
  • Humans
  • Infant
  • Magnetic Resonance Imaging
  • Male
  • Phenotype
  • Severity of Illness Index

Substances

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