TY - JOUR

T1 - CYP7B1

T2 - novel mutations and magnetic resonance spectroscopy abnormalities in hereditary spastic paraplegia type 5A

AU - Roos, P

AU - Svenstrup, K

AU - Danielsen, E R

AU - Thomsen, C

AU - Nielsen, J E

N1 - © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PY - 2014/5

Y1 - 2014/5

N2 - UNLABELLED: 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.

AB - UNLABELLED: 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.

U2 - 10.1111/ane.12188

DO - 10.1111/ane.12188

M3 - Journal article

C2 - 24117163

VL - 129

SP - 330

EP - 334

JO - Acta Neurologica Scandinavica

JF - Acta Neurologica Scandinavica

SN - 0001-6314

IS - 5

ER -