novel mutations and magnetic resonance spectroscopy abnormalities in hereditary spastic paraplegia type 5A
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.
Acta Neurologica Scandinavica, 2014, Vol 129, Issue 5, p. 330-4
Journal Article; Research Support, Non-U.S. Gov't; Adolescent; Adult; Brain; Cohort Studies; DNA Mutational Analysis; Evoked Potentials, Motor; Evoked Potentials, Somatosensory; Female; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Middle Aged; Mutation; Nerve Fibers, Myelinated; Neural Conduction; Spastic Paraplegia, Hereditary; Steroid Hydroxylases; Young Adult