Spastic Paraplegia Type 5

Abstract

Spastic paraplegia type 5 (SPG5) is an autosomal recessive hereditary spastic paraplegia due to mutations in CYP7B1, which encodes oxysterol 7α‎-hydroxylase. Oxysterol 7α‎-hydroxylase is involved in the synthesis of bile acids from cholesterol. CYP7B1 mutations are responsible for rare forms of liver failure in infancy as well as lower motor neuron degeneration in adults with no obvious genotype-phenotype correlation. SPG5 is mostly characterized by spastic paraplegia with prominent posterior column sensory impairment that can lead to sensory ataxia and bladder dysfunction. SPG5 can easily be diagnosed thanks to the significant elevation of two plasma oxysterols: 27- and 25-hydroxycholesterol. Accordingly, plasma oxysterols are biomarkers that should be included in the screening of any spastic paraplegia of unknown etiology. Furthermore, the dramatic therapeutic response of a child with liver failure due to CYP7B1 mutations using chenodeoxycholic acid opens promising therapeutic perspectives for SPG5 patients, possibly as in cerebrotendinous xanthomatosis.