Get access

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

Authors

  • P. Roos,

    Corresponding author
    1. Memory Disorders Research Group, Department of Neurology, Neurogenetics Clinic, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
    • P. Roos, Memory Disorders Research Group, Department of Neurology, Section 6911, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhajen, Denmark

      Tel.: +45 35346702

      Fax: +45 35452446

      e-mail:peterroos76@gmail.com

    Search for more papers by this author
  • K. Svenstrup,

    1. Memory Disorders Research Group, Department of Neurology, Neurogenetics Clinic, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
    2. Section of Neurogenetics, Department of Cellular and Molecular Medicine, The Panum Institute, University of Copenhagen, Copenhagen, Denmark
    Search for more papers by this author
  • E. R. Danielsen,

    1. Department of Radiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
    Search for more papers by this author
  • C. Thomsen,

    1. Department of Radiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
    Search for more papers by this author
  • J. E. Nielsen

    1. Memory Disorders Research Group, Department of Neurology, Neurogenetics Clinic, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
    2. Section of Neurogenetics, Department of Cellular and Molecular Medicine, The Panum Institute, University of Copenhagen, Copenhagen, Denmark
    Search for more papers by this author

Abstract

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.

Ancillary