L-2-hydroxyglutaric Acidemia

l-2-Hydroxyglutaric aciduria (l-2-HGA) is a hereditary neurometabolic disorder reported in human beings and dogs characterized by spongiform changes in the brain which affect the gray matter of the cerebral cortex, thalamus, cerebellum and brain stem. The disease is caused by increased L-2-Hydroxyglutaric acid concentration in cerebrospinal fluid (CSF) and to a lesser extent in blood plasma. L-2-Hydroxyglutaric aciduria (L-2-HGA) is characterized by progressive deterioration of central nervous system function including epilepsy and abnormal enlargement of the head and brain (macrocephaly) in many cases. In dogs, the disease has been described in the Staffordshire Bull Terrier.

Clinical signs include mild motor and neurological abnormalities in the first years of life, followed by progressive poor coordination of limbs, imperfect coordination of throat, tongue, or face muscles, tremors, seizures, and moderate to severe mental deterioration. Clinical signs are usually apparent between 6 months and one year, although they can appear later. The diagnosis is confirmed by the finding of an excess of L-2-hydroxyglutaric acid in urine, blood and cerebrospinal fluid (CSF). L-2-hydroxyglutaric aciduria should be considered as one of the alternative diagnoses of epilepsy. The canine disease shares many of the clinical and MRI features of the disease in humans. In one case report, a 6-month-old, female Cavalier King Charles Spaniel exhibited seizures that were difficult to control with standard anticonvulsants over a 12-month period. The diagnosis of an organic aciduria with excessive excretion of hexanoylglycine was determined when the dog was 20 months old. Recurrent and cluster seizures were eventually controlled with the addition of other medications.


  1. 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
  2. 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
  3. 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
  4. Epilepsy in a Young Adult Caused by L-2-Hydroxyglutaric Aciduria: A Case Report. Vembu Periasamya, Mohd Rudwanb, Girish Yadavc, Riyadh A. Khana
  5. Refractory Seizures Associated With an Organic Aciduria in a Dog. Simon Platt, BVM&S;, MRCVS, Diplomate ACVIM (Neurology), Diplomate ECVN, Yvonne L. McGrotty, BVMS, CertSAM, MRCVS, Carley J. Abramson, DVM, Diplomate ACVIM (Neurology) and Cornelis Jakobs, PhD. In: Journal of the American Animal Hospital Association 43:163-167 (2007)