An immigrant family with Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex.

Abstract

Amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) is a unique endemic on Guam island of the USA, the Kii Peninsula of Japan, and Papua state of Indonesia. The pathomechanism of ALS/PDC remains to be solved, although interaction between some environmental factors and genetic background is plausible. This is the first autopsy-proven immigrant family of ALS/PDC of the Kii Peninsula. A daughter and her father immigrated to the high incident area from outside the Kii Peninsula. The father developed ALS 18years later after immigration, and his daughter also developed ALS 65years after immigration. They showed pure ALS phenotype without parkinsonism and dementia. The daughter was diagnosed neuropathologically with Kii ALS/PDC with multiple proteinopathies: tauopathy, α-synucleinopathy, and TDP-43 proteinopathy. Gene analysis of familial ALS-related genes, including C9orf72, showed no mutation. The findings in an immigrant family established that certain environmental factors play a critical role in the pathogenesis of Kii ALS/PDC.