L-2-Hydroxyglutaric Aciduria

 

Gene: L2HGDH

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutations:

Staffordshire Bull Terrier mutation: Insertion, deletion, L2HGDH gene; c.1298_1300 del.ins CTT, p.(L433_H434 del.ins. PY), exon10

Yorkshire Terrier mutation: Substitution, L2HGDH gene; c.1 A>G

Medical system: Neurological

Breeds: Staffordshire Bull Terrier, Yorkshire Terrier

Age of onset of symptoms: 4 months to 1 year or later in life

L-2-hydroxyglutaric aciduria is a progressive neuro-metabolic disease caused by a deficiency of the L-2-hydroxyglutaric dehydrogenase enzyme.  In affected animals there is an accumulation of hydroxyglutaric acid in blood, urine and cerebrospinal fluid.  Clinical signs include ataxia, trembling, muscular rigidity, seizures, dementia and behavioral problems such as hyperactivity and aggression.  There is some case to case variation in severity of symptoms and progression of the disease.  Although some animals can respond positively to medical treatment, there is no cure and prognosis is guarded.

 

References:

OMIA link: [1371-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Shea A, De Risio L, Carruthers H, et al. (2016) Clinical features and disease progression of L-2-hydroxyglutaric aciduria in 27 Staffordshire bull terriers. Vet Rec 179(21):545 [pubmed/27729589]

Farias FH, Zeng R, Johnson GS, et al. (2012) A L2HGDH initiator methionine codon mutation in a Yorkshire terrier with L-2-hydroxyglutaric aciduria. BMC Vet Res 8:124. [pubmed/22834903]

Sanchez-Masian DF, Artuch R, Mascort J et al. (2012) L-2-hydroxyglutaric aciduria in two female Yorkshire Terriers.  JAAHA 48(5):366-370. [pubmed/22843824]

Short AD, Mellersh CS, Platt H, et al. (2010) Exonic mutations in the L2HGDH gene in Staffordshire bull terriers. Vet Rec. 167(12):455-7. [pubmed/20852250]

Penderis J, Calvin J, Abramson C, et al. (2007) L-2-hydroxyglutaric aciduria: characterization of the molecular defect in a spontaneous canine model.  J Med Genet 44:334-340. [pubmed/17475916]

Abramson CJ, Platt SR, Jakobs C, et al. (2003) L-2-Hydroxyglutaric aciduria in Staffordshire Bull Terriers. J Vet Intern Med. 17(4):551-6. [pubmed/12892307]