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

Abstract

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).

• Authors: S Ferdinandusse, P Kostopoulos, S Denis, H Rusch, H Overmars, U Dillmann, W Reith, D Haas, R J A Wanders, M Duran, M Marziniak
• Journal: American journal of human genetics (Am J Hum Genet) Vol. 78 Issue 6 Pg. 1046-52 (Jun 2006) ISSN: 0002-9297 [Print] United States
• PMID: 16685654 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• Codon, Nonsense
• Fatty Acids
• Glucuronides
• sterol carrier proteins
• pristanic acid

Topics

• Adult
• Carrier Proteins (blood, genetics)
• Codon, Nonsense
• Dementia, Vascular (diagnosis, genetics)
• Dystonia (diagnosis, genetics)
• Fatty Acids (blood)
• Frameshift Mutation
• Glucuronides (urine)
• Humans
• Magnetic Resonance Imaging
• Male
• Polyneuropathies (diagnosis, genetics)
• Pons (pathology)
• Syndrome
• Thalamus (pathology)
• Torticollis (diagnosis, genetics)