An autopsy case of familial amyotrophic lateral sclerosis with Gly93Ser mutation in Cu/Zn superoxide dismutase

摘要

We describe a 39-year-old Japanese woman with familial amyotrophic lateral sclerosis (FALS) in whom we identified a missense mutation (Gly93->Ser) in exon 4 of the Cu/Zn superoxidase dismutase-1 (SOD1) gene in which no pathological data have been available. The patient's aunt died of ALS at age 67. Our patient developed muscle weakness in the legs from age 23. At age 24, she also experienced weakness in the arms. At age 30, she exhibited hoarseness and dysphagia. She became bedridden from the age of 36 years. At age 38, she developed difficulty in respiration. Sixteen years after onset of the disease, at the age of 39 years, the patient died of respiratory failure. She had no clear upper motor neuron involvement. Neuropatho-logical examinations showed neuronal loss in Clarke's nucleus (Fig. 1), fiber loss in the spinocerebellar tract and the posterior column (Fig. 2), and degeneration of the dentatorubral system (Figs. 3 and 4), in addition to the degeneration of the upper and lower motor neuron systems (Fig. 5). Marked atrophy and myelin pallor were present in the superior cerebellar peduncle (Fig. 6). Our case showed severe loss of anterior horn cells, but mild changes in the corticospinal tract. However, the patient has no Lewy body-like hyaline inclusions (LBHIs), which are characteristic features of mutant SOD1-related FALS with posterior column involvement [1-5]. Degeneration of the dentatorubral system has not been reported in FALS with SOD1 mutation. Based on clinical, genetic and pathological findings with a review of the literature, we suggest that degeneration of the dentatorubral system and the absence of LBHIs in our case are pathological features in FALS with the Gly93Ser mutation.