Rinsho Shinkeigaku (Clinical Neurology)

Case Report

Clinical features and neuropathological findings of familial amyotrophic lateral sclerosis with an H43R mutation in Cu/Zn superoxide dismutase

Yoko Mochizuki, M.D.1)2), Tomohiko Mizutani, M.D.1), Ryoichi Nakano, M.D.3), Takao Fukushima, M.D.3), Taku Honma, M.D.4), Norimichi Nemoto, M.D.4) and Kazuo Takei, M.D.5)

Division of Neurology, Department of Medicine, Nihon University School of Medicine1), Department of Internal Medicine, Tokyo Metropolitan Kita Medical and Rehabilitation Center2), Department of Neurology, Clinical Neuroscience Branch, Brain Research Institute, Niigata University3), Department of Pathology, Nihon University School of Medicine4), Department of Neurology, Saitama Medical School5)

We report the clinical and neuropathological features of a Japanese family with familial amyotrophic lateral sclerosis (FALS), whose members have an amino acid substitution of histidine43 by arginine in Cu/Zn superoxide dismutase. A 58-year-old woman developed muscle weakness in the legs, and died of respiratory insufficiency 7 months after the onset of her weakness. Her family history included 7 patients with FALS over 3 generations. Their pertinent neurological abnormalities consisted primarily of lower motor neuron signs, and their clinical progression was rapid. Autopsy of our patient showed the involvement of the lower and upper motor neuron systems with Lewy body-like hyaline inclusions, in addition to degeneration in the posterior columns, Clarke's nuclei and posterior spinocerebellar tracts. The inclusions reacted with both anti-SOD1 and anti-ubiquitin antibodies. This is the first report of the neuropathological findings of FALS with this mutation.

(CLINICA NEUROL, 43: 491|495, 2003)
key words: Cu/Zn superoxide dismutase-1 (SOD1) gene, H43R, familial amyotrophic lateral sclerosis (FALS), posterior column involvement-type ALS, rapidly progressive-type

(Received: 25-Mar-03)