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L-2-Hydroxyglutaric Aciduria (L-2-HGA)
Breeds
Relevance Rating: There is strong evidence or research available for these breeds
Relevance Rating: The test is unknown, there is no evidence (i.e. research) available, or it has not been evaluated yet. These tests may or may not be meaningful for these breeds
GTPs
General
Disease Name
L-2-Hydroxyglutaric Aciduria (L-2-HGA)
OMIA
1371
Gene Name
L2HGDH
Gene Name 2
L2HGA
Mutation
c.1299C>T
Mutation 2
c.1297T>C
Mutation 3
c.1>A
Test Type
Genetic Disease/Disorder
Key Comments
Two separate publications identify identical mutation in a total of three affected Yorkshire Terriers. Organic acid analysis demonstrated accumulation of 2-HG in urine of affected dogs
Details
Symptoms include: seizures, difficulty walking, behaviour changes (hyperactivity, aggression, or dementia) Age of onset 6-12 months of age. Most dogs euthanised by 6 years of age, though variations in severity of symptoms and challenges with treatment could mean earlier euthanisation.
Details 2
To describe the development of clinical signs (CS) and outcome of L-2-hydroxyglutaric aciduria (L-2-HGA)... The mean age of CS onset was 12?months (range 2.5-60). Gait dysfunction was reported... with stiffness of all four limbs the most common... and earliest recognised abnormality. [also reported] Kyphosis, body and/or head tremors, and hypermetria were frequent. Behavioural changes were present... most commonly staring into space, signs of dementia, and loss of training... dogs demonstrated paroxysmal seizure-like/dyskinetic episodes. Nineteen (70 per cent) dogs were alive at a mean survival time of 76.6?months after onset of CS... Euthanasia occurred at a mean survival time of 44?months after onset of CS... L-2-HGA is considered a progressive neurological disease; however, CS can be successfully managed with affected dogs potentially living a normal lifespan. (From Shea et al, 2016) [clincial signs findings were owner reported, please see referenced research]
Published
Penderis, J., Calvin, J., Abramson, C., Jakobs, C., Pettitt, L., Binns, M.M., Verhoeven, N.M., O'Driscoll, E., Platt, S.R., Mellersh, C.S. : L-2-hydroxyglutaric aciduria: characterisation of the molecular defect in a spontaneous canine model. J Med Genet 44:334-40, 2007. Pubmed reference: 17475916. DOI: 10.1136/jmg.2006.042507.
Published 2
Shea, A., De Risio, L., Carruthers, H., Ekiri, A., Beltran, E. : Clinical features and disease progression of L-2-hydroxyglutaric aciduria in 27 Staffordshire bull terriers. Vet Rec :, 2016. Pubmed reference: 27729589. DOI: 10.1136/vr.103783.
Published 3
Bannasch, D., Young, A., Myers, J., Truv??, K., Dickinson, P., Gregg, J., Davis, R., Bongcam-Rudloff, E., Webster, M.T., Lindblad-Toh, K., Pedersen, N. : Localization of canine brachycephaly using an
Body/System/Process
Metabolic
OMIA Url
Inheritance
AR
Breed Specific Info
Researched Breeds
Staffordshire Bull Terrier, Yorkshire Terrier
Breed-specific 1
Staffordshire Bull Terrier
Breed-specific 1 Details
Publication demonstrated strong association between mutation and disease. Organic acid analysis demonstrated accumulation of 2-HG in urine of affected dogs. Penderis et al., (2007) L-2-hydroxyglutaric aciduria: characterisation of the molecular defect in a spontaneous canine model. Penderis, J., J. Calvin, C. Abramson, C. Jakobs, L. Pettitt, M. M. Binns, N. M. Verhoeven, E. O'Driscoll, S. R. Platt and C. S. Mellersh (2007). "L-2-hydroxyglutaric aciduria: characterisation of the molecular defect in a spontaneous canine model." Journal of Medical Genetics 44(5): 334-340.
Breed-specific 2
West Highland White Terrier
Breed-specific 2 Details
unpublished
Breed-specific 3
Yorkshire Terrier
Breed-specific details 3
Two separate publications identify identical mutation in a total of three affected Yorkshire Terriers. Organic acid analysis demonstrated accumulation of 2-HG in urine of affected dogs. Farias et al., (2012) A L2HGDH initiator methionine codon mutation in a Yorkshire terrier with L-2-hydroxyglutaric aciduria. Sanchez-Masian et al., (2012) L-2-hydroxyglutaric aciduria in two female Yorkshire terriers. Farias, F. H., R. Zeng, G. S. Johnson, G. D. Shelton, D. Paquette and D. P. O'Brien (2012). "A L2HGDH initiator methionine codon mutation in a Yorkshire terrier with L-2-hydroxyglutaric aciduria." BMC Vet Res 8: 124.; Sanchez-Masian, D. F., R. Artuch, J. Mascort, C. Jakobs, G. Salomons, A. Zamora, M. Casado, M. Fernandez, A. Recio and A. Lujan (2012). "L-2-hydroxyglutaric aciduria in two female Yorkshire terriers." J Am Anim Hosp Assoc 48(5): 366-371.
