Mutations in the gene encoding peroxisomal sterol carrier protein X (SCPx) cause leukencephalopathy with dystonia and motor neuropathy.

In this report, we describe the first known patient with a deficiency of sterol carrier protein X (SCPx), a peroxisomal enzyme with thiolase activity, which is required for the breakdown of branched-chain fatty acids. The patient presented with torticollis and dystonic head tremor as well as slight cerebellar signs with intention tremor, nystagmus, hyposmia, and azoospermia. Magnetic resonance imaging showed leukencephalopathy and involvement of the thalamus and pons. Metabolite analyses of plasma revealed an accumulation of the branched-chain fatty acid pristanic acid, and abnormal bile alcohol glucuronides were excreted in urine. In cultured skin fibroblasts, the thiolytic activity of SCPx was deficient, and no SCPx protein could be detected by western blotting. Mutation analysis revealed a homozygous 1-nucleotide insertion, 545_546insA, leading to a frameshift and premature stop codon (I184fsX7).

Orbitofrontal involvement in the processing of unpleasant auditory information.

Although little is known about the contribution of the orbitofrontal cortex to the processing of new information in man, lesion studies in monkeys have suggested that it plays a critical role. The present study investigated changes in cerebral blood flow with positron emission tomography in normal human subjects during exposure to unpleasant auditory stimuli. The results indicated that the caudal orbitofrontal cortex, area 13, which is powerfully linked to the medial temporal limbic region and is involved in the regulation of autonomic responses, is a key part of the frontal cortex responding in the face of unpleasant incoming information.