Open Access Highly Accessed Case report

A L2HGDH initiator methionine codon mutation in a Yorkshire terrier with L-2-hydroxyglutaric aciduria

Fabiana HG Farias1*, Rong Zeng1, Gary S Johnson1, G D Shelton2, Dominique Paquette3 and Dennis P O’Brien4

Author Affiliations

1 Department of Veterinary Pathobiology, University of Missouri, Columbia, USA

2 Department of Pathology, University of California at San Diego, La Jolla, USA

3 Centre Veterinaire DMV, Montreal, Canada

4 Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, USA

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BMC Veterinary Research 2012, 8:124  doi:10.1186/1746-6148-8-124

Published: 26 July 2012



L-2-hydroxyglutaric aciduria is a metabolic repair deficiency characterized by elevated levels of L-2-hydroxyglutaric acid in urine, blood and cerebrospinal fluid. Neurological signs associated with the disease in humans and dogs include seizures, ataxia and dementia.

Case presentation

Here we describe an 8 month old Yorkshire terrier that presented with episodes of hyperactivity and aggressive behavior. Between episodes, the dog’s behavior and neurologic examinations were normal. A T2 weighted MRI of the brain showed diffuse grey matter hyperintensity and a urine metabolite screen showed elevated 2-hydroxyglutaric acid. We sequenced all 10 exons and intron-exon borders of L2HGDH from the affected dog and identified a homozygous A to G transition in the initiator methionine codon. The first inframe methionine is at p.M183 which is past the mitochondrial targeting domain of the protein. Initiation of translation at p.M183 would encode an N-terminal truncated protein unlikely to be functional.


We have identified a mutation in the initiation codon of L2HGDH that is likely to result in a non-functional gene. The Yorkshire terrier could serve as an animal model to understand the pathogenesis of L-2-hydroxyglutaric aciduria and to evaluate potential therapies.

L-2-hydroxyglutaric aciduria; L2HGDH; Yorkshire terrier; Initiator methionine codon