Article Text

Download PDFPDF
l-2-hydroxyglutaric aciduria: characterisation of the molecular defect in a spontaneous canine model
  1. Jacques Penderis1,
  2. Jacqui Calvin3,
  3. Carley Abramson2,
  4. Cornelis Jakobs4,
  5. Louise Pettitt2,
  6. Matthew M Binns2,
  7. Nanda M Verhoeven4,
  8. Eamonn O’Driscoll3,
  9. Simon R Platt2,
  10. Cathryn S Mellersh2
  1. 1Institute of Comparative Medicine, Faculty of Veterinary Medicine, University of Glasgow, Glasgow, UK
  2. 2Animal Health Trust, Lanwades Park, Kentford, Newmarket, UK
  3. 3Biochemical Genetics Unit, Department of Clinical Biochemistry, Addenbrooke’s NHS Trust, Cambridge, UK
  4. 4Metabolic Unit, Department of Clinical Chemistry, VU University Medical Centre, De Boelelaan, Amsterdam, The Netherlands
  1. Correspondence to:
 Dr J Penderis
 Institute of Comparative Medicine, Faculty of Veterinary Medicine, University of Glasgow, Bearsden Road, Glasgow G61 1QH, UK; j.penderis{at}


l-2-hydroxyglutaric aciduria (l-2-HGA) is a neurometabolic disorder that produces a variety of clinical neurological deficits, including psychomotor retardation, seizures and ataxia. The biochemical hallmark of l-2-HGA is the accumulation of l-2-hydroxyglutaric acid (l-2-HG) in cerebrospinal fluid, plasma and urine. Mutations within the gene L2HGDH (Entrez Gene ID 79944) on chromosome 14q22 encoding L-2-hydroxyglutaric acid dehydrogenase have recently been shown to cause l-2-HGA in humans. Using a candidate gene approach in an outbred pet dog population segregating l-2-HGA, the causal molecular defect was identified in the canine homologue of L2HGDH and characterised. DNA sequencing and pedigree analysis indicate a common founder effect in the canine model. The canine model shares many of the clinical and MRI features of the disease in humans and represents a valuable resource as a spontaneous model of l-2-HGA.

  • GC, gas chromatography
  • l-2-HG, l-2-hydroxyglutaric acid
  • l-2-HGA, l-2-hydroxyglutaric aciduria

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Competing interests: None declared.