Yasumasa Kokubo1, Satoru Morimoto2, Ryogen Sasaki3, Masato Hasegawa4, Hiroyuki Ishiura5, Shoji Tsuji5, Mari Yoshida6, Naohisa Yamazoe7, Mitsukazu Miyazaki7, Shigeki Kuzuhara8. 1. Kii ALS/PDC Research Center, Graduate School of Regional Innovation Studies, Mie University, 1577, Kurima-machiyamachiMie prefecture, Tsu, 514-8507, Japan. kokubo7011@gmail.com. 2. Department of Oncologic Pathology, Mie University School of Medicine, Tsu, 514-8507, Japan. 3. Department of Neurology, Kuwana City Medical Center, Kuwana, 511-0061, Japan. 4. Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, Tokyo, 156-8506, Japan. 5. Department of Neurology, Graduate School of Medicine, University of Tokyo, Tokyo, 113-8655, Japan. 6. Institute for Medical Science of Aging, Aichi Medical University, Nagakute, 480-1195, Japan. 7. Department of Internal Medicine, Minami-Ise Hospital, Minamiise, 516-0101, Japan. 8. Department of Neurology and Medicine, School of Nursing, Suzuka University of Medical Science, Suzuka, 510-0293, Japan.
Abstract
OBJECTIVES: 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. METHODS: A daughter and her father immigrated to the high incident area from outside the Kii Peninsula. The father developed ALS 18 years later after immigration, and his daughter also developed ALS 65 years after immigration. They showed pure ALS phenotype without parkinsonism and dementia. RESULTS: 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. DISCUSSION: The findings in an immigrant family established that certain environmental factors play a critical role in the pathogenesis of Kii ALS/PDC.
OBJECTIVES: 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. METHODS: A daughter and her father immigrated to the high incident area from outside the Kii Peninsula. The father developed ALS 18 years later after immigration, and his daughter also developed ALS 65 years after immigration. They showed pure ALS phenotype without parkinsonism and dementia. RESULTS: 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. DISCUSSION: The findings in an immigrant family established that certain environmental factors play a critical role in the pathogenesis of Kii ALS/PDC.