Clinical and pathological studies of familial amyotrophic lateral sclerosis (FALS) with SOD1 H46R mutation in large Japanese families

Takayo Arisato, Ryuichi Okubo, Hitoshi Arata, Koji Abe, Kei Fukada, Saburo Sakoda, Akira Shimizu, Xing Hui Qin, Shuji Izumo, Mitsuhiro Osame, Masanori Nakagawa

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

We clarified the clinical and pathological aspects of familial amyotrophic lateral sclerosis (FALS) with SOD1 H46R heterozygous mutation in the Miyakonojo Basin, a region in southern Japan where the prevalence of ALS is 11.4 per 105 of the population. We studied 17 patients, including one autopsy case, in three FALS families with the mutation. The average age at disease onset in the families was 44.3±8.7 years, and the mean disease duration was 12±7.6 years, with a range of 6 to 30 years. Ten of 17 patients were unable to walk by the mean age of 56.4±12.2 years. The initial symptom was muscle weakness in the distal leg muscle in all patients. The autopsy findings of one FALS patient showed atrophy of lateral and anterior funiculi, decreased numbers of anterior horn cells, preserved posterior funiculus and absence of neuronal inclusion bodies. Percentages of mutant SOD1 protein measured by mass spectrometry were 14% in erythrocytes, 43% in the spinal cord, 47% in the iliopsoas muscle and 60% in the diaphragm. In this study, we confirmed that FALS with SOD1 H46R mutation showed uniform initial symptoms and slow disease progression with intrafamilial variation of disease severity and that inclusion body formation is not essential in FALS with this mutation.

Original languageEnglish
Pages (from-to)561-568
Number of pages8
JournalActa neuropathologica
Volume106
Issue number6
DOIs
Publication statusPublished - Dec 1 2003

Keywords

  • Autopsy case
  • Clinical course
  • FALS
  • Mutant protein
  • SOD1 H46R mutation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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