L-2-hydroxyglutaricacidemia (L-2-HGA)

What is L-2-hydroxyglutaricacidemia in dogs


Chevromist Canine brain regionsL-2-hydroxyglutaricacidemia (L-2-HGA), also known as organic aciduria is a neurometabolic disorder affecting dogs. Dogs affected by L-2-hydroxyglutaricacidemia have a mutation in the enzyme responsible for breaking down L-2-hydroxyglutaric acid in the body. This leads to increased concentrations of L-2-hydroxyglutaric acid levels in the blood, urine and most damaging of all, the cerebrospinal fluid. The high levels in the cerebrospinal fluid causes progressive damage to the grey matter of the brain of the affected dog. L-2-hydroxyglutaricacidemia (L-2-HGA) usually starts to affect dogs early in life from about 4 months of age, getting progressively worse and is ultimately fatal. Currently, there is no cure for L-2-hydroxyglutaricacidemia (L-2-HGA).

Genetics of L-2-hydroxyglutaricacidemia

L-2-hydroxyglutaricacidemia is an autosomal recessive disease caused by changes in the L2HGDH gene in dogs. Being an autosomal recessive disease means the affected dog must have 2 copies of the mutated form of the L2HGDH gene to be affected by the disease. If just one of the parents of a litter are clear of any mutated L2HGDH genes then no puppies in the litter will be affected.

Severity of L-2-hydroxyglutaricacidemia in dogs

L-2-hydroxyglutaricacidemia is a highly severe neurological disease that affects dogs while they are young and greatly reduces their quality of life as well as the length of life in an affected dog. Most affected dogs will have to be euthanized as a result of the progressing symptoms.

What are the symptoms of L-2-hydroxyglutaricacidemia in dogs?

L-2-hydroxyglutaricacidemia mainly affects the central nervous system of an affected dog, so naturally, most of the symptoms will be a result of a damaged neurological system. Initial clinical symptoms will include motor and neurological abnormalities that progress with time to poor coordination in all the limbs with the hind legs being most affected. This poor coordination can also affect the throat, tongue and facial muscles. The disease then progresses into symptoms such as muscle stiffness, tremors, seizures and mental deterioration that also progresses in severity as the level of damage to the brain increases. Affected dogs will also go through other personality or behavioural changes depending on which parts of the brain are affected earlier or more severely.

Diagnosis of L-2-hydroxyglutaricacidemia (L2-HGA)

Urine Test ChevromistDiagnosis of L-2-hydroxyglutaricacidemia (L2-HGA) is often made by testing the urine, blood or cerebral spinal fluid (CSF) for the presence of L-2-hydroxyglutaric acid. If there is any present, it is usually a clear sign that the dog is affected by L-2-hydroxyglutaricacidemia. Often the dog is suspected of having epilepsy and this test is used to give a more definitive diagnosis. To confirm this diagnosis, a DNA test for the faulty L2HGDH gene can be performed to certify if the tested dog is/will be affected, is a carrier or is clear of the disease.

Treatment of dogs with L-2-hydroxyglutaricacidemia (L2-HGA)

Unfortunately, treatment of dogs affected by L-2-hydroxyglutaricacidemia (L2-HGA) is limited to treating the symptoms and providing as much care as possible to make the dog’s life as comfortable as possible. Some drugs used to treat epilepsy may be effective in reducing the severity of the seizures but so far even this drug treatment has had limited and varied results.

Resources

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

Effects of L-2-Hydroxyglutaric Acid on Various Parameters of the Glutamatergic System in Cerebral Cortex of Rats In: Metabolic Brain Disease. DOI 10.1023/A:1025559200816

Epilepsy in a Young Adult Caused by L-2-Hydroxyglutaric Aciduria: A Case Report. Vembu Periasamya, Mohd Rudwanb, Girish Yadavc, Riyadh A. Khana

L-2-hydroxyglutaric aciduria and brain malignant tumors. A predisposing condition? I. Moroni, MD, M. Bugiani, MD, L. D’Incerti, MD, C. Maccagnano, MD, M. Rimoldi, PhD, L. Bissola, PhD, B. Pollo, MD, G. Finocchiaro, MD and G. Uziel, MD. In: NEUROLOGY 2004;62:1882-1884

Neuropathological Findings in a Staffordshire Bull Terrier with l-2-Hydroxyglutaric Aciduria. E. Scurrell, E. Davies†, E. Baines†, G.B. Cherubini, S. Platt§, W. Blakemore, A. Williams and S. Schöniger. doi:10.1016/j.physletb.2003.10.071

Penderis J, Calvin J, Abramson C, Jakobs C, Pettitt L, Binns MM, Verhoeven NM, O’Driscoll E, Platt SR, Mellersh CS. (2007) L-2-hydroxyglutaric aciduria: characterisation of the molecular defect in a spontaneous canine model. J Med Genet. 44(5):334-40

Refractory Seizures Associated With an Organic Aciduria in a Dog. Simon Platt, Yvonne L. McGrotty, Carley J. Abramson and Cornelis Jakobs, PhD. In: Journal of the American Animal Hospital Association 43:163-167 (2007)

Scurrell E, Davies E, Baines E, Cherubini GB, Platt S, Blakemore W, Williams A, Schöniger S. (2008) Neuropathological findings in a Staffordshire bull terrier with l-2-hydroxyglutaric aciduria. J Comp Pathol. 138(2-3):160-4

Shires PK, Nafe LA, Hulse DA. (1983) Myotonia in a Staffordshire terrier. Journal of the American Veterinary Medical Association 183: 229

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

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