The G41D mutation in the superoxide dismutase 1 gene is associated with slow motor neuron progression and mild cognitive impairment in a Chinese family with amyotrophic lateral sclerosis

Most patients with amyotrophic lateral sclerosis (ALS) have mild cognitive impairment.1 A familial ALS (fALS) case carrying a SOD1 missense mutation with non-executive cognitive impairment was reported.2 However, cognitive impairment in fALS remains poorly understood. We report on a Chinese family with a novel SOD1 mutation, G41D, which causes slow progression of motor neuron function loss and cognitive impairment. The research was approved by the Ethics Committee of The People's Hospital of Jiangsu Province. A 62-year-old woman (the proband) was admitted to our department due to a 12-year history of progressive limb weakness and gait impairment. We obtained informed consent for the genetic study from the patient. The proband had muscle weakness in her left upper limb at 50 years of age and subsequently developed muscle weakness in both upper limbs as well as progressive upper motor neuron symptoms in her lower extremities. At 62 years of age, her muscle weakness worsened, with the appearance of atrophy in her upper limbs and diffuse cramps in her lower limbs, including gait abnormalities. She showed dysarthria and dysphonia, and no dysphagia. Neurological examination showed diffuse weakness in the distal arm muscles with less strength than antigravity, and moderate weakness in the proximal arm muscles with strength against resistance. Fasciculation was observed in these muscles. She also exhibited tongue hypotrophy with fasciculation. Additionally, there was pathological hyperreflexia. Cerebrospinal fluid analyses were normal and serum cryoglobulins were absent. MRI scans of the brain and cervical, thoracic and lumber spine were normal. The 18F-fluorodeoxyglucose cerebral positron emission tomography revealed reduced uptake in the left supermarginal gyrus and left frontopolar …