CYP 7 B 1 : novel mutations and magnetic resonance spectroscopy abnormalities in hereditary spastic paraplegia type 5 A

The SPG 5 A subtype of H ereditary S pastic P araplegia ( HSP ) is a rare autosomal recessive neurodegenerative disorder caused by mutations in the CYP 7B1 gene, which encodes a steroid cytochrome P 450 7α‐hydroxylase. This enzyme provides the primary metabolic route for neurosteroids. Clinically, SPG 5 A 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 SPG 5 A 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 m I /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 del T 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 m I / C r ratio in the white matter may be indicative of SPG 5 A .