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The term hereditary spastic paraplegia (HSP) is used to describe a group of clinically and genetically heterogeneous disorders in which the defining clinical feature is progressive spasticity and weakness of the lower limbs. The phenotype is traditionally classified as “pure” when symptoms and signs are generally confined to those of a progressive spastic paraparesis, or “complicated” when associated with additional neurological or other clinical features.1 Inheritance may be autosomal dominant, autosomal recessive, or rarely X linked. Overall autosomal dominant inheritance is most commonly associated with pure forms of the disease, whereas autosomal recessive HSP shows greater phenotypic variability, including several well defined syndromes.2,3
To date nine autosomal recessive HSP loci have been identified and causative mutations found in three genes: SPG7 (paraplegin), SPG20 (spartin), and SPG21 (maspardin). SPG7 encodes paraplegin, a mitochondrial protein, which is a member of the AAA protein superfamily (ATPase associated with diverse cellular activities) and is homologous to a number of yeast mitochondrial metalloproteases.4 SPG7 mutations may result in either pure or complicated HSP phenotypes.4,5 Muscle biopsy analysis of patients with SPG7 mutations may show histological evidence of mitochondrial dysfunction4,6 and recently biochemical studies have shown specific defects in mitochondrial respiratory chain function.5,7
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