CYP7B1: novel mutations and magnetic resonance spectroscopy abnormalities in hereditary spastic paraplegia type 5A
Article first published online: 1 OCT 2013
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Acta Neurologica Scandinavica
Volume 129, Issue 5, pages 330–334, May 2014
How to Cite
CYP7B1: novel mutations and magnetic resonance spectroscopy abnormalities in hereditary spastic paraplegia type 5A. Acta Neurol Scand 2014: 129: 330–334. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd., , , , .
- Issue published online: 5 APR 2014
- Article first published online: 1 OCT 2013
- Manuscript Accepted: 28 AUG 2013
- Novo Nordisk Foundation
- Bevica Foundation
- Aase og Ejnar Danielsen Foundation
- hereditary spastic paraplegia;
- MR spectroscopy;
- magnetic resonance imaging
The SPG5A subtype of Hereditary Spastic Paraplegia (HSP) is a rare autosomal recessive neurodegenerative disorder caused by mutations in the CYP7B1 gene, which encodes a steroid cytochrome P450 7α-hydroxylase. This enzyme provides the primary metabolic route for neurosteroids. Clinically, SPG5A has been characterized as a pure form of HSP with a variable age of onset, but recently a broader spectrum of phenotypes has been described.
This study characterizes four unrelated SPG5A patients through clinical evaluation.
The investigations included blood biochemistry, electrophysiology, brain MRI and MR spectroscopy.
One patient had saccadic pursuit eye movements in addition to a pure HSP phenotype. Motor evoked potential (MEP) examinations revealed prolonged central conduction time. MRI of the brain showed white matter hyperintensities (WMH) in one patient. MRS showed elevated mI/Cr ratio in white matter in two patients; in the one patient with WMH and in one patient with normal MRI. Four novel mutations were identified; one frameshift (c.509 delT p.L170fs), one premature stop codon (c.334 C>T p.R112X), one amino acid changing (c.440 G>A p.G147D) and one duplication (c.945_947 dupGGC p.A316AA).
SPG5A could be characterized as a predominantly pure HSP. MRS showing elevated mI/Cr ratio in the white matter may be indicative of SPG5A.