Our group is involved in the investigation of genetic disorders that cause neurological disease mostly in childhood. We use state-of the art mass spectrometry techniques to identify abnormal metabolites and proteins. From a knowledge of biochemical pathways we then identify candidate genes. The genes are sequenced and the effects of sequence alterations are determined by expression studies. Using these methods we have identified the genes responsible for pyridoxal phosphate-responsive epilepsy (PNPO), pyridoxine-dependent epilepsy (antiquitin), a disorder causing basal ganglia damage (hydroxy-isobutyryl-CoA hydrolase deficiency). Other diosrder we have helped to characterise include defects of cholesterol synthesis (e.g. Smith-Lemli-Opitz syndrome, desmosterolosis) and disorders of cholesterol catabolism e.g. alpha-methylacyl-CoA racemase deficiency. We have started looking at genetic disorders involving disturbed manganese homeostasis which can cause dystonia.