Elevated hydroxycholesterols in Norwegian patients with hereditary spastic paraplegia SPG5.

Abstract

Spastic paraplegia type 5 (SPG5/HSP-CYP7B1) is an autosomal recessive hereditary spastic paraplegia (HSP) caused by biallelic variants in the CYP7B1 gene, resulting in dysfunction of the enzyme oxysterol-7-α-hydroxylase. The consequent accumulation of hydroxycholesterols in plasma seems to be pathognomonic for SPG5, and represent a possible target for treatment. We aimed to characterize Norwegian patients with SPG5, including clinical examinations, genetic analyses, measurements of hydroxycholesterols, electrophysiological investigations and brain imaging. Five unrelated patients carried presumed disease-causing variants in CYP7B1, three of the variants were novel. Four patients presented with pure HSP, one with complex HSP. The three tested patients all had markedly increased levels of 25- and 27-hydroxycholesterol in plasma. Our results suggest that the clinical examination is still the best approach to classify disease severity in patients with SPG5. Plasma hydroxycholesterols were elevated, thus presenting as potentially valuable diagnostic biomarkers, in particular in patients where genetic analyses are inconclusive.

• Authors: Sjur Prestsæter, Jeanette Koht, Foudil Lamari, Chantal M E Tallaksen, Stian Tobias Juel Hoven, Magnus Dehli Vigeland, Kaja Kristine Selmer, Siri Lynne Rydning
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 419 Pg. 117211 (Dec 15 2020) ISSN: 1878-5883 [Electronic] Netherlands
• PMID: 33160247 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.

Chemical References

• Hydroxycholesterols

Topics

• Brain
• Genetic Testing
• Humans
• Hydroxycholesterols
• Mutation
• Pedigree
• Severity of Illness Index
• Spastic Paraplegia, Hereditary (genetics)