Expanding the phenotypic spectrum of SOD1‑related ALS: upper motor neuron predominance in a p.D91A case

Mutations in superoxide dismutase 1 SOD1 are the second most common genetic cause of ALS, usually associated with prevalent lower motor neuron phenotypes. We describe a 66-year-old woman with slowly progressive spastic paraparesis, initially diagnosed as primary lateral sclerosis, who carried a heterozygous p.D91A mutation. Clinical and neurophysiological findings indicated predominant upper motor neuron involvement, an unusual presentation for this mutation. This case broadens the SOD1 phenotypic spectrum and highlights the importance of early genetic testing in atypical motor syndromes, given the availability of targeted therapies where diagnostic delay may limit benefit.