Increased incidence of the Hfe mutation in amyotrophic lateral sclerosis and related cellular consequences

The etiology of amyotrophic lateral sclerosis (ALS) is unknown. The presence of mutations in the superoxide dismutase gene (SOD1) has led to theories regarding a role for oxidative stress in the pathogenesis of this disease. A primary cause of oxidative stress is perturbations in cellular iron homeostasis. Cellular iron mismanagement and oxidative stress are associated with a number of neurodegenerative diseases. One mechanism by which cells fail to properly regulate their iron status is through a mutation in the Hfe gene. Mutations in the Hfe gene are associated with the iron overload disease, hemochromatosis. In the current study, 31% of patients with sporadic ALS carried a mutation in the Hfe gene, compared to only 14% of patients without identifiable neuromuscular disease, or with neuromuscular diseases other than ALS ( p