CYP7B1: novel mutations and magnetic resonance spectroscopy abnormalities in hereditary spastic paraplegia type 5A

Acta Neurol Scand. 2014 May;129(5):330-4. doi: 10.1111/ane.12188. Epub 2013 Oct 1.


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.

Objective: This study characterizes four unrelated SPG5A patients through clinical evaluation.

Methods: The investigations included blood biochemistry, electrophysiology, brain MRI and MR spectroscopy.

Results: 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).

Conclusion: SPG5A could be characterized as a predominantly pure HSP. MRS showing elevated mI/Cr ratio in the white matter may be indicative of SPG5A.

Keywords: CYP7B1; MR spectroscopy; SPG5A; hereditary spastic paraplegia; magnetic resonance imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Brain / metabolism*
  • Brain / pathology
  • Cohort Studies
  • Cytochrome P450 Family 7
  • DNA Mutational Analysis
  • Evoked Potentials, Motor
  • Evoked Potentials, Somatosensory
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Magnetic Resonance Spectroscopy
  • Middle Aged
  • Mutation
  • Nerve Fibers, Myelinated / metabolism
  • Nerve Fibers, Myelinated / pathology
  • Neural Conduction / physiology
  • Spastic Paraplegia, Hereditary / genetics*
  • Spastic Paraplegia, Hereditary / pathology
  • Spastic Paraplegia, Hereditary / physiopathology*
  • Steroid Hydroxylases / genetics*
  • Young Adult


  • Steroid Hydroxylases
  • Cytochrome P450 Family 7
  • CYP7B1 protein, human

Supplementary concepts

  • Spastic Paraplegia 5a, Autosomal Recessive