L-2-hydroxyglutaric Aciduria in Two Female Yorkshire Terriers

Abstract

Two female Yorkshire terrier puppies were presented with generalized tonic-clonic seizures and ataxia. MRI revealed bilaterally symmetrical, diffuse regions of gray matter hyperintensity on T2-weighted and fluid-attenuated inversion recovery sequences. Urinary organic acids were quantified by gas chromatography-mass spectroscopy and were consistent with a diagnosis of L-2-hydroxyglutaric aciduria (L2HGA). The L2HGDH gene encodes for the enzyme L-2-hydroxyglutarate dehydrogenase, which helps break down L-2-hydroxyglutaric acid. In both puppies described in this report, a homozygous mutation at the translation initiation codon of the homolog canine L2HGDH gene was detected (c.1A>G; p.Met1?), confirming the diagnosis of L2HGA at the DNA level. Canine L2HGA is caused by more than one mutation of L2HGDH, as reported in humans.

Clinical features and disease progression of L‐2‐hydroxyglutaric aciduria in 27 Staffordshire bull terriers

“…Development of primary brain tumours in human beings with L‐2‐HGA has been reported at an estimated frequency of 4.7 per cent (Patay and others 2012)—the incidence of primary brain tumours in the general human population varies worldwide with reports of 7 per 100,000 people (0.00007 per cent) and 18.1 per 100,000 people (0.0002 per cent) in the UK and the USA, respectively (McKinney 2004, Porter and others 2010). In affected dogs, the neurological deficits are similar, with CS consistent with cerebellar and forebrain dysfunction described (Abramson and others 2003, Garosi and others 2005, Scurrell and others 2008, Farias and others 2012, Sanchez‐Masian and others 2012). Since L‐2‐HGA was first described in SBTs in 2003, no further information regarding clinical progression or prognosis of affected dogs has been reported (Abramson and others 2003).…”

“…L2HG is reconverted to 2‐ketoglutarate by L‐2‐hydroxyglutaric dehydrogenase. Typically L‐2‐HGA results from dysfunction of L2HGDH—at present, 92 unique mutations of the gene encoding this enzyme have been reported in human beings (Database 2015) and four in dogs (Penderis and others 2007, Farias and others 2012, Sanchez‐Masian and others 2012). In SBTs, autosomal‐recessive mutations of the gene encoding L2HGDH have been identified, with substitution of two single nucleotides in exon 10 (c[1279T→C; 1299c→t]), resulting in exchange of the amino acids leucine and histidine for proline and tyrosine, respectively (Penderis and others 2007).…”

2-Hydroxyglutaric aciduria as a cause for seizure-like episodes in a domestic shorthair cat

“…4 L-2-HGA has been described in Staffordshire Bull Terriers, 2,3 a West Highland White Terrier 5 and Yorkshire Terriers. 6…”

Acidúria L2-hidroxiglutárica: circulação do gene em cães da raça Staffordshire Bull Terrier no Brasil em 2008-2015

“…Na Medicina Veterinária a maioria dos casos relatados foram em cães da raça SBT (Abramson et al 2003, Böhm et al 2014, mas também em três Yorkshire Terriers (Sanchez-Masian et al 2012, Farias et al 2012), e em um West Highland White Terrier (Garosi et al 2005). Garosi et al (2005), encontraram sinais clínicos neurológicos semelhantes aos descritos para esta enfermidade em um cão da raça West Highland White Terrier, o diagnóstico foi confirmado pelo aumento expressivo do ácido L-2-HG na urina e por meio dos achados de imagem de ressonância magnética.…”