ABSTRACT
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Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder of unknown cause primarily affecting anterior hom cells and descending motor pathways. Three forms of ALS have been defined: a familial form with autosomal dominant inheritance (familial ALS, FALS); a more frequent, nonhereditary "sporadic" form; and a form seen in the Mariana Islands in the Western Pacific which is often associated with Parkinson's disease and dementia. Although mutations in the Cu2•(ZIJ.2+ superoxide dismutase (SOD) gene have been detected in some pedigrees with FALS, FALS patients constitute less than I 0% of cases seen worldwide. Furthermore, the number of FALS pedigrees having the SOD mutation is likely around 15 to 20%. 1 Patients with the far more common sporadic (i.e., nonfamilial) form do not demonstrate abnormalities in the SOD gene. The pathogenic mechanisms underlying the sporadic form of ALS are unknown; however, some evidence supports a role for changes in concentrations of intracellular Ca2• ([Ca2•];) in ALS.2
