Human pathology

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autosomal recessive hereditary spastic paraplegia

Muscle biopsies from the autosomal recessive form of patients with hereditary spastic paraplegia revealed histochemical signs of a mitochondrial disorder, namely RRFs, COX-negative fibres and succinate dehydrogenase-positive hyperintense fibres.

Linkage and subsequent mutation analysis revealed large deletions in a gene dubbed paraplegin. Owing to the homology with a yeast mitochondrial ATPase with both proteolytic and chaperone-like activities, it has been suggested that this form of hereditary spastic paraplegia could be a neurodegenerative disorder due to OXPHOS deficiency, attributing a putative function in the assembly or import of respiratory chain subunits or cofactors to paraplegin.