Alternative titles; symbols
ORPHA: 163684;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 1p32.3 | ?Leukoencephalopathy with dystonia and motor neuropathy | 613724 | Autosomal recessive | 3 | SCP2 | 184755 |
A number sign (#) is used with this entry because of evidence that leukoencephalopathy with dystonia and motor neuropathy (LKDMN) is caused by homozygous mutation in the SCP2 gene (184755) on chromosome 1p32. One such patient has been reported.
Ferdinandusse et al. (2006) described the first known patient with deficiency of sterol carrier protein-2 (SCPx), a peroxisomal enzyme with thiolase activity, which is required for the breakdown of branched-chain fatty acids. The patient was a 45-year-old white man with a 28-year history of dystonic head tremor and spasmodic torticollis. He had noticed a stutter for the first time when he was 7 years old. At age 17 years, he observed a spasmodic torticollis to the left side, with a dystonic head tremor in stressful situations. During a fertility checkup by a urologist at the age of 29 years, hypergonadotrophic hypogonadism and azoospermia were diagnosed. One of 2 brothers was reported to have similar neurologic complaints. Cranial magnetic resonance imaging (MRI) showed bilateral hyperintense signals in the thalamus, butterfly-like lesions in the pons, and lesions in the occipital region. Neurologic examination revealed hyposmia, pathologic saccadic eye movements, and a slight hypoacusis. Deep tendon reflexes were brisk in the arms but diminished in the lower extremities. There were slight cerebellar signs, with left-sided intention tremor and rebound phenomenon. Metabolite analyses of plasma revealed an accumulation of branched-chain 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.
The transmission pattern of LKDMN in the family reported by Ferdinandusse et al. (2006) was consistent with autosomal recessive inheritance.
By mutation analysis of the SCP2 gene in a patient with leukoencephalopathy with dystonia and motor neuropathy, Ferdinandusse et al. (2006) identified a homozygous 1-bp insertion (545_546insA) (184755.0001).
Ferdinandusse, S., Kostopoulos, P., Denis, S., Rusch, H., Overmars, H., Dillmann, U., Reith, W., Haas, D., Wanders, R. J. A., Duran, M., Marziniak, M. Mutations in the gene encoding peroxisomal sterol carrier protein X (SCPx) cause leukencephalopathy with dystonia and motor neuropathy. Am. J. Hum. Genet. 78: 1046-1052, 2006. [PubMed: 16685654] [Full Text: https://doi.org/10.1086/503921]