Some 5–10% of ALS cases are familial (inherited) (Rowland 2000; Siddique et al. 1999). Most cases of familial ALS are inherited in an autosomal dominant fashion (that is, one affected parent carries the mutant gene for ALS and passes it to about half of his or her children) (Siddique et al. 1997). A small number of cases of familial ALS are inherited in an autosomal recessive fashion (that is, both unaffected parents carry a mutant gene and the disease affects about a quarter of their children). The specific gene mutations that cause most familial ALS cases are unknown, but about 20% of familial cases are believed to be caused by a mutation in a gene that encodes the enzyme superoxide dismutase 1 (Siddique and Deng 1996).

The majority of ALS cases are nonfamilial. The cause of nonfamilial ALS is unknown. Despite a number of epidemiologic studies that have examined occupations (for example, Italian professional soccer, farming, and electrical work), physical trauma, strenuous physical activity, lifestyle factors (for example, diet, cigarette use, and alcohol consumption), ethnic group, and socioeconomic status, there are no consistent findings (Armon 2003; Armon 2004; Chio et al. 2005; Rowland 2000; Valenti et al. 2005).

ALS-like diseases have been reported in Guam, the Kii peninsula of Japan, and Papua New Guinea (Banack and Cox 2003; Banack et al. 2006; Cox et al. 2003; Cox et al. 2005; Cox and Sacks 2002; Murch et al. 2004a; Murch et al. 2004b; Siddique et al. 1999). The causes of the ALS-parkinsonism-dementia complex of Guam and similar neurodegenerative diseases in the Kii peninsula of Japan and Papua New Guinea have not been identified. The pathology of these ALS-like diseases is different from that of ALS, and they will not be addressed in this report.


Several recent studies have reported a link between military service and ALS (Coffman et al. 2005; Haley 2003; Horner et al. 2003; Smith et al. 2000; Weisskopf et al. 2005). The Department of Veterans Affairs (VA) Office of Public Health and Environmental Hazards drafted an issue brief on that topic on

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