ORGANIC-ACIDS IN CEREBROSPINAL-FLUID AND PLASMA OF PATIENTS WITH L-2-HYDROXYGLUTARIC ACIDURIA

L-2-Hydroxyglutaric aciduria is a distinct inherited neurometabolic disorder leading to mental regression, seizures and severe cerebellar dysfunction, as well as pyramidal and extrapyramidal symptoms (Earth et al 1991, 1993). On neuroimaging, all patients show a characteristic pattern with severe progressive loss of myelinated arcuate fibres, cerebellar atrophy, and signal changes in the basal ganglia. The relationship of L-2-hydroxyglutarate to human metabolic pathways is so far unknown, and no other abnormalities are found on urinary organic acid analysis. In the search for the underlying metabolic defect a number of loading and fasting studies have been conducted in patients with L-2-hydroxyglutaric aciduria, with inconclusive results (Earth et al 1992, 1993). A refined method for the quantitative determination of organic acids in CSF and plasma was used in combination with stable isotope dilution assays to study samples from patients with L-2-hydroxyglutaric aciduria and to provide information on specific disturbances of cerebral metabolic pathways.