The ALS/parkinsonism-dementia complex of Guam is a long latency disease with a diverse phenotypic expression characteristic of classical ALS, parkinsonism and dementia. It is remarkably similar to a syndrome localized to the Kii Peninsula of Japan. There are as yet no identified pathological features that will clearly distinguish the Guam or Kii ALS/PDC syndrome from other degenerative neurological disorders. At present, ALS/PDC of Guam and the Kii Peninsula can be confirmed only by postmortem examination. The most prominent pathological hallmark is the widespread occurrence of neurofibrillary tangles which express the same balance of 3R and 4R tau that is found in Alzheimer disease. They both show an increased prevalence of a peculiar retinal disorder termed linear retinal pigmentary epitheliopathy. The disorders are both highly familial. Several environmental factors have been proposed but no supportive evidence for an environmental or dietary factor has been found. Genome searches have so far failed to identify causative genes although two single nuclear polymorphisms related to MAPT that increase the risk of the Guam syndrome have been located. The two syndromes are clearly unique, and clues as to their causation could be beneficial in understanding the etiology of similar, but much more prevalent disorders in North America, Europe and Asia. Identification of biomarkers for premortem diagnosis would be helpful in management as well as in revealing the true etiology.
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