Respiratory chain defects in hereditary spastic paraplegias

Hereditary Spastic Paraplegias (HSPs) are heterogeneous neurodegenerative d isorders whose etiopathogenesis is still unclear. The identification of pat hogenic mutations in a gene (SPG7) encoding a mitochondrial metalloprotease suggested that oxidative phosphorylation (OXPHOS) alterations might underl ie HSP in a subgroup of patients. We performed clinical, morphological, bio chemical, and molecular genetic studies in six HSP patients and in six spor adic patients to investigate OXPHOS in muscle biopsies. Complicated and pur e forms were included in our study. Morphological alterations of the type s een in OXPHOS-related disorders were found in three patients. Five patients showed an isolated defect of complex I activity. No mutations in the SPG7 gene were detected. Our results suggest that OXPHOS defects in HSP patients are more common than previously believed. (C) 2001 Elsevier Science B.V. A ll rights reserved.