Mutations in the gene encoding peroxisomal sterol carrier protein X (SCPx) cause leukencephalopathy with dystonia and motor neuropathy
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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).
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Only for SCPx, the thiolase required for breakdown of branched-chain fatty acids, a single patient with deficiency has been described.
“However, only for SCPx, the thiolase required for the breakdown of branched-chain fatty acids, a single patient with a deficiency of the enzyme (MIM #613724) has been described so far [102].”
From Peroxisomes in brain development and function (2016) · cites this paper as [102]
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An Unusual Retinal Phenotype Associated With a Mutation in Sterol Carrier Protein SCP2
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- Authors
- Ferdinandusse, S., Kostopoulos, P., Denis, S., Rusch, H., Overmars, H., Dillmann, U., Reith, W., Haas, D., Wanders, R. J. A., Duran, M., & Marziniak, M.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Saarland University (DE)
- Heidelberg University (DE)
- Corresponding author
- Ferdinandusse, S.
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2006-06
- Volume
- 78
- Issue
- 6
- Pages
- 1046-1052
- ISSN
- 0002-9297 (ISSN-L)
- OpenAlex
- W2136674380
- Cited by
- 145
- References
- 20
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 8 · 2023: 3 · 2022: 11 · 2021: 7 · 2020: 7 · 2019: 10 · 2018: 8 · 2017: 7 · 2016: 13 · 2015: 11 · 2014: 7 · 2013: 7 · 2012: 6
- FWCI
- 5.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- PubMed (publishedVersion)
- UCLA - Biblioteca de Ciencias de la Salud (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (916.46.109)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- dystonia, motor neuropathy, torticollis, frameshift mutation, peroxisomal disorders, azoospermia, hyposmia
- MeSH terms
- Adult, Carrier Proteins, Dystonia, Fatty Acids, Humans, Magnetic Resonance Imaging, Male, Polyneuropathies, Pons, Syndrome, Thalamus, Torticollis, Dementia, Vascular, Frameshift Mutation, Codon, Nonsense, Glucuronides
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