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L-2-Hydroxyglutaric Aciduria (L-2-HA) - Yorkshire Terrier Type
| Acronym: | L-2-HGA |
| Gene: | L2HGDH |
| Mutation: | g.26760351A>G |
| Inheritance: | Autosomal Recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
L-2-Hydroxyglutaric Aciduria (L-2-HA) is a genetic neurometabolic disorder and part of a larger group of aciduria diseases characterized by the presence of abnormal organic acids as a result of an error in their metabolic pathway. This type of aciduria has been previously described in several dog breeds including Yorkshire Terrier dogs where it may produce a variety of clinical neurological deficits, including psychomotor retardation, seizures, and ataxia. Dogs affected with this inborn error of intermediary metabolism start to develop ataxia and seizures within the first few years of life. This type of Hydroxyglutaric Aciduria is caused by a mutation within the L2HGDH gene coding for the hydroxyglutaric acid dehydrogenase enzyme. L2HGDH is active in cells throughout the body, particularly in the brain, and muscles, and plays a crucial role in the L-2-Hydroxyglutaric Aciduria metabolism. The accumulation of that metabolite has been shown to induce oxidative stress in the cerebral and cerebellar cortices and to inhibit mitochondrial creatine kinase, reducing brain energy metabolism.
This type of muscle disorder found in Sheepdogs and Cattledogs is inherited as an autosomal recessive trait, requiring two copies of the mutated CLCN1 gene for the disease to develop. Dogs with only one copy of the mutated gene will not develop the disease but may act as carriers and pass the mutation to their offspring. Early genetic testing can help identify affected dogs that carry the mutation and prevent their further breeding by proper selection of mating pairs.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
CARRIER |
Tested mutation was detected in animal with „carrier“ result. Animal tested as carrier has one wild-type and one mutation allele, it is in heterozygous state. It will not develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
** Potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Farias, F. H., Zeng, R., Johnson, G. S., Shelton, G. D., Paquette, D., O Brien, D. P. (2012). A L2HGDH initiator methionine codon mutation in a Yorkshire terrier with L-2-hydroxyglutaric aciduria. BMC veterinary research, 8, 124. https://doi.org/10.1186/1746-6148-8-124
Sanchez-Masian, D. F., Artuch, R., Mascort, J., Jakobs, C., Salomons, G., Zamora, A., Casado, M., Fernandez, M., Recio, A., Lujan, A. (2012). L-2-hydroxyglutaric aciduria in two female Yorkshire terriers. Journal of the American Animal Hospital Association, 48(5), 366–371. https://doi.org/10.5326/JAAHA-MS-5967
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. (2007). L-2-hydroxyglutaric aciduria: characterisation of the molecular defect in a spontaneous canine model. Journal of medical genetics, 44(5), 334–340. https://doi.org/10.1136/jmg.2006.042507