As was previously mentioned, an increased incidence of Parkinson's disease has not been shown anywhere in the world. However, there is an increased incidence of a complex of parkinsonism, dementia, and amyotrophic lateral sclerosis (ALS) in Guam, the Kii Peninsula of Japan, Rota, and the western highlands of New Guinea. This peculiar disease, in which patients manifest abnormalities referable to almost every level of the neuraxis, resembles a combination of parkinsonism, Alzheimer's disease, and ALS. Two major theories have emerged to explain the increased incidence of this condition in areas of the world bordered by the Mariana volcanic fault. The first theory implicates a secondary hyperparathyroidism, which increases the deposition of toxic environmental metals in the nervous system. This theory is supported by the finding of increased manganese and calcium levels in nervous tissue taken from patients dying of this condition. The secondary theory implicates the ingestion of two toxic amino acids - beta-oxaloamine-1-alanine (BOAA) and beta-methylamino-l-alanine (BMAA) - by people in this area of the world. This theory is supported by the finding that infusions of toxic amino acids can produce nervous system disease in primates that does seem to resemble some of the degenerative diseases including parkinsonism, ALS, and Alzheimer's disease. Further work needs to be done to clarify the role of these toxic amino acids, if any, in the pathogenesis of the Parkinson's disease-ALS-dementia complex on Guam. Both theories, implicating environmental factors as the cause, are supported by the fact that the incidence of this peculiar combination of disorders is steadily decreasing.

Bernard M. Patten

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