L-2- hydroxyglutaric aciduria (L-2-HGA) is an inherited neurometabolic disorder affecting dogs. Affected dogs have a Mutation in the Enzyme that breaks down L-2-hydroxyglutaric acid resulting in increased levels of L-2-hydroxyglutaric acid in urine, blood and Cerebrospinal Fluid and progressive damage to the brain. Affected dogs typically present between 4 months and one year of age with symptoms of neurologic disease including “wobbly” gait, tremors, seizures, muscle stiffness with exercise or excitement and changes in behavior. In some cases, affected dogs do not present with disease until later in life.
Genetic testing of the L2HGDH gene will reliably determine whether a dog is a genetic Carrier of L-2- hydroxyglutaric aciduria. L-2- hydroxyglutaric aciduria is inherited in an Autosomal Recessive manner in dogs meaning that they must receive two copies of the mutated gene (one from each parent) to develop the disease. In general, carrier dogs do not have features of the disease but when bred with another carrier of the same Mutation, there is a risk of having affected pups. Each pup that is born to this pairing has a 25% chance of inheriting the disease and a 50% chance of inheriting one copy and being a carrier of the L2HGDH gene mutation. Reliable genetic testing is important for determining breeding practices. In order to eliminate this mutation from breeding lines and to avoid the potential of producing affected pups, breeding of known carriers to each other is not recommended. Dogs that are not carriers of the mutation have no increased risk of having affected pups.
There may be other causes of this condition in dogs and a normal result does not exclude a different mutation in this gene or any other gene that may result in a similar genetic disease or trait.
Abramson CJ, Platt SR, Jakobs C, Verhoeven NM, Dennis R, Garosi L, Shelton GD.L-2-Hydroxyglutaric aciduria in Staffordshire Bull Terriers. J Vet Intern Med. 2003 Jul-Aug;17(4):551-6.
Short AD, Mellersh CS, Platt H, Carter SD, Timofte D, Lohi H, Ollier WE. Exonic mutations in the L2HGDH gene in Staffordshire bull terriers. Vet Rec. 2010 Sep 18; 167(12):455-7.