Distinctive clinicopathological features of 2 large families with amyotrophic lateral sclerosis having L106V mutation in SOD1 gene

A clinicopathological study of 2 families with familial amyotrophic lateral sclerosis was previously reported [1]. The present study continues to investigate these families, with detailed clinical, genetic, and neuropathological studies performed on 24 patients, including 5 autopsy cases of the families. A point mutation at codon 106 (L106V) in the copper/zinc superoxide dismutase-1 (SOD1) gene was identified in the families. Average age at onset was 52.0 ± 9.4 years, and initial symptoms were weakness and atrophy in the distal muscles of the lower extremities in most patients. Half of the patients showed neurogenic bladder (overactive bladder) and sensory impairment. The neurophysiological study showed peripheral/central conduction delay. Neuropathological examination revealed severe motor neuron loss with many bizarre reactive astrocytes in the spinal anterior horn. SOD1-immunopositive Lewy body-like hyaline inclusions and aggregation of neurofilaments were observed in the surviving anterior horn cells. Degeneration of the corticospinal tract was relatively minor. In addition, slight but diffuse gliosis was identified in the hypothalamus and medial nucleus of thalamus. Neurogenic bladder, sensory impairment, and degeneration of the hypothalamus and thalamus might be specific features in patients with familial amyotrophic lateral sclerosis with L106V mutation in the SOD1 gene.