P Roos1, K Svenstrup, E R Danielsen, C Thomsen, J E Nielsen. 1. Memory Disorders Research Group, Department of Neurology, Neurogenetics Clinic, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Abstract
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.
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 SPG5Apatients 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 delTp.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.
Authors: Ludger Schöls; Tim W Rattay; Peter Martus; Christoph Meisner; Jonathan Baets; Imma Fischer; Christine Jägle; Matthew J Fraidakis; Andrea Martinuzzi; Jonas Alex Saute; Marina Scarlato; Antonella Antenora; Claudia Stendel; Philip Höflinger; Charles Marques Lourenco; Lisa Abreu; Katrien Smets; Martin Paucar; Tine Deconinck; Dana M Bis; Sarah Wiethoff; Peter Bauer; Alessia Arnoldi; Wilson Marques; Laura Bannach Jardim; Stefan Hauser; Chiara Criscuolo; Alessandro Filla; Stephan Züchner; Maria Teresa Bassi; Thomas Klopstock; Peter De Jonghe; Ingemar Björkhem; Rebecca Schüle Journal: Brain Date: 2017-12-01 Impact factor: 13.501
Authors: Felipe Franco da Graça; Thiago Junqueira Ribeiro de Rezende; Luiz Felipe Rocha Vasconcellos; José Luiz Pedroso; Orlando Graziani P Barsottini; Marcondes C França Journal: Front Neurol Date: 2019-01-16 Impact factor: 4.003