A metabolic defect affecting the central nervous system has recently been identified in young Staffordshire Bull Terriers. The cases identified to date (2 confirmed and 2 highly suspected) are between 6 months and 2 years of age and of both sexes. The animals showed an insidious progression of gait abnormalities (stiff and hypermetric gait; See video clip) and cerebral signs (dementia and/or seizures). MRI evaluation showed diffuse and marked hyperintensity of the cerebellar and cerebral grey matter on T2W images. T2 hyperintensity of the thalamus and brainstem was also found. (Figs 1 and 2). Urinary organic acid screening by gas chromatography-mass spectrometry revealed a marked excretion of 2-hydroxyglutaric acid. Further analysis showed this to be the L-isomer of 2-hydroxyglutaric acid (identified by Dr. Cornelis Jacobs).

L-2-hydroxyglutaric aciduria has been previously reported only in human beings. It is one of the rarer inborn errors of metabolism and is known to affect predominantly the white matter in humans. This disorder produces a slowly progressive encephalopathy which is often not recognized clinically until late childhood or early adulthood. It is distinct from the syndrome seen with the D-isomer of 2-hydroxyglutaric acid which results in a severe neonatal disorder. It is not known which metabolic pathway is involved in the production of L-2-hydroxyglutaric acid, although the lysine catabolic pathway has been implicated in some studies. There is no known treatment for the condition at this time.